Complicated Open Wound Management in a Free Clinic Setting.
Wound healing is a complex and integrated process that involves several interdependent overlapping stages, including hemostasis, inflammation, proliferation, and vascularization. Cellulitis and skin abscesses are among the most common skin and soft tissue infections. Cellulitis typically involves the deeper dermis of subcutaneous fat and tends to have a more indolent course with the development of localized symptoms over a few days. Skin abscesses are described as a collection of pus within the dermis or subcutaneous space. Diabetes mellitus (DM) is the leading cause of impaired wound healing and consequently has higher rates of patients developing soft tissue infections. Diabetic patients experience decreased early inflammatory cell infiltration but increased numbers of neutrophils and macrophages. Complications include bacteremia, metastatic infection, sepsis, and toxic shock syndrome. In this case, we describe a 50-year-old Caucasian uninsured male who was referred to the Gary Burnstein Clinic (GBC) from a nearby hospital for wound management after an incision and drainage of a large back abscess and uncontrolled type 2 diabetes mellitus (T2DM). The patient presented with a large erythematous, indurated lesion with a cruciate incision that spanned from his mid-thoracic spine to the medial border of his left scapula. The wound management course required strict follow-up to the clinic every 48-72 hours for debridement and monitoring. This was complicated by the GBC's limited resources along with the volunteer nurses' and physicians' availability. To avoid the patient being lost to follow-up, shared decision-making was utilized to create a schedule that was advantageous for both the patient and the clinic. Ultimately, the patient made a full recovery without any adverse events. This case highlights the gaps in care for the medically uninsured. We also showcase the passion and dedication our medical volunteers exhibit to care for the community. The GBC provides high-quality healthcare to bridge gaps in access to care by offering broad specialist access while ensuring continuity of care.


"Experiences with disclosure of HIV-positive status to the infected child": Perspectives of healthcare providers in Dar es Salaam, Tanzania.
The specific age to which an HIV infected child can be disclosed to is stipulated to begin between ages 4 and 6 years. It has also been documented that before disclosure of HIV positive status to the infected child. Health care providers should consider children's cognitive-developmental ability. However, observation and situation analysis show that, health care providers still feel uncomfortable disclosing the HIV positive status to the infected child. The aim of the study was to explore healthcare providers' experiences in disclosure of HIV-positive status to the infected child. A qualitative study involving 20 health care providers who attend HIV-positive children was conducted in September, 2014 in Dar es Salaam, Tanzania. Participants were selected from ten HIV care and treatment clinics (CTC) by purposive sampling. An interview guide, translated into participants' national language (Kiswahili) was used during in-depth interviews. Sampling followed the principle of data saturation. The interviews focused on perspectives of health-care providers regarding their experience with paediatric HIV disclosure. Data from in-depth interviews were transcribed into text; data analysis followed qualitative content analysis. The results show how complex the process of disclosure to children living with HIV can be to healthcare providers. Confusion was noted among healthcare providers about their role and responsibility in the process of disclosing to the HIV infected child. This was reported to be largely due to unclear guidelines and lack of standardized training in paediatric HIV disclosure. Furthermore, healthcare providers were concerned about parental hesitancy to disclose early to the child due to lack of disclosure skills and fear of stigma. In order to improve the disclosure process in HIV infected children, healthcare providers recommended further standardized training on paediatric HIV disclosure with more emphasis on practical skills and inclusion of disclosure content that is age appropriate for children with HIV. The disclosure process was found to be a complex process. Perspectives regarding disclosure in children infected with HIV varied among healthcare providers in terms of their role in the process, clear national guidelines and appropriate standardized training for paediatric disclosure. Consistent with other studies, healthcare providers reported difficulties during disclosure because parents /guardians largely fear blame, social stigma, child's negative emotional reaction when disclosed to and have concerns about the child being too young and immature to understand the HIV condition. In order to prevent inconsistencies during the disclosure process, it is important to have in place clear guidelines and standardized paediatric HIV disclosure training for healthcare providers. This would help improve their skills in paediatric disclosure, leading to positive health outcomes for children infected with HIV.


NSAIDs Prescription Prevalence after a Cardiovascular Event Related Hospitalization in Medicaid Beneficiaries from Puerto Rico.
Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for pain and inflammation. NSAIDs are associated with serious adverse effects and cardiovascular (CV) risks that include myocardial infarction, stroke and heart failure. In the period of time immediately after a CV event, modification to the drug therapy regimen and lifestyle habits should be instituted to decrease morbidity and mortality. The objective of this study is to measure the prevalence of NSAIDs prescribing in the immediate 90 days after a CV-related hospitalization in Medicaid beneficiaries in Puerto Rico. Hospitalization claims were used to identify beneficiaries with a CVrelated hospitalization during the study period, and pharmacy claims were used to evaluate the occurrence of NSAIDs prescribing post-discharge. A total of 4,195 beneficiaries with at least one CV-related hospitalization were identified. Out of these beneficiaries, 774 (18.5%) had at least one pharmacy claim for an NSAID post discharge, and 401 (9.6%) had at least one pharmacy claim for an NSAID within 90 days post-discharge. The average time span between the discharge date and the first NSAID claim was 135 days. Almost 20% of all beneficiaries who were hospitalized for a CV event received an NSAID during the study period, with 10% of patients receiving it during the immediate 90 days post-discharge. It represents a major challenge for our healthcare system, as it may reflect unawareness on the impact of proved evidence in clinical decision making.


Predictors of visual functional outcome following treatment for cavernous sinus meningioma.
Cavernous sinus meningioma (CSM) can affect visual function and require expeditious treatment to prevent permanent visual loss. Authors of this retrospective study sought to determine the factors associated with visual functional outcomes in CSM patients treated with surgery, stereotactic radiosurgery (SRS), or stereotactic radiation therapy (SRT), alone or in combination. Consecutive patients with CSM who had presented at an academic tertiary care hospital from 2000 to 2018 were identified through retrospective chart review. Visual function-visual eye deficit (VED), optic disc (OD) appearance, intraocular pressure (IOP), and extraocular movement (EOM)-was assessed before and after treatment for CSM. VED with visual acuity (VA) ≤ 20/200 and visual field defect ≥ -11 dB, pale OD appearance in the ipsilateral or contralateral eye, increased ipsilateral IOP, and/or EOM restriction were defined as a poor visual functional outcome. Multivariable logistic regression was used to evaluate the associations between pretreatment visual functional assessment and posttreatment visual outcomes. The study cohort included 44 patients (73% female; median age 55 years), with a median clinical follow-up of 14 months. Ipsilateral VED improved, remained stable, or worsened, respectively, in 0%, 33.4%, and 66.6% of the patients after subtotal resection (STR) alone; in 52.6%, 31.6%, and 15.8% after STR plus radiation treatment; in 28.5%, 43.0%, and 28.5% after gross-total resection (GTR) alone; and in 56.3%, 43.7%, and 0% after radiation treatment (SRS or SRT) alone. Contralateral VED remained intact in all the patients after STR alone and those with radiation treatment (SRS or SRT) alone; however, it improved, remained stable, or worsened in 10.5%, 84.2%, and 5.3% after STR plus radiation treatment and in 43.0%, 28.5%, and 28.5% after GTR alone. EOM remained intact, fully recovered, remained stable, and worsened, respectively, in 0%, 50%, 50%, and 0% of the patients after STR alone; in 36.8%, 47.4%, 15.8%, and 0% of the patients after STR with radiation treatment; in 57.1%, 0%, 28.6%, and 14.3% of the patients after GTR alone; and in 56.2%, 37.5%, 6.3%, and 0% of the patients after radiation treatment (SRS or SRT) alone. In multivariable analyses adjusted for age, tumor volume, and treatment modality, initial ipsilateral poor VED (OR 10.1, 95% CI 1.05-97.2, p = 0.04) and initial ipsilateral pale OD appearance (OR 21.1, 95% CI 1.6-270.5, p = 0.02) were associated with poor ipsilateral VED posttreatment. Similarly, an initial pale OD appearance (OR 15.7, 95% CI 1.3-199.0, p = 0.03), initial poor VED (OR 21.7, 95% CI 1.2-398.6, p = 0.03), and a higher IOP in the ipsilateral eye (OR 55.3, 95% CI 1.7-173.9, p = 0.02) were associated with an ipsilateral pale OD appearance posttreatment. Furthermore, a higher initial ipsilateral IOP (OR 35.9, 95% CI 3.3-400.5, p = 0.004) was indicative of a higher IOP in the ipsilateral eye posttreatment. Finally, initial restricted EOM was indicative of restricted EOM posttreatment (OR 20.6, 95% CI 18.7-77.0, p = 0.02). Pretreatment visual functional assessment predicts visual outcomes in patients with CSM and can be used to identify patients at greater risk for vision loss.


The cyclopean ear: a new sense for the praying mantis.
The praying mantis, thought to be deaf, possesses a sensitive and specialized acoustic sense. Neural recordings show that the auditory system responds primarily to ultrasound between 25 and 45 kilohertz with thresholds of 55 to 60 decibels. Other insects with auditory tympana possess paired, laterally placed ears; the mantis has only a single ear that is located in the ventral midline between the metathoracic legs. Some species of mantis abruptly and dramatically alter their flight path when stimulated with ultrasonic pulses, suggesting a behavioral response to insectivorous echo-locating bats.


