Gremlin2 Activates Fibroblasts to Promote Pulmonary Fibrosis Through the Bone Morphogenic Protein Pathway.
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease causing unremitting extracellular matrix deposition. Transforming growth factor-β (TGF-β) superfamily involves bone morphogenetic proteins (BMPs) and TGF-β, and the balance between the activation of TGF-β-dependent SMADs (Smad2/3) and BMP-dependent SMADs (Smad1/5/8) is essential for fibrosis process. GREM2, initially identified as a TGF-β-inducible gene, encodes a small secreted glycoprotein belonging to a group of matricellular proteins, its role in lung fibrosis is not clear. Here, we identified Gremlin2 as a key regulator of fibroblast activation. Gremlin2 was highly expressed in the serum and lung tissues in IPF patients. Bleomycin-induced lung fibrosis model exhibited high expression of Gremlin2 in the bronchoalveolar lavage fluid (BALF) and lung tissue. Isolation of primary cells from bleomycin-induced fibrosis lung showed a good correlation of Gremlin2 and Acta2 (α-SMA) expressions. Overexpression of Gremlin2 in human fetal lung fibroblast 1 (HFL-1) cells increased its invasion and migration. Furthermore, Gremlin2 regulates fibrosis functions through mediating TGF-β/BMP signaling, in which Gremlin2 may activate TGF-β signaling and inhibit BMP signaling. Therefore, we provided in vivo and in vitro evidence to demonstrate that Gremlin2 may be a potential therapeutic target for the treatment of IPF.


IMMUNE MECHANISMS IN PARABIOSIS INTOXICATION.
When A strain mice are placed in parabiotic union with (A x C57Bl/1)F(1) hybrid partners, the parental strain partners are polycythemic and the hybrids anemic from the 5th through the 16th parabiosis days. All hybrids develop clinical intoxication between the 7th and the 12th days, and no pairs survive to 1 month. Long-term survival of parabiotic pairs can be achieved if lethally irradiated or specifically tolerant parental strain mice are united to hybrid partners. Production of tolerance by either of these methods results in elimination of anemia-polycythemia by the 12th parabiosis day and prevents intoxication in the hybrid partners. Preimmunization of the parental strain partners against the C57Bl/1 component of the hybrid leads to a considerable intensification of day 5 anemia-polycythemia. Intoxication develops in the hybrid partners between the 4th and the 6th days after union. It is concluded that anemia is primarily responsible for the syndrome of clinical intoxication. Early anemia-polycythemia on day 5 does not depend upon an immunological mechanism, but the late anemia-polycythemia appearing between days 12 and 16 is a function of the ability of the parental strain mouse to react immunologically against its hybrid partner. When neonatally thymectomized A strain mice are joined to hybrid partners, anemia-polycythemia is sustained through the 16th day and the hybrid partners develop clinical intoxication. On the other hand, when both partners are neonatally thymectomized, late anemia-polycythemia is considerably reduced, and the hybrid partners apparently do not develop clinical intoxication. It is concluded that normal hybrid mice are capable of reconstituting the immunological capacity of their thymectomized partners, whereas thymectomized hybrid mice do not have this restorative capacity. These findings are discussed in terms of their possible application to the problem of the induction of immunological tolerance in adult mice by the parabiosis procedure.


Pre- and postnatal diagnosis and outcome of fetuses and neonates with esophageal atresia and tracheoesophageal fistula.
Clinical symptoms and ultrasound signs during pregnancy could suggest the presence of esophageal atresia (EA). However, most often EA is diagnosed postnatally. The aim of our study is to evaluate the course and outcome for prenatally and postnatally diagnosed EA. In addition, we studied the outcome of isolated versus nonisolated EA. In a retrospective data analysis, ultrasound characteristics, maternal and neonatal variables as well as clinical outcome were compared for fetuses/neonates with prenatal (n = 30) or postnatal (n = 49) diagnosis of EA. Clinical outcome in terms of morbidity and mortality of isolated EA was compared with that of EA complicated by chromosomal or structural anomalies. Prenatally diagnosed children were born 2 weeks earlier than postnatally diagnosed children (36.4 weeks vs 38.2 weeks; P = 0.02). The former had higher mortality rates (30 vs 12%; P = 0.05) and more associated anomalies (80 vs 59%; P = 0.04). In both subsets, there was a high morbidity rate in the survivors (not significant). Nonisolated EA was associated with greater occurrence of polyhydramnios (53 vs 27%; P = 0.04) and higher mortality rate (28 vs 0%; P = 0.002). Mortality was significantly higher in prenatally diagnosed infants and in infants with additional congenital anomalies. Isolated EA is associated with good outcome.