First Report of Diplodia seriata Causing Loquat Fruit Rot in Spain.
Spain is the second largest loquat (Eriobotrya japonica Lindl.) producer in the world, with about 40,000 t per year. 'Algerie' is the main cultivar planted in Alicante province (SE of Spain; Lat. 38.40° N, Long. 0.08° W), where more than 80% of Spanish commercial loquat plantations are located. In a survey of fruit losses at harvest, irregular brownish superficial dry spots (5 to 15 mm) located mainly near the stem end were observed on fruits from different orchards. After incubation at 20°C for 14 days, the spots on fruit expanded rapidly and turned to dark brown or black, producing black, unilocular, ostiolate, and thick-walled pycnidia. Isolation was performed by disinfecting the surface of symptomatic fruits with alcohol and aseptically cutting pieces of infected peel tissue and plating them in potato dextrose agar (PDA) dishes. The potential causal agent (isolate IVIA GCA-5) was identified in the Spanish Type Culture Collection (CECT, University of Valencia, Valencia, Spain). The fungus grew rapidly on both PDA and malt extract agar (MEA) at 26°C, covering the entire plate surface with dark gray mycelium within 4 days. The plate reverse was dark gray to black. The conidia were brown and aseptate, with the apex broadly rounded and the base rounded or truncate, and 23 × 11 μm (n = 50). The identification of Diplodia seriata De Not. was molecularly confirmed with the amplification with the primers ITS1 and ITS4 and subsequent sequencing of the internal transcribed spacer ITS1-5.8S-ITS2 region of the rDNA extracted from the isolate IVIA GCA-5 (GenBank Accession No. JX987099). Furthermore, the region D1/D2 in the 5' end of the 28S rDNA gene was amplified with the primers NL1 and NL4 and sequenced (JX997743). A nucleotide BLAST analysis showed in both cases 100% identity with D. seriata [EF127892 (3) and AY928050, respectively]. To fulfill Koch's postulates, 5-mm diameter mycelial plugs from 7-day-old colonies of isolate IVIA GCA-5 grown on PDA at 25°C were aseptically transferred to skin wounds on superficially disinfected 'Algerie' loquats (one plug per fruit; n = 9). Wounded but not inoculated fruit were used as controls. The experiment was repeated three times. Inoculated fruit developed lesions of 18 to 100 mm after 7 to 21 days of incubation at 20°C. No lesion was observed on controls. The fungus was consistently reisolated from inoculated fruit. D. seriata is a broadly spread pathogen causing cankers, blight, dieback, and fruit rots in vines and many fruit trees. In Spain, it has been reported to cause fruit rot of olive (1) and branch dieback in olive (2) and grapevine (4). To our knowledge, this is the first report worldwide of D. seriata causing loquat fruit rot. References: (1) J. Moral et al. Plant Dis. 92:311, 2008. (2) J. Moral et al. Phytopathology 100:1340, 2010. (3) A. J. L. Phillips et al. Fungal Divers. 25:141, 2007. (4) J. R. Úrbez-Torres et al. Plant Dis. 90:835, 2006.


Intergroup Contact, COVID-19 News Consumption, and the Moderating Role of Digital Media Trust on Prejudice Toward Asians in the United States: Cross-Sectional Study.
The perceived threat of a contagious virus may lead people to be distrustful of immigrants and out-groups. Since the COVID-19 outbreak, the salient politicized discourses of blaming Chinese people for spreading the virus have fueled over 2000 reports of anti-Asian racial incidents and hate crimes in the United States. The study aims to investigate the relationships between news consumption, trust, intergroup contact, and prejudicial attitudes toward Asians and Asian Americans residing in the United States during the COVID-19 pandemic. We compare how traditional news, social media use, and biased news exposure cultivate racial attitudes, and the moderating role of media use and trust on prejudice against Asians is examined. A cross-sectional study was completed in May 2020. A total of 430 US adults (mean age 36.75, SD 11.49 years; n=258, 60% male) participated in an online survey through Amazon's Mechanical Turk platform. Respondents answered questions related to traditional news exposure, social media use, perceived trust, and their top three news channels for staying informed about the novel coronavirus. In addition, intergroup contact and racial attitudes toward Asians were assessed. We performed hierarchical regression analyses to test the associations. Moderation effects were estimated using simple slopes testing with a 95% bootstrap confidence interval approach. Participants who identified as conservatives (β=.08, P=.02), had a personal infection history (β=.10, P=.004), and interacted with Asian people frequently in their daily lives (β=.46, P<.001) reported more negative attitudes toward Asians after controlling for sociodemographic variables. Relying more on traditional news media (β=.08, P=.04) and higher levels of trust in social media (β=.13, P=.007) were positively associated with prejudice against Asians. In contrast, consuming news from left-leaning outlets (β=-.15, P=.001) and neutral outlets (β=-.13, P=.003) was linked to less prejudicial attitudes toward Asians. Among those who had high trust in social media, exposure had a negative relationship with prejudice. At high levels of trust in digital websites and apps, frequent use was related to less unfavorable attitudes toward Asians. Experiencing racial prejudice among the Asian population during a challenging pandemic can cause poor psychological outcomes and exacerbate health disparities. The results suggest that conservative ideology, personal infection history, frequency of intergroup contact, traditional news exposure, and trust in social media emerge as positive predictors of prejudice against Asians and Asian Americans, whereas people who get COVID-19 news from left-leaning and balanced outlets show less prejudice. For those who have more trust in social media and digital news, frequent use of these two sources is associated with lower levels of prejudice. Our findings highlight the need to reshape traditional news discourses and use social media and mobile news apps to develop credible messages for combating racial prejudice against Asians.


Biodemographic trajectories of longevity.
Old-age survival has increased substantially since 1950. Death rates decelerate with age for insects, worms, and yeast, as well as humans. This evidence of extended postreproductive survival is puzzling. Three biodemographic insights--concerning the correlation of death rates across age, individual differences in survival chances, and induced alterations in age patterns of fertility and mortality--offer clues and suggest research on the failure of complicated systems, on new demographic equations for evolutionary theory, and on fertility-longevity interactions. Nongenetic changes account for increases in human life-spans to date. Explication of these causes and the genetic license for extended survival, as well as discovery of genes and other survival attributes affecting longevity, will lead to even longer lives.


Evidence to Action: Highlights From Transform Nutrition Research (2012-2017).
The Transform Nutrition ( Transform) research consortium (2012-2017), led by the International Food Policy Research Institute, sought to generate evidence to inform and inspire action to address undernutrition in 4 high-burden countries (India, Bangladesh, Kenya, and Ethiopia) and globally. Within the context of the literature, this synthesis article brings together core findings of Transform, highlighting priorities for future research. This article uses a narrative approach to synthesize diverse study findings that collectively address Transform's three primary research questions: (1) How can nutrition-specific interventions be appropriately designed, implemented, scaled, and sustained in different settings?; (2) How can the nutritional impact of social protection and agriculture be improved?; and (3) How can enabling environments be promoted so as to use existing political and economic resources more effectively? Highlights of Transform include (1) improved understanding of the relative effectiveness of different combinations of nutrition-specific interventions and the ways in which they can be scaled for maximal impact; (2) evidence that shows that social protection and agriculture need to be explicitly linked to nutrition in order to contribute to stunting reduction; (3) identification of key components of "enabling environments" for nutrition and how they can be cultivated/sustained; (4) research that examines ways in which leaders emerge and operate to change the political and policy landscape in different settings; and (5) "stories of change" that provide in-depth contextual knowledge of how transformative change has been driven in countries that have made inroads in reducing malnutrition. The conclusion highlights the contributions of the consortium and provides recommendations for future research.


Meta-analytic evidence for decreased heart rate variability in chronic pain implicating parasympathetic nervous system dysregulation.
Both sympathetic and parasympathetic nervous systems are involved in regulating pain states. The activity of these systems seems to become disturbed in states of chronic pain. This disruption in autonomic balance can be measured through the assessment of heart rate variability (HRV), that is, the variability of the interval between consecutive heart beats. However, there is yet to be a systematic evaluation of the body of literature concerning HRV across several chronic pain conditions. Moreover, modern meta-analytical techniques have never been used to validate and consolidate the extent to which HRV may be decreased in chronic pain. Following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement guidelines, this study systematically evaluated and critically appraised the literature concerning HRV in people living with chronic pain. After screening 17,350 sources, 51 studies evaluating HRV in a chronic pain group met the inclusion criteria. Twenty-six moderate-high quality studies were included in quantitative meta-analyses. On average, the quality of studies was moderate. There were 6 frequency-domain and time-domain measures of HRV across a broad range of chronic pain conditions. High heterogeneity aside, pooled results from the meta-analyses reflected a consistent, moderate-to-large effect of decreased high-frequency HRV in chronic pain, implicating a decrease in parasympathetic activation. These effects were heavily influenced by fibromyalgia studies. Future research would benefit from wider use of standardised definitions of measurement, and also investigating the synergistic changes in pain state and HRV throughout the development and implementation of mechanism-based treatments for chronic pain.


Prion-induced amyloid heart disease with high blood infectivity in transgenic mice.
We investigated extraneural manifestations in scrapie-infected transgenic mice expressing prion protein lacking the glycophosphatydylinositol membrane anchor. In the brain, blood, and heart, both abnormal protease-resistant prion protein (PrPres) and prion infectivity were readily detected by immunoblot and by inoculation into nontransgenic recipients. The titer of infectious scrapie in blood plasma exceeded 10(7) 50% infectious doses per milliliter. The hearts of these transgenic mice contained PrPres-positive amyloid deposits that led to myocardial stiffness and cardiac disease.


Pediatricians' attitudes, beliefs, and practices regarding clinical practice guidelines: a national survey.
Clinical practice guidelines are increasingly being used for a wide variety of medical conditions, but not enough is known about physicians' attitudes and beliefs about guidelines, how often and under what circumstances they are used, and factors associated with their acceptance. To determine practice guideline attitudes, beliefs, practices, and factors associated with use among a representative national sample of general pediatricians. Cross-sectional mail survey. Random sample of general pediatrician members of the American Academy of Pediatrics residing in all 50 states and Puerto Rico. Twenty-four multiple-choice, Likert scale, yes-no, and open-ended questions about pediatric clinical practice guidelines. From 1088 respondents, 461 specialists were excluded; the remaining 627 general pediatricians were mostly male (61%), white (81%), and in group practice (62%) in a suburban location (48%). Practice guidelines are used by 35% of pediatricians, in part by 44%, and not at all by 21%. Over 100 different practice guidelines are used, most commonly for asthma (77%), hyperbilirubinemia (27%), and otitis media (19%). Common reasons for use of practice guidelines include standardization of care (17%) and helpfulness (10%). Commonly cited problems with practice guidelines include failure to allow for clinical judgment (54%), use in litigation (16%), and limitation of autonomy (5%). In multivariate analysis, the odds of practice guideline use were greater among pediatricians in health maintenance organization practices (odds ratio [OR]: 9.1; 95% confidence interval [CI]: 1.2-68.0) and those who were nonwhite (OR: 2.3; 95% CI: 1.1-4.8), but lower in those with more weekly patient visits (OR:.7; 95% CI:.5-.9). Features most likely to lead to practice guideline use include simplicity (16%), feasibility (12%), and evidence of improved outcomes (10%). Most pediatricians agree that practice guidelines improve outcomes (89%), are motivated by a desire to improve quality (94%), and should not be used in litigation (82%) or disciplinary actions (77%), nor be motivated by a desire to reduce costs (73%). Most general pediatricians use practice guidelines, but no specific guidelines, except those for asthma, are used by >27% of pediatricians. The results of this study suggest that practice guidelines are most likely to be followed if they are simple, flexible, rigorously tested, not used punitively, and are motivated by desires to improve quality, not reduce costs.


[Histoculture drug response assay on non-small cell lung cancer].
We examined the chemosensitivity of non-small cell lung cancer (NSCLC) tissues to CDDP, 5-FU, ADM, MMC, ETP and SN38 using histoculture drug response assay (HDRA). One-hundred and thirty surgical specimens from NSCLC patients who were not given preoperative chemotherapy were used. The inhibition indexes of CDDP, 5-FU, MMC, ADM, ETP and SN38 were 39.1 +/- 18.2%, 48.0 +/- 19.7%, 63.3 +/- 17.7%, 47.6 +/- 22.0%, 36.9 +/- 21.1%, and 37.9 +/- 25.2%, respectively. Inhibition indexes were above the cutoff level, i.e., 'judged sensitive,' in 40 cases (31.3%) for CDDP, 34 cases (27.4%) for 5-FU, 54 cases (44.3%) for MMC, 36 cases (33.0%) for ADM, 29 cases (29.8%) for ETP, and 34 cases (37.4%) for SN38, respectively. In almost one-third of patients, the inhibition indexes of all drugs were under cutoff levels. Correlations between in vitro chemosensitivity data and patient responses to chemotherapy were obtained from 16 evaluable patients, and a 44.4% true positive rate and a 100% true negative rate were observed. Our results with HDRA for NSCLC showed a high incidence of intrinsic multidrug resistance. HDRA may help doctors to avoid non-effective chemotherapy for NSCLC patients.


Tributyltin partitioning in sediments: effect of aging.
The effect of aging on the solid/pore-water partitioning and desorption behaviour of tributyltin (TBT) in sediments was examined. Three sediment samples with contrasting physical and chemical properties were spiked with 10 mg/kg TBT and aged under sterile conditions for periods of time ranging from 1 to 84 days. Aging had a negligible effect on partitioning and desorption behaviour in a sandy sample with very low organic carbon content (0.2% w/w). In contrast, for samples with larger amounts of organic carbon (2.6% and 4.8% w/w), aging caused substantial increases in TBT sorption. For these samples, apparent distribution coefficients (KD,app) obtained from sequential 2 h desorption experiments also exhibited a twofold increase between spiked sediments subjected to aging for 1 day and 84 days. This study demonstrates that aging effects may be an important aspect of TBT fate in contaminated sediments.


Drosophila Ncd reveals an evolutionarily conserved powerstroke mechanism for homodimeric and heterodimeric kinesin-14s.
Drosophila melanogaster kinesin-14 Ncd cross-links parallel microtubules at the spindle poles and antiparallel microtubules within the spindle midzone to play roles in bipolar spindle assembly and proper chromosome distribution. As observed for Saccharomyces cerevisiae kinesin-14 Kar3Vik1 and Kar3Cik1, Ncd binds adjacent microtubule protofilaments in a novel microtubule binding configuration and uses an ATP-promoted powerstroke mechanism. The hypothesis tested here is that Kar3Vik1 and Kar3Cik1, as well as Ncd, use a common ATPase mechanism for force generation even though the microtubule interactions for both Ncd heads are modulated by nucleotide state. The presteady-state kinetics and computational modeling establish an ATPase mechanism for a powerstroke model of Ncd that is very similar to those determined for Kar3Vik1 and Kar3Cik1, although these heterodimers have one Kar3 catalytic motor domain and a Vik1/Cik1 partner motor homology domain whose interactions with microtubules are not modulated by nucleotide state but by strain. The results indicate that both Ncd motor heads bind the microtubule lattice; two ATP binding and hydrolysis events are required for each powerstroke; and a slow step occurs after microtubule collision and before the ATP-promoted powerstroke. Note that unlike conventional myosin-II or other processive molecular motors, Ncd requires two ATP turnovers rather than one for a single powerstroke-driven displacement or step. These results are significant because all metazoan kinesin-14s are homodimers, and the results presented show that despite their structural and functional differences, the heterodimeric and homodimeric kinesin-14s share a common evolutionary structural and mechanochemical mechanism for force generation.


The effect of renal function on changes in circulating concentrations of 1,25-dihydroxycholecalciferol after an oral dose.
1. 1,25- Dihydroxycholecalciferol [1,25-(OH)2D3] was administered orally to four normal subjects and six patients with chronic renal failure not on dialysis. The serum concentration of 1,25-(OH)2D3 was measured by radioimmunoassay in both groups from samples taken before, and at regular intervals up to 48 h after, the oral dose. 2. The plasma half-time for the disappearance of the administered 1,25-(OH)2D3 was estimated by determining the time for a 50% reduction from the peak increment of the sterol. In normal subjects the calculated value ranged from 5 to 8 h compared with 18 to 44 h in uraemic patients. 3. It appears from our studies that in uraemic subjects there is impaired ability to metabolize or excrete 1,25-(OH)2D3.


Accelerated human cardiac diffusion tensor imaging using simultaneous multislice imaging.
To demonstrate the feasibility of accelerating measurements of cardiac fiber structure using simultaneous multislice (SMS) imaging. SMS excitation with a blipped controlled aliasing (CAIPI) readout was incorporated into a diffusion-encoded stimulated echo pulse sequence to obtain diffusion measurements in three separate slices of the heart (8-mm thickness, 12-mm gap). A novel image entropy-based method for removing image ghosts in blipped CAIPI acquisitions is also introduced that enables SMS imaging of closely spaced slices in the heart. The average retained signal-to-noise ratio (SNR) using this acquisition scheme is 70% ± 5%, higher than the standard 1/3 = 57% SNR penalty with three-fold acceleration. No significant difference was observed in the apparent diffusion coefficient and helix angle diffusion parameters between a time-equivalent conventional single-slice scan and the three-fold accelerated SMS acquisition. A 10% mean bias was observed in fractional anisotropy between single-slice and SMS acquisitions. The new sequence was used to obtain high-quality diffusion measurements in three closely spaced cardiac slices in a clinically feasible nine breath-hold examination. The accelerated multiband sequence is anticipated to improve quantitative measurements of cardiac microstructure by reducing the number of breath-holds required for the scan, making it practical to incorporate diffusion tensor measurements within a comprehensive clinical examination.


Cardiovascular Risk and Cognitive Function in Middle-Aged and Older Hispanics/Latinos: Results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).
Cardiovascular disease is linked to cognitive decline and disorders (e.g., dementia). The evidence is based largely on older non-Latino White cohorts. Examine the association between global vascular risk and cognitive function among Hispanics/Latinos in the United States. We used data from a large sample of stroke- and cardiovascular disease-free, middle-aged and older Hispanics/Latinos with diverse backgrounds (n=7,650) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). We compared associations between two measures of cardiovascular risk (CVR), the Framingham Cardiovascular Risk Score (FCRS) and the multiethnic Global Vascular Risk Score (GVRS), and cognitive performance using measures of global and domain specific cognitive function, and tested for modification by sex and age. Higher FCRS and GVRS were associated with lower global cognition and higher probability of low mental status, after covariates adjustment. Both CVR indices were associated with lower performances in learning and memory, verbal fluency, and psychomotor speed. Higher GVRS presented stronger associations with lower cognitive function compared to the FCRS. Women and younger age (45-64 years) exhibited more pronounced associations between higher CVR and worse cognition, particularly so with the GVRS. CVR is also a risk for compromised cognitive function and evident in middle-age among Hispanics/Latinos. The multiethnic GVRS, tailored to specific risks based on racial/ethnic background, is feasible to use in primary care settings and can provide important insight on cognitive risk. Even modest shifts in population toward cardiovascular health in the high-risk Hispanic/Latino population can have important positive impacts on healthy cognitive aging.


Visualization of the Serratia Type VI Secretion System Reveals Unprovoked Attacks and Dynamic Assembly.
The Type VI secretion system (T6SS) is a bacterial nanomachine that fires toxic proteins into target cells. Deployment of the T6SS represents an efficient and widespread means by which bacteria attack competitors or interact with host organisms and may be triggered by contact from an attacking neighbor cell as a defensive strategy. Here, we use the opportunist pathogen Serratia marcescens and functional fluorescent fusions of key components of the T6SS to observe different subassemblies of the machinery simultaneously and on multiple timescales in vivo. We report that the localization and dynamic behavior of each of the components examined is distinct, revealing a multi-stage and dynamic assembly process for the T6SS machinery. We also show that the T6SS can assemble and fire without needing a cell contact trigger, defining an aggressive strategy that broadens target range and suggesting that activation of the T6SS is tailored to survival in specific niches.


Symmetry-breaking in mammalian cell cohort migration during tissue pattern formation: role of random-walk persistence.
Coordinated, cohort cell migration plays an important role in the morphogenesis of tissue patterns in metazoa. However, individual cells intrinsically move in a random walk-like fashion when studied in vitro. Hence, in the absence of an external orchestrating influence or template, the emergence of cohort cell migration must involve a symmetry-breaking event. To study this process, we used a novel experimental system in which multiple capillary endothelial cells exhibit spontaneous and robust cohort migration in the absence of chemical gradients when cultured on micrometer-scale extracellular matrix islands fabricated using microcontact printing. A computational model suggested that directional persistence of random-walk and dynamic mechanical coupling of adjacent cells are the critical control parameters for this symmetry-breaking behavior that is induced in spatially-constrained cell ensembles. The model predicted our finding that fibroblasts, which exhibit a much shorter motility persistence time than endothelial cells, failed to undergo symmetry breaking or produce cohort migration on the matrix islands. These findings suggest that cells have intrinsic motility characteristics that are tuned to match their role in tissue patterning. Our results underscore the importance of studying cell motility in the context of cell populations, and the need to address emergent features in multicellular organisms that arise not only from cell-cell and cell-matrix interactions, but also from properties that are intrinsic to individual cells.