Psychological foundations of human status allocation.
Competing theories of status allocation posit divergent conceptual foundations upon which human status hierarchies are built. We argue that the three prominent theories of status allocation-competence-based models, conflict-based models, and dual-pathway models-can be distinguished by the importance that they place on four key affordance dimensions: benefit-generation ability, benefit-generation willingness, cost-infliction ability, and cost-infliction willingness. In the current study, we test competing theoretical predictions about the relative centrality of each affordance dimension to clarify the foundations of human status allocation. We examined the extent to which American raters' (n = 515) perceptions of the benefit-generation and cost-infliction affordances of 240 personal characteristics predict the status impacts of those same personal characteristics as determined by separate groups of raters (n = 2,751) across 14 nations. Benefit-generation and cost-infliction affordances were both positively associated with status allocation at the zero-order level. However, the unique effects of benefit-generation affordances explained most of the variance in status allocation when competing with cost-infliction affordances, whereas cost-infliction affordances were weak or null predictors. This finding suggests that inflicting costs without generating benefits does not reliably increase status in the minds of others among established human groups around the world. Overall, the findings bolster competence-based theories of status allocation but offer little support for conflict-based and dual-pathway models.


Highly fluorescent and photostable probe for long-term bacterial viability assay based on aggregation-induced emission.
Long-term tracking of bacterial viability is of great importance for monitoring the viability change of bacteria under storage, evaluating disinfection efficiency, as well as for studying the pharmacokinetic and pharmacodynamic properties of antibacterials. Most of the conventional viability dyes, however, suffer from high toxicity and/or poor photostability, making them unsuitable for long-term studies. In this work, an aggregation-induced emission molecule, TPE-2BA, which can differentiate dead and living bacteria and serve as a highly fluorescent and photostable probe for long-term viability assay. TPE-2BA is a cell-impermeable DNA stain that binds to the groove of double-stranded DNA. Bacteria with compromised membrane open the access for TPE-2BA to reach DNA, endowing it with strong emission. The feasibility of using TPE-2BA for screening effective bactericides is also demonstrated. Plate count experiment reveals that TPE-2BA poses negligible toxicity to bacteria, indicating that it is an excellent probe for long-term bacterial viability assay.


Circuit cavity electromechanics in the strong-coupling regime.
Demonstrating and exploiting the quantum nature of macroscopic mechanical objects would help us to investigate directly the limitations of quantum-based measurements and quantum information protocols, as well as to test long-standing questions about macroscopic quantum coherence. Central to this effort is the necessity of long-lived mechanical states. Previous efforts have witnessed quantum behaviour, but for a low-quality-factor mechanical system. The field of cavity optomechanics and electromechanics, in which a high-quality-factor mechanical oscillator is parametrically coupled to an electromagnetic cavity resonance, provides a practical architecture for cooling, manipulation and detection of motion at the quantum level. One requirement is strong coupling, in which the interaction between the two systems is faster than the dissipation of energy from either system. Here, by incorporating a free-standing, flexible aluminium membrane into a lumped-element superconducting resonant cavity, we have increased the single-photon coupling strength between these two systems by more than two orders of magnitude, compared to previously obtained coupling strengths. A parametric drive tone at the difference frequency between the mechanical oscillator and the cavity resonance dramatically increases the overall coupling strength, allowing us to completely enter the quantum-enabled, strong-coupling regime. This is evidenced by a maximum normal-mode splitting of nearly six bare cavity linewidths. Spectroscopic measurements of these 'dressed states' are in excellent quantitative agreement with recent theoretical predictions