Resveratrol reduces liver endoplasmic reticulum stress and improves insulin sensitivity in vivo and in vitro.
Purpose: The aim of the study was to examine the effects of resveratrol upon hepatic endoplasmic reticulum stress (ERS) and insulin sensitivity in vivo and in vitro. Material and methods: C57BL/6J mice were fed a high-fat diet (HFD) for 8 weeks, and insulin resistance was evaluated by the intraperitoneal glucose tolerance test (IPGTT). Mice were then treated with resveratrol for 12 weeks and blood and liver samples collected. Blood biochemical indicators were determined by kits, liver protein expression was determined by western blot, and morphological changes were observed by histological staining. Palmitic acid (PA)-induced insulin-resistant HepG2 cells were established. Cells were exposed to 100, 50 or 20 μM resveratrol for 24 hrs, and proliferation/cytotoxicity was determined. Cells were divided into five groups: control, PA, PA + Rev (100 μM), PA + Rev (50 μM) and PA + Rev (20 μM) groups. After 24 hrs of treatment, cellular proteins were analyzed the same way as animal tissues. Results: The IPGTT confirmed that the insulin resistance model was established successfully. After resveratrol treatment, fasting blood glucose and cholesterol levels declined and the quantitative insulin sensitivity check index increased. Western-blot results showed that resveratrol-treated HFD mice had reduced hepatic levels of p-PERK, ATF-4 and TRIB3, and increased the levels of ATF-6, p-AKT and p-GSK3β. In the cell model, resveratrol with 100 and 50 μM enhanced ERS and insulin resistance, whereas 20 μM had beneficial effects, similar to the animal model. Conclusion: Resveratrol reduced hepatic ERS, thereby improving insulin sensitivity and glucose levels. However, high doses of resveratrol had harmful effects on cells, elevating ERS and insulin resistance. The safe dose of resveratrol needs further investigation.


Patients with hippocampal amnesia cannot imagine new experiences.
Amnesic patients have a well established deficit in remembering their past experiences. Surprisingly, however, the question as to whether such patients can imagine new experiences has not been formally addressed to our knowledge. We tested whether a group of amnesic patients with primary damage to the hippocampus bilaterally could construct new imagined experiences in response to short verbal cues that outlined a range of simple commonplace scenarios. Our results revealed that patients were markedly impaired relative to matched control subjects at imagining new experiences. Moreover, we identified a possible source for this deficit. The patients' imagined experiences lacked spatial coherence, consisting instead of fragmented images in the absence of a holistic representation of the environmental setting. The hippocampus, therefore, may make a critical contribution to the creation of new experiences by providing the spatial context into which the disparate elements of an experience can be bound. Given how closely imagined experiences match episodic memories, the absence of this function mediated by the hippocampus, may also fundamentally affect the ability to vividly re-experience the past.


A proteomic screen reveals SCFGrr1 targets that regulate the glycolytic-gluconeogenic switch.
Entry into the cell cycle is regulated by nutrient availability such that cells do not divide when resources are limited. The Skp1-Cul1-F-box (SCF) ubiquitin ligase with the F-box protein Grr1 (SCF(Grr1)) controls the proteolytic turnover of regulators of cell-cycle entry and a glucose sensor, suggesting that it links the cell cycle with nutrient availability. Here, we show that SCF(Grr1) broadly regulates cellular metabolism. We have developed a proteomic screening method that uses high-throughput quantitative microscopy to comprehensively screen for ubiquitin-ligase substrates. Seven new metabolic targets of SCF(Grr1) were identified, including two regulators of glycolysis--the transcription factor Tye7 and Pfk27. The latter produces the second messenger fructose-2,6-bisphosphate that activates glycolysis and inhibits gluconeogenesis. We show that SCF(Grr1) targets Pfk27 and Tye7 in response to glucose removal. Moreover, Pfk27 is phosphorylated by the kinase Snf1, and unphosphorylatable Pfk27 is stable and inhibits growth in the absence of glucose. These results demonstrate a role for SCF(Grr1) in regulating the glycolytic-gluconeogenic switch.


Allergic airway inflammation disrupts interleukin-17 mediated host defense against streptococcus pneumoniae infection.
Despite decreasing rates of invasive pneumococcal disease caused by vaccine serotypes, the prevalence of invasive pneumococcal pneumonia in asthmatic patients remains high. However, little is known about the mechanisms underlying the susceptibility of the asthmatic airway to bacterial infections. In this study, we used a combined model of allergic airway inflammation and Streptococcus pneumoniae lung infection to investigate the association between persistent allergic inflammation in the airway and antibacterial host defenses against S. pneumoniae. When challenged with S. pneumoniae, allergic mice exhibited higher airway bacterial burdens, greater eosinophil infiltration, lower neutrophil infiltration, and more severe structural damage than non-allergic mice. In sensitized mice, S. pneumoniae infection elicited higher IL-4 but lower IFN-γ, IL-17 and defensin-β2 expression than in control mice. These results indicate that persistent allergic inflammation impaired airway host defense against S. pneumoniae is associated with the insufficient IL-17 responses. To elicit IL-17 induced-anti-bacterial immune responses, mice were intranasally immunized with rIL-17. Immunized mice exhibited fewer bacterial colonies in the respiratory tract and less severe lung pathology than unimmunized mice. rIL-17 contributed to airway host defense enhancement and innate immune response promotion, which was associated with increased IL-23, MIP-2 and defensin-β2 expression. Administration of exogenous IL-17 (2 μg/mouse) suppressed eosinophil-related immune responses. The results demonstrate IL-17 plays a key role in host defenses against bacterial infection in allergic airways and suggest that exogenous IL-17 administration promotes the anti-becterial immune responses and attenuates the existed allergic inflammation.


Metabolic rate and membrane fatty acid composition in birds: a comparison between long-living parrots and short-living fowl.
Both basal metabolic rate (BMR) and maximum lifespan potential (MLSP) vary with body size in mammals and birds and it has been suggested that these are mediated through size-related variation in membrane fatty acid composition. Whereas the physical properties of membrane fatty acids affect the activity of membrane proteins and, indirectly, an animal's BMR, it is the susceptibility of those fatty acids to peroxidation which influence MLSP. Although there is a correlation between body size and MLSP, there is considerable MLSP variation independent of body size. For example, among bird families, Galliformes (fowl) are relatively short-living and Psittaciformes (parrots) are unusually long-living, with some parrot species reaching maximum lifespans of more than 100 years. We determined BMR and tissue phospholipid fatty acid composition in seven tissues from three species of parrots with an average MLSP of 27 years and from two species of quails with an average MLSP of 5.5 years. We also characterised mitochondrial phospholipids in two of these tissues. Neither BMR nor membrane susceptibility to peroxidation corresponded with differences in MLSP among the birds we measured. We did find that (1) all birds had lower n-3 polyunsaturated fatty acid content in mitochondrial membranes compared to those of the corresponding tissue, and that (2) irrespective of reliance on flight for locomotion, both pectoral and leg muscle had an almost identical membrane fatty acid composition in all birds.


Analysis of the developing neural system using an in vitro model by Raman spectroscopy.
We developed an in vitro model of early neural cell development. The maturation of a normal neural cell was studied in vitro using Raman spectroscopy for 120 days. The Raman spectra datasets were analyzed by principal component analysis (PCA) to investigate the relationship between maturation stages and molecular composition changes in neural cells. According to the PCA, the Raman spectra datasets can be classified into four larger groups. Previous electrophysiological studies have suggested that a normal neural cell goes through three maturation states. The groups we observed by Raman analysis showed good agreement with the electrophysiological results, except with the addition of a fourth state. The results demonstrated that Raman analysis was powerful to investigate the daily changes in molecular composition of the growing neural cell. This in vitro model system may be useful for future studies of the effects of endocrine disrupters in the developing early neural system.


An examination of genetic diversity and effective population size in Atlantic salmon populations.
Effective population size (Ne) is an important parameter in the conservation of genetic diversity. Comparative studies of empirical data that gauge the relative accuracy of Ne methods are limited, and a better understanding of the limitations and potential of Ne estimators is needed. This paper investigates genetic diversity and Ne in four populations of wild anadromous Atlantic salmon (Salmo salar L.) in Europe, from the Rivers Oir and Scorff (France) and Spey and Shin (Scotland). We aimed to understand present diversity and historical processes influencing current population structure. Our results showed high genetic diversity for all populations studied, despite their wide range of current effective sizes. To improve understanding of high genetic diversity observed in the populations with low effective size, we developed a model predicting present diversity as a function of past demographic history. This suggested that high genetic diversity could be explained by a bottleneck occurring within recent centuries rather than by gene flow. Previous studies have demonstrated the efficiency of coalescence models to estimate Ne. Using nine subsets from 37 microsatellite DNA markers from the four salmon populations, we compared three coalescence estimators based on single and dual samples. Comparing Ne estimates confirmed the efficiency of increasing the number and variability of microsatellite markers. This efficiency was more accentuated for the smaller populations. Analysis with low numbers of neutral markers revealed uneven distributions of allelic frequencies and overestimated short-term Ne. In addition, we found evidence of artificial stock enhancement using native and non-native origin. We propose estimates of Ne for the four populations, and their applications for salmon conservation and management are discussed.


Curcumin and chronic kidney disease (CKD): major mode of action through stimulating endogenous intestinal alkaline phosphatase.
Curcumin, an active ingredient in the traditional herbal remedy and dietary spice turmeric (Curcuma longa), has significant anti-inflammatory properties. Chronic kidney disease (CKD), an inflammatory disease, can lead to end stage renal disease resulting in dialysis and transplant. Furthermore, it is frequently associated with other inflammatory disease such as diabetes and cardiovascular disorders. This review will focus on the clinically relevant inflammatory molecules that play a role in CKD and associated diseases. Various enzymes, transcription factors, growth factors modulate production and action of inflammatory molecules; curcumin can blunt the generation and action of these inflammatory molecules and ameliorate CKD as well as associated inflammatory disorders. Recent studies have shown that increased intestinal permeability results in the leakage of pro-inflammatory molecules (cytokines and lipopolysaccharides) from gut into the circulation in diseases such as CKD, diabetes and atherosclerosis. This change in intestinal permeability is due to decreased expression of tight junction proteins and intestinal alkaline phosphatase (IAP). Curcumin increases the expression of IAP and tight junction proteins and corrects gut permeability. This action reduces the levels of circulatory inflammatory biomolecules. This effect of curcumin on intestine can explain why, despite poor bioavailability, curcumin has potential anti-inflammatory effects in vivo and beneficial effects on CKD.


Turnip vein-clearing virus, from pathogen to host expression profile.
SUMMARY Taxonomy: Turnip vein-clearing virus (TVCV) is a member of subgroup 3 of the Tobamovirus genus and is thus a member of the alphavirus-like supergroup of positive sense RNA-containing viruses. Physical properties: Virions, typical of tobamoviruses, are rod-shaped and consist of a single species of four-helix bundle capsid proteins of 17 kDa helically arranged around a 6.3 knt RNA which accounts for 5% of the virion mass. Virions are stable for years. Hosts: Members of the crucifer family are excellent hosts. Particularly noteworthy is that hosts include the model plant for molecular genetics, Arabidopsis thaliana. No non-mechanical vectors of transmission are known.


Genetically-barcoded SIV facilitates enumeration of rebound variants and estimation of reactivation rates in nonhuman primates following interruption of suppressive antiretroviral therapy.
HIV and SIV infection dynamics are commonly investigated by measuring plasma viral loads. However, this total viral load value represents the sum of many individual infection events, which are difficult to independently track using conventional sequencing approaches. To overcome this challenge, we generated a genetically tagged virus stock (SIVmac239M) with a 34-base genetic barcode inserted between the vpx and vpr accessory genes of the infectious molecular clone SIVmac239. Next-generation sequencing of the virus stock identified at least 9,336 individual barcodes, or clonotypes, with an average genetic distance of 7 bases between any two barcodes. In vitro infection of rhesus CD4+ T cells and in vivo infection of rhesus macaques revealed levels of viral replication of SIVmac239M comparable to parental SIVmac239. After intravenous inoculation of 2.2x105 infectious units of SIVmac239M, an average of 1,247 barcodes were identified during acute infection in 26 infected rhesus macaques. Of the barcodes identified in the stock, at least 85.6% actively replicated in at least one animal, and on average each barcode was found in 5 monkeys. Four infected animals were treated with combination antiretroviral therapy (cART) for 82 days starting on day 6 post-infection (study 1). Plasma viremia was reduced from >106 to <15 vRNA copies/mL by the time treatment was interrupted. Virus rapidly rebounded following treatment interruption and between 87 and 136 distinct clonotypes were detected in plasma at peak rebound viremia. This study confirmed that SIVmac239M viremia could be successfully curtailed with cART, and that upon cART discontinuation, rebounding viral variants could be identified and quantified. An additional 6 animals infected with SIVmac239M were treated with cART beginning on day 4 post-infection for 305, 374, or 482 days (study 2). Upon treatment interruption, between 4 and 8 distinct viral clonotypes were detected in each animal at peak rebound viremia. The relative proportions of the rebounding viral clonotypes, spanning a range of 5 logs, were largely preserved over time for each animal. The viral growth rate during recrudescence and the relative abundance of each rebounding clonotype were used to estimate the average frequency of reactivation per animal. Using these parameters, reactivation frequencies were calculated and ranged from 0.33-0.70 events per day, likely representing reactivation from long-lived latently infected cells. The use of SIVmac239M therefore provides a powerful tool to investigate SIV latency and the frequency of viral reactivation after treatment interruption.


Structural variation analysis with strobe reads.
Structural variation including deletions, duplications and rearrangements of DNA sequence are an important contributor to genome variation in many organisms. In human, many structural variants are found in complex and highly repetitive regions of the genome making their identification difficult. A new sequencing technology called strobe sequencing generates strobe reads containing multiple subreads from a single contiguous fragment of DNA. Strobe reads thus generalize the concept of paired reads, or mate pairs, that have been routinely used for structural variant detection. Strobe sequencing holds promise for unraveling complex variants that have been difficult to characterize with current sequencing technologies. We introduce an algorithm for identification of structural variants using strobe sequencing data. We consider strobe reads from a test genome that have multiple possible alignments to a reference genome due to sequencing errors and/or repetitive sequences in the reference. We formulate the combinatorial optimization problem of finding the minimum number of structural variants in the test genome that are consistent with these alignments. We solve this problem using an integer linear program. Using simulated strobe sequencing data, we show that our algorithm has better sensitivity and specificity than paired read approaches for structural variation identification. email@example.com


Compact and Low-Power Neural Spike Compression Using Undercomplete Autoencoders.
Implantable microsystems that collect and transmit neural data are becoming very useful entities in the field of neuroscience. Limited by high data rates, on-chip compression is often required to transmit the recorded data without causing power dissipation at levels that would damage sensitive brain tissue. This paper presents a data compression system designed for brain-computer interfaces (BCIs) based on undercomplete autoencoders. To the best of our knowledge, the proposed system is the first to achieve an average spike reconstruction quality of 14-dB signal-to-noise-and-distortion ratio (SNDR) at a 32× compression ratio (CR), 18-dB SNDR at a 16× CR, 22-dB SNDR at an 8× CR, and 35-dB SNDR at a 4× CR of neural spikes. The spike detection and autoencoder-based compression modules are designed and implemented in a standard 45-nm CMOS process. The post-synthesis simulation results report that the compression module consumes between 1.4 and 222.5 [Formula: see text] of power per channel and takes between 0.018 and 0.082mm2 of silicon area, depending on the desired CR and number of channels.


Prognostic significance of the lymphocyte-to-monocyte ratio in patients with malignant pleural mesothelioma.
Chronic inflammation plays a key role in the pathogenesis of malignant pleural mesothelioma (MPM) as a result of asbestos exposure. Several inflammation-based prognostic scores including the lymphocyte-to-monocyte ratio (LMR), Glasgow Prognostic Score (GPS), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) reportedly predict survival in many malignancies, while the role of LMR in MPM remains unclear. The aim of this study was to evaluate the clinical value of LMR and to compare the prognostic value of these inflammation-based scores in predicting overall survival (OS) in MPM. One hundred and fifty patients with histologically proven MPM were included in this retrospective study. Kaplan-Meier curves and multivariate Cox-regression analyses were calculated for OS. The area under the receiver operating characteristics curve (AUC) was calculated to compare the discriminatory ability of each scoring system. An elevated LMR was significantly associated with prolonged OS. Patients with LMR <2.74 had significantly poor survival compared with LMR ≥2.74 (median, 5.0 versus 14.0 months; p=0.000). The LMR consistently had a higher AUC value at 6 months (0.722), 12 months (0.712), and 24 months (0.670), compared with other scores. Multivariate analysis showed that the LMR was independently associated with OS. The LMR is an independent prognostic marker for OS in patients with MPM and is superior to other inflammation-based prognostic scores with respect to prognostic ability.


Case Study: Safety Assessment of Plant Layout between Ethylene Storage Tanks and Process Equipment According to Capacity and Weather Conditions.
In a chemical plant, even if an explosion occurs in a storage tank that handles flammable materials, the minimum separation distance is applied in a way to prevent chain explosion. This is because when an explosion occurs in a storage tank, thermal radiation affects nearby process equipment and causes a chain explosion. The separation distance between storage tanks and process equipment in a chemical plant depends on the global engineering guidelines PIP (Process Industry Practice) PNE00003 and GAPS (Global Asset Protection Services) GAP.2.5.2. However, there is a limitation in the global engineering guidelines that provide only a consistent separation distance according to the item types without considering the storage capacity and climatic conditions around the storage tank. This study analyzed the distance of thermal radiation (up to 37.5 kW/m2) according to the capacity of ethylene storage tank and climatic conditions by utilizing the Phast (DNV GL), which is widely used as a tool for quantitative risk analysis. The accident scenario was applied using the U.S. EPA (Environment Protection Agency)'s worst leakage accident scenario, considering climate variables, air temperature, wind speed, and atmospheric stability. In the simulation, atmospheric stability did not affect the radius of thermal radiation. Moreover, the thermal radiation tended to increase with increase in wind speed in the ambient condition and winter, but not in summer. Because both PIP PNE00003 and GAP.2.5.2 yield consistent separation distances without considering storage capacity and weather conditions, quantitative risk analysis of the results of thermal radiation is necessary to ensure safety.


Imaging workflow and calibration for CT-guided time-domain fluorescence tomography.
In this study, several key optimization steps are outlined for a non-contact, time-correlated single photon counting small animal optical tomography system, using simultaneous collection of both fluorescence and transmittance data. The system is presented for time-domain image reconstruction in vivo, illustrating the sensitivity from single photon counting and the calibration steps needed to accurately process the data. In particular, laser time- and amplitude-referencing, detector and filter calibrations, and collection of a suitable instrument response function are all presented in the context of time-domain fluorescence tomography and a fully automated workflow is described. Preliminary phantom time-domain reconstructed images demonstrate the fidelity of the workflow for fluorescence tomography based on signal from multiple time gates.


IgE Epitope Mapping Using Peptide Microarray Immunoassay.
IgE epitope mapping has the potential to become an additional tool for food allergy diagnosis/prognosis and to lead to a better understanding of the pathogenesis and tolerance induction of food allergy. Due to its ability to screen thousands of targets in parallel using small volumes of sample, peptide microarray has greatly facilitated large-scale IgE epitope mapping. In the past 10 years, we have developed and optimized a reliable and sensitive peptide microarray immunoassay, which has been successfully applied for IgE epitope mapping of many food allergens in our lab. Here, we describe the method of performing the peptide microarray immunoassay for IgE epitope mapping. In addition, we have upgraded the microarray platform to measure antibody affinity by adding one additional competition step, which is also described in this chapter.


Pharmacometabolomics Informs Viromics toward Precision Medicine.
Nowadays, we are experiencing the big data era with the emerging challenge of single data interpretation. Although the advent of high-throughput technologies as well as chemo- and bio-informatics tools presents pan-omics data as the way forward to precision medicine, personalized health care and tailored-made therapeutics can be only envisaged when interindividual variability in response to/toxicity of xenobiotics can be interpreted and thus, predicted. We know that such variability is the net outcome of genetics (host and microbiota) and environmental factors (diet, lifestyle, polypharmacy, and microbiota) and for this, tremendous efforts have been made to clarify key-molecules from correlation to causality to clinical significance. Herein, we focus on the host-microbiome interplay and its direct and indirect impact on efficacy and toxicity of xenobiotics and we inevitably wonder about the role of viruses, as the least acknowledged ones. We present the emerging discipline of pharmacometabolomics-informed viromics, in which pre-dose metabotypes can assist modeling and prediction of interindividual response to/toxicity of xenobiotics. Such features, either alone or in combination with host genetics, can power biomarker discovery so long as the features are variable among patients, stable enough to be of predictive value, and better than pre-existing tools for predicting therapeutic efficacy/toxicity.


The electrophysiological effect of cannabidiol on hERG current and in guinea-pig and rabbit cardiac preparations.
Cannabis use is associated with cardiovascular adverse effects ranging from arrhythmias to sudden cardiac death. The exact mechanism of action behind these activities is unknown. The aim of our work was to study the effect of cannabidiol (CBD), tetrahydrocannabinol and 11-nor-9-carboxy-tetrahydrocannabinol on cellular cardiac electrophysiological properties including ECG parameters, action potentials, hERG and IKr ion channels in HEK cell line and in rabbit and guinea pig cardiac preparations. CBD increased action potential duration in rabbit and guinea pig right ventricular papillary muscle at lower concentrations (1 µM, 2.5 µM and 5 µM) but did not significantly change it at 10 µM. CBD at high concentration (10 µM) decreased inward late sodium and L-type calcium currents as well. CBD inhibited hERG potassium channels with an IC50 value of 2.07 µM at room temperature and delayed rectifier potassium current with 6.5 µM at 37 °C, respectively. The frequency corrected QT interval (QTc) was significantly lengthened in anaesthetized guinea pig without significantly changing other ECG parameters. Although the IC50 value of CBD was higher than literary Cmax values after CBD smoking and oral intake, our results raise the possibility that hERG and potassium channel inhibition might have a role in the possible proarrhythmic adverse effects of cannabinoids in situations where metabolism of CBD impaired and/or the repolarization reserve is weakened.


Prenatal Exposure to Curcumin Protects Rod Photoreceptors in a Transgenic Pro23His Swine Model of Retinitis Pigmentosa.
Rhodopsin localization and rod photoreceptor (PR) morphology is altered in embryonic transgenic (Tg) Pro23His (P23H) miniswine. At birth, the Tg P23H swine retina lacks rod driven signaling. Curcumin, a neuroprotective food additive, has been shown to rescue Tg P23H rat rod PRs and promote normal trafficking of rhodopsin. We tested the hypothesis that prenatal exposure to curcumin would prevent PR morphological changes in Tg P23H miniswine retinae. A domestic sow was inseminated with semen from a Tg P23H miniswine founder. Her daily diet was supplemented with curcumin (100 mg/Kg body weight) from embryonic (E) day 80 to E112. The same diet without curcumin was fed to a second inseminated control sow. At E112, 2 days before parturition, both sows were euthanized. Their embryos were harvested, genotyped, and their eyes enucleated and prepared for morphological evaluation. In all pigs, we measured mean outer retinal thickness, localization of rhodopsin, and rod PR morphology. Curcumin-treated Tg P23H swine embryonic retinas were similar to WT. Untreated Tg P23H embryonic retinas show significant degenerative effects; their outer retina was thinner, rod PR morphology was abnormal, and rhodopsin was mislocalized to the outer nuclear layer (ONL). These data support a role for curcumin as a neuroprotective agent that prevents/delays morphological abnormalities associated with rod PR degeneration in this Tg P23H swine model of retinitis pigmentosa (RP). Curcumin, a Food and Drug Administration-approved dietary supplement, may arrest/delay PR degeneration if ingested by individuals at risk for developing RP.


Qatar biomedical and cancer publications in PubMed between 2000 and 2012.
The aim of this work was to analyse the past trends of biomedical and cancer publications from Qatar listed on PubMed for the years 2000-2012. These findings were then compared with the corresponding global number of publications. PubMed was searched for cancer publications, clinical trials, publications on humans or other species. Searching for "Qatar*" in the "Affiliation" field yielded the lowest number of publications; searching for "Qatar*" in the "Affiliation" or in "Title/Abstract" yielded a moderate number of results and searching for "Qatar*" in the "Affiliation" or "Title/Abstract" or "Text Word" fields yielded the highest number of publications. The annual percentage change (APC) from one year to the next was calculated for the population and each type of publication. Information on the population of Qatar was gathered from the website of Qatar Statistics Authority to determine the correlation of papers published per 1000 population. The number of publications retrieved from PubMed was not particularly different for each variation of search carried out. However, the most representative number of publications was retrieved upon searching for "Qatar*" in the "Affiliation" or in "Title/Abstract" fields. Between the years 2000 and 2012, the total number of biomedical publications from Qatar increased 24 times with an average APC of 33.4%, which was found to be more than the APC of the population in Qatar which averaged at 9%. The number of biomedical publications per 1000 population increased from 0.02 in 2000 to 0.15% in 2012. Most publications retrieved were humans studies and occasionally were for other animal species. Cancer publications in Qatar represented 16.9% of the total publications and the number of cancer publications per 1000 population increased from 0% in 2000 to 0.02% in 2012. Publications classified as clinical trials represented 4.6% of Qatar biomedical publications. Publication of cancer clinical trials were very rare (0.4%). Despite the obvious increase in Qatar biomedical and cancer publications in PubMed, the absolute numbers were relatively small. While strategies are in place, leaders of Qatar biomedical research need to consider increasing cancer research and clinical trials to meet the country's needs. Linking research output to researchers, research facilities and research funding is needed.


A budget impact analysis of rapid human immunodeficiency virus screening in Veterans Administration emergency departments.
Human immunodeficiency virus (HIV) screening is cost-effective and recommended in populations with low disease prevalence. However, because screening is not cost-saving, its financial feasibility must be understood. We forecast the costs of two Emergency Department-based HIV testing programs in the Veterans Administration: 1) implementing a non-targeted screening program and providing treatment for all patients thusly identified (Rapid Testing); and 2) treating patients identified due to late-stage symptoms (Usual Care); to determine which program was the most financially feasible. Using a dynamic decision-analysis model, we estimated the financial impact of each program over a 7-year period. Costs were driven by patient disease-severity at diagnosis, measured by CD4+ category, and the proportion of patients in each disease-severity category. Cost per CD4+ category was modeled from chart review and database analysis of treatment-naïve HIV-positive patients. Distributions of CD4+ counts differed in patients across the Rapid Testing and Usual Care arms. A non-targeted Rapid Testing program was not significantly more costly than Usual Care. Although Rapid Testing had substantial screening costs, they were offset by lower inpatient expenses associated with earlier identification of disease. Assuming an HIV prevalence of 1% and 80% test acceptance, the cost of Rapid Testing was $1,418,088, vs. $1,320,338 for Usual Care (p=0.5854). Results support implementation of non-targeted rapid HIV screening in integrated systems. This analysis adds a new component of support for HIV screening by demonstrating that rapid, non-targeted testing does not cost significantly more than a diagnostic testing approach.


Quantifying aggregated uncertainty in Plasmodium falciparum malaria prevalence and populations at risk via efficient space-time geostatistical joint simulation.
Risk maps estimating the spatial distribution of infectious diseases are required to guide public health policy from local to global scales. The advent of model-based geostatistics (MBG) has allowed these maps to be generated in a formal statistical framework, providing robust metrics of map uncertainty that enhances their utility for decision-makers. In many settings, decision-makers require spatially aggregated measures over large regions such as the mean prevalence within a country or administrative region, or national populations living under different levels of risk. Existing MBG mapping approaches provide suitable metrics of local uncertainty--the fidelity of predictions at each mapped pixel--but have not been adapted for measuring uncertainty over large areas, due largely to a series of fundamental computational constraints. Here the authors present a new efficient approximating algorithm that can generate for the first time the necessary joint simulation of prevalence values across the very large prediction spaces needed for global scale mapping. This new approach is implemented in conjunction with an established model for P. falciparum allowing robust estimates of mean prevalence at any specified level of spatial aggregation. The model is used to provide estimates of national populations at risk under three policy-relevant prevalence thresholds, along with accompanying model-based measures of uncertainty. By overcoming previously unchallenged computational barriers, this study illustrates how MBG approaches, already at the forefront of infectious disease mapping, can be extended to provide large-scale aggregate measures appropriate for decision-makers.


Optical absorption characteristics of nanometer and submicron a-Si:H solar cells with two kinds of nano textures.
The optical absorption properties of a-Si:H have acquired much attention in solar cell(SC) research. In this paper, we studied enhancement of light absorption in the a-Si:H(10%H) SCs with thicknesses from 31.25nm to 2μm and with nano textures of the column-shaped nanohole (CLNH) array and of the cone-shaped nanohole (CNNH) array, via the Finite Difference Time Domain (FDTD) simulation. For a given type of nano texture and film thickness, d, the ultimate efficiency, the ideal efficiency without considering carrier combinations, is optimized over array period, p, and filling fraction, f, and is defined as the optimized ultimate efficiency, η(0). The simulation results demonstrated that: even for the CLNH textured a-Si:H(10%H) SCs as thin as 62.5 nm,η(0) is 19.7%. When the a-Si:H(10%H) SC is thinner than a critical depth of about 250nm, the CLNH texture is more efficient than the CNNH texture, and vice versa. When the thicknesses of SCs are very thin, especially smaller than 100nm, the efficiencies of the a-Si:H(10%H) SCs are evidently higher than those of the c-Si SCs. For example, in the CLNH arrays, when d = 62.5nm, η(0)for the a-Si:H(10%H) SCs is higher than the c-Si SCs by a factor of approximate 2.3.


The efficacy and safety of fentanyl for the management of severe procedural pain in patients with burn injuries.
Fentanyl has been shown to be effective for the management of intense pain of short duration. We have recently used intravenous fentanyl for burn wound procedures because of its rapid onset, high potency, and short duration. In this report, we reviewed our experience with fentanyl in a variety of procedural burn pain settings to develop specific recommendations about its effectiveness and safety for the treatment of pain in patients with burn injuries. The medical records of patients with burn injuries who received fentanyl for wound procedures over a 2-year period were retrospectively reviewed. Patient demographics, the amount of fentanyl administered, the level of analgesia achieved, and the incidence of adverse effects were analyzed. Fifty-five patients who were 9 months to 75 years old with burn wounds (range, 1%-90% of total body surface area) received 148 doses of fentanyl for the treatment of procedural pain. An average of 8.0 +/- 7.0 microg/kg of fentanyl (range, 0.7 to 38.0 microg/kg) was required for the first wound procedure with fentanyl. No correlation between dosage of fentanyl given and either age or percentage of total body surface area burned was observed. Transient respiratory depression was observed in 17 patients (31%). No patient required intubation or additional supplemental oxygen after the conclusion of the procedure. High doses of fentanyl are required to achieve adequate analgesia during some burn wound procedures. Respiratory depression associated with fentanyl use is transient but requires adequate preparation and trained personnel. Fentanyl may be effectively integrated into the pain control strategy for patients with burn injuries.


Valuation of knowledge and ignorance in mesolimbic reward circuitry.
The pursuit of knowledge is a basic feature of human nature. However, in domains ranging from health to finance people sometimes choose to remain ignorant. Here, we show that valence is central to the process by which the human brain evaluates the opportunity to gain information, explaining why knowledge may not always be preferred. We reveal that the mesolimbic reward circuitry selectively treats the opportunity to gain knowledge about future favorable outcomes, but not unfavorable outcomes, as if it has positive utility. This neural coding predicts participants' tendency to choose knowledge about future desirable outcomes more often than undesirable ones, and to choose ignorance about future undesirable outcomes more often than desirable ones. Strikingly, participants are willing to pay both for knowledge and ignorance as a function of the expected valence of knowledge. The orbitofrontal cortex (OFC), however, responds to the opportunity to receive knowledge over ignorance regardless of the valence of the information. Connectivity between the OFC and mesolimbic circuitry could contribute to a general preference for knowledge that is also modulated by valence. Our findings characterize the importance of valence in information seeking and its underlying neural computation. This mechanism could lead to suboptimal behavior, such as when people reject medical screenings or monitor investments more during bull than bear markets.


Self-assessed bowel toxicity after external beam radiotherapy for prostate cancer--predictive factors on irritative symptoms, incontinence and rectal bleeding.
The aim of the study was to evaluate self-assessed bowel toxicity after radiotherapy (RT) for prostate cancer. In contrast to rectal bleeding, information concerning irritative symptoms (rectal urgency, pain) and incontinence after RT has not been adequately documented and reported in the past. Patients (n = 286) have been surveyed prospectively before (A), at the last day (70.2-72.0 Gy; B), a median time of two (C) and 16 months after RT (D) using a validated questionnaire (Expanded Prostate Cancer Index Composite). Bowel domain score changes were analyzed and patient-/dose-volume-related factors tested for a predictive value on three separate factors (subscales): irritative symptoms, incontinence and rectal bleeding. Irritative symptoms were most strongly affected in the acute phase, but the scores of all subscales remained slightly lower at time D in comparison to baseline scores. Good correlations (correlation indices >0.4; p < 0.001 for all) were found between irritative and incontinence function/bother scores at times B-D, suggesting the presence of an urge incontinence for the majority of patients who reported uncontrolled leakage of stool. Planning target volume (PTV), haemorrhoids and stroke in past history were found to be independent predictive factors for rectal bleeding at time D. Chronic renal failure predisposed for lower irritative scores at time D. Paradoxically, patients with greater rectum volumes inside higher isodose levels presented with higher quality of life scores in the irritative and incontinence subscales. PTV and specific comorbidities are important predictive factors on adverse bowel quality of life changes after RT for prostate cancer. However, greater rectum volumes inside high isodose levels have not been found to be associated with lower quality of life scores.


Vitamin D and calcium in the prevention of prostate and colon cancer: new approaches for the identification of needs.
Identification of the mechanisms involved in the pathology of nutrient deficiency provides an understanding of nutrient functions, their role in metabolism, and interactions between nutrients. However, evidence has emerged in recent years that low (suboptimal) intakes of micronutrients are associated with an elevated risk of chronic diseases. The description of micronutrient associations with chronic disease as a deficiency disease does not capture the complexity of these relations. It implies a significant oversimplification of this relation and detracts from the need for development of new approaches to this area of study. Epidemiologic study designs are essential for progress in understanding the micronutrient-chronic-disease relations, and these are described. Two areas wherein epidemiological tools could be incorporated into experimental designs have been vitamin D and prostate cancer, and vitamin D and colon cancer. In each case, biomarkers of exposure, intermediary markers, and mechanisms have been identified and could be implemented in new experimental designs. Measures of exposure would be improved by incorporation of measurements of vitamin D status such as serum 25-hydroxyvitamin D measurements. Several intermediary markers are discussed and may be useful in the characterization of responses. Such developments should aid in the interpretation of studies and identify vitamin D, as well as calcium intakes, that will aid in the prevention of prostate and colon cancer.


Higher-order chromatin domains link eQTLs with the expression of far-away genes.
Distal expression quantitative trait loci (distal eQTLs) are genetic mutations that affect the expression of genes genomically far away. However, the mechanisms that cause a distal eQTL to modulate gene expression are not yet clear. Recent high-resolution chromosome conformation capture experiments along with a growing database of eQTLs provide an opportunity to understand the spatial mechanisms influencing distal eQTL associations on a genome-wide scale. We test the hypothesis that spatial proximity contributes to eQTL-gene regulation in the context of the higher-order domain structure of chromatin as determined from recent Hi-C chromosome conformation experiments. This analysis suggests that the large-scale topology of chromatin is coupled with eQTL associations by providing evidence that eQTLs are in general spatially close to their target genes, occur often around topological domain boundaries and preferentially associate with genes across domains. We also find that within-domain eQTLs that overlap with regulatory elements such as promoters and enhancers are spatially more close than the overall set of within-domain eQTLs, suggesting that spatial proximity derived from the domain structure in chromatin plays an important role in the regulation of gene expression.


Polymorphic variability in the interleukin (IL)-1beta promoter conditions susceptibility to severe malarial anemia and functional changes in IL-1beta production.
Interleukin (IL)-1beta is a cytokine released as part of the innate immune response to Plasmodium falciparum. Because the role played by IL-1beta polymorphic variability in conditioning the immunopathogenesis of severe malarial anemia (SMA) remains undefined, relationships between IL-1beta promoter variants (-31C/T and -511A/G), SMA (hemoglobin [Hb] level <6.0 g/dL), and circulating IL-1beta levels were investigated in children with parasitemia (n= 566) from western Kenya. The IL-1beta promoter haplotype -31C/-511A (CA) was associated with increased risk of SMA (Hb level <6.0 g/dL; odds ratio [OR], 1.98 [95% confidence interval {CI}, 1.55-2.27]; P < .05) and reduced circulating IL-1beta levels (p <.05). The TA (-31T/-511A) haplotype was nonsignificantly associated with protection against SMA (OR, 0.52 [95% CI, 0.18-1.16]; p =.11) and elevated IL-1beta production ( p<.05). Compared with the non-SMA group, children with SMA had significantly lower IL-1beta levels and nonsignificant elevations in both IL-1 receptor antagonist (IL-1Ra) and the ratio of IL-1Ra to IL-1beta. The results presented demonstrate that variation in IL-1beta promoter conditions susceptibility to SMA and functional changes in circulating IL-1beta levels.


Effects of microwaves on membranes of hematopoietic cells in their structural and functional organization.
The role of cell membranes in stimulating and inhibiting the effects of microwaves was investigated in experiments carried out with a suspension of murine bone marrow cells irradiated with microwaves in vitro [f = 2.45 GHz, CW, specific absorption rate (SAR) = 12 W/kg]. Results obtained by means of a structural probe, 2.4-TNS, indicate that no structural changes occur in the region of the protein-lipid interphase under conditions of short-term irradiation with microwaves that induced temperatures in the range 36-45 degrees C (exposure time 315 and 525 s, respectively). Investigation of one functional parameter--the ability to produce hematopoietic colonies in the spleen after transplantation of the bone marrow irradiated in vitro by microwaves--indicated the possibility of affecting stimulatory and inhibitory effects of microwaves by using a blocker of cell receptors, Trimepranol. The role of microwaves as a physical factor interfering in the process of cell proliferation at the level of receptor regulation is discussed.


The mediating role of anger in the relationship between PTSD symptoms and impulsivity.
Research indicates a significant relationship between posttraumatic stress disorder (PTSD) and anger (Olatunji, Ciesielski, & Tolin, 2010; Orth & Wieland, 2006). Individuals may seek urgent coping to deal with the distress of anger, which is a mobilizing and action-oriented emotion (Novaco & Chemtob, 2002); possibly in the form of impulsive actions consistent with impulsivity's association with anger (Milligan & Waller, 2001; Whiteside & Lynam, 2001). This could be 1 of the explanations for the relationship between PTSD and impulsivity (Kotler, Julian, Efront, & Amir, 2001; Ledgerwood & Petry, 2006). The present study assessed the mediating role of anger between PTSD (overall scores and subscales of arousal and negative alterations in mood/cognitions) and impulsivity, using gender as a covariate of impulsivity. The PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), Dimensions of Anger Reaction scale-5, and the UPPS Impulsivity Scale were administered to a sample of 244 undergraduate students with a trauma history. Results based on 1000 bootstrapped samples indicated significant direct effects of PTSD (overall and 2 subscales) on anger, of anger on impulsivity, and of PTSD (overall and 2 subscales) on impulsivity. Further, anger significantly mediated the relationship between PTSD (overall and 2 subscales) and impulsivity, consistent with the hypothesized models. Results suggest that impulsivity aims at coping with distressing anger, possibly explaining the presence of substance usage, and other impulsive behaviors in people with PTSD. Further, anger probably serves as a mobilizing and action-oriented emotion coupled with PTSD symptoms.


A Rise in ROS and EPS Production: New Insights into the Trichodesmium erythraeum Response to Ocean Acidification.
The diazotrophic cyanobacterium Trichodesmium is thought to be a major contributor to the new N in parts of the oligotrophic, subtropical, and tropical oceans. In this study, physiological and biochemical methods and transcriptome sequencing were used to investigate the influences of ocean acidification (OA) on Trichodesmium erythraeum (T. erythraeum). We presented evidence that OA caused by CO2 slowed the growth rate and physiological activity of T. erythraeum. OA led to reduced development of proportion of the vegetative cells into diazocytes which included up-regulated genes of nitrogen fixation. Reactive oxygen species (ROS) accumulation was increased due to the disruption of photosynthetic electron transport and decrease in antioxidant enzyme activities under acidified conditions. This study showed that OA increased the amounts of (exopolysaccharides) EPS in T. erythraeum, and the key genes of ribose-5-phosphate (R5P) and glycosyltransferases (Tery_3818) were up-regulated. These results provide new insight into how ROS and EPS of T. erythraeum increase in an acidified future ocean to cope with OA-imposed stress.


Bone tissue quality in patients with monoclonal gammopathy of uncertain significance.
Monoclonal gammopathy of uncertain significance (MGUS) is highly prevalent in older adults and affects bone structure, with osteoporosis and increased risk of fractures in up to 14% of affected patients. Dual-energy X-ray absorptiometry (DXA), the standard technique for diagnosing osteoporosis, is ineffective to reveal microstructure and bone quality in this disease. We conducted a cross-sectional study of patients with MGUS, recruited consecutively from the Hematology and Internal Medicine Departments of Hospital del Mar, Barcelona, between January 2011 and January 2018. Medical records, clinical results and spinal X-ray images were collected. Bone mineral density (BMD) at hip and spine was measured by DXA and Bone Material Strength index (BMSi) by impact microindentation on the tibial mid-shaft. Thirty-nine patients with MGUS and 65 age-matched controls without previous fractures were included. In the MGUS group, 11 (28.2%) patients had prevalent fractures, nearly half of them vertebral (n = 5, 45.45%). Compared to controls, MGUS patients had significantly lower BMSi, a mean (SD) of 70.72 (9.70) vs. 78.29 (8.70), p = 0.001, and lower spinal BMD values (0.900 [0.159] vs. 1.003 [0.168], respectively, p = 0.012), but no significant differences at femoral neck and total hip. No association was observed between BMSi and DXA. Bone remodeling markers (procollagen type-1 N propeptide, bone-alkaline phosphatase and C-terminal telopeptide of type I collagen) did not differ between the two groups. Spinal BMD and mechanical properties of bone tissue, as measured by impact microindentation, were impaired in patients with MGUS. These changes in bone tissue mechanical resistance were independent of DXA levels.


Mindfulness-based stress reduction as a stress management intervention for healthy individuals: a systematic review.
Stress is a global public health problem with several negative health consequences, including anxiety, depression, cardiovascular disease, and suicide. Mindfulness-based stress reduction offers an effective way of reducing stress by combining mindfulness meditation and yoga in an 8-week training program. The purpose of this study was to look at studies from January 2009 to January 2014 and examine whether mindfulness-based stress reduction is a potentially viable method for managing stress. A systematic search from Medline, CINAHL, and Alt HealthWatch databases was conducted for all types of quantitative articles involving mindfulness-based stress reduction. A total of 17 articles met the inclusion criteria. Of the 17 studies, 16 demonstrated positive changes in psychological or physiological outcomes related to anxiety and/or stress. Despite the limitations of not all studies using randomized controlled design, having smaller sample sizes, and having different outcomes, mindfulness-based stress reduction appears to be a promising modality for stress management.


Analysis of gene expression in Treponema denticola with differential display polymerase chain reaction.
Treponema denticola is an oral spirochete associated with the periodontal diseases. A great deal of the molecular components of T. denticola will be learned soon since its genome sequence project is on the way. One of the most important works after genome sequence is to analyze the function of these genes and their regulation. However, like many other oral pathogens, there are currently a very limited number of molecular and genetic tools available to study gene expression in T. denticola. In this article, we describe a method of adapting differential display polymerase chain reaction (ddPCR) for use in the T. denticola system. To test for effectiveness of this protocol, we used three different temperature conditions, 4 degrees C, 25 degrees C and 42 degrees C, to test for differential gene expression. With various ddPCR conditions, we found a number of genes that were expressed differentially. Some of these differentially expressed genes were cloned and sequenced and found to be homologous with the known temperature-regulated genes, including HtrA. The study indicates that the ddPCR method can be effectively used in T. denticola for analyzing gene expression under various conditions.


Biomolecular recognition on nanowire surfaces modified by the self-assembled monolayer.
Molecular recognition is one of the key factors in designing biosensors due to which nanowires functionalized with molecular recognition have attracted a lot of attention as promising candidates for nanostructures embedded in biosensors. However, the difficulty in real-world applications with analytical specificity is that molecular recognition on nanowires mainly depends on antibody modification with multistep modification procedures. Furthermore, the antibody modification suffers from nonspecific adsorption of undesired proteins in body fluid on the nanowires, which causes false responses and lowers sensitivity. Herein, we propose biomolecular recognition using surface-modified nanowires via thiolated 2-methacryloxyethyl phosphorylcholine (MPC-SH). MPC-SH enables self-assembled monolayer (SAM) modification, which contributes to the reduction of nonspecific adsorption of biomolecules onto the nanowires, and the specific capture of a target protein is attained in the presence of calcium ions. Our concept demonstrates the recognition of the biomarker protein on nanowire surfaces modified by MPC-SH SAM with a single step modification procedure.


School-aged children's experiences of postoperative music medicine on pain, distress, and anxiety.
To test whether postoperative music listening reduces morphine consumption and influence pain, distress, and anxiety after day surgery and to describe the experience of postoperative music listening in school-aged children who had undergone day surgery. Music medicine has been proposed to reduce distress, anxiety, and pain. There has been no other study that evaluates effects of music medicine (MusiCure) in children after minor surgery. Numbers of participants who required analgesics, individual doses, objective pain scores (Face, Legs, Activity, Cry, Consolability [FLACC]), vital signs, and administration of anti-emetics were documented during postoperative recovery stay. Self-reported pain (Coloured Analogue Scale [CAS]), distress (Facial Affective Scale [FAS]), and anxiety (short State-Trait Anxiety Inventory [STAI]) were recorded before and after surgery. In conjunction with the completed intervention semi-structured qualitative interviews were conducted. Data were recorded from 80 children aged 7-16. Forty participants were randomized to music medicine and another 40 participants to a control group. We found evidence that children in the music group received less morphine in the postoperative care unit, 1/40 compared to 9/40 in the control group. Children's individual FAS scores were reduced but no other significant differences between the two groups concerning FAS, CAS, FLACC, short STAI, and vital signs were shown. Children experienced the music as 'calming and relaxing.' Music medicine reduced the requirement of morphine and decreased the distress after minor surgery but did not else influence the postoperative care.


Therapeutic effects of propolis essential oil on anxiety of restraint-stressed mice.
Propolis has a broad spectrum of biological activities; however, whether its essential oils have neuroprotective effects is unknown. In this study, we found that propolis essential oil (PEO) could significantly reverse the anxiety-like behavior of restraint-stressed mice, and has no effect on locomotor activity. Furthermore, PEO significantly decreased the plasma levels of cortisol (CORT), adrenocorticotropic hormone (ACTH) and malondialdehyde (MDA), whereas it increased the activity of superoxide dismutase (SOD) in restraint-stressed mice. These results strongly suggest that PEO has therapeutic effects on anxiety through antagonizing the hyperfunction of hypothalamic-pituitary-adrenal (HPA) axis and improving the ability of antioxidation in brain tissue.


Alendronate and estrogen effects in postmenopausal women with low bone mineral density. Alendronate/Estrogen Study Group.
The bisphosphonate alendronate and conjugated equine estrogens are both widely used for the treatment of postmenopausal osteoporosis. Acting by different mechanisms, these two agents decrease bone resorption and thereby increase or preserve bone mineral density (BMD). The comparative and combined effects of these medications have not been rigorously studied. This prospective, double blind, placebo-controlled, randomized clinical trial examined the effects of oral alendronate and conjugated estrogen, in combination and separately, on BMD, biochemical markers of bone turnover, safety, and tolerability in 425 hysterectomized postmenopausal women with low bone mass. In addition, bone biopsy with histomorphometry was performed in a subset of subjects. Treatment included placebo, alendronate (10 mg daily), conjugated equine estrogen (CEE; 0.625 mg daily), or alendronate (10 mg daily) plus CEE (0.625 mg daily) for 2 yr. All of the women received a supplement of 500 mg calcium daily. At 2 yr, placebo-treated patients showed a mean 0.6% loss in lumbar spine BMD, compared with mean increases in women receiving alendronate, CEE, and alendronate plus CEE of 6.0% (P < 0.001 vs. placebo), 6.0% (P < 0.001 vs. placebo), and 8.3% (P < 0.001 vs. placebo and CEE; P = 0.022 vs. alendronate), respectively. The corresponding changes in total proximal femur bone mineral density were +4.0%, +3.4%, +4.7%, and +0.3% for the alendronate, estrogen, alendronate plus estrogen, and placebo groups, respectively. Both alendronate and CEE significantly decreased biochemical markers of bone turnover, specifically urinary N-telopeptide of type I collagen and serum bone-specific alkaline phosphatase. The alendronate plus CEE combination produced slightly greater decreases in these markers than either treatment alone, but the mean absolute values remained within the normal premenopausal range. Alendronate, alone or in combination with CEE, was well tolerated. In the subset of patients who underwent bone biopsies, histomorphometry showed normal bone histology with the expected decrease in bone turnover, which was somewhat more pronounced in the combination group. Thus, alendronate and estrogen produced favorable effects on BMD. Combined use of alendronate and estrogen produced somewhat larger increases in BMD than either agent alone and was well tolerated.


Effects of red wine on endothelial function: postprandial studies vs clinical trials.
There are several epidemiological studies suggesting that moderate daily consumption of red wine may reduce cardiovascular risk. Additionally, results from a great number of in vitro studies indicate that constituents found in red wine are responsible for quite a few beneficial effects on endothelial cells. However, comparison of postprandial studies and clinical trials concerning red wine consumption leads to controversial results about its effect on endothelial function and especially flow-mediated dilatation (FMD). Endothelial function is an early indicator of atherosclerosis and vessel damage and at the same time, it is an independent prognostic factor for cardiovascular risk. Therefore, it is very important to investigate the known acute postprandial effects of red wine consumption, which is highly advised by dieticians and doctors, especially in high-risk populations, such as patients with coronary artery disease (CAD). This is a review of studies investigating acute and short-term effects of red wine on endothelial function, as well as relevant in vitro studies. Analysis of all data about the acute effects of red wine constituents on endothelial function, is inconclusive and it is obvious that new studies are necessary in order to elucidate this matter. Undoubtedly, one should be very careful in suggesting red wine consumption in high-risk populations, as its acute postprandial effect is not yet clear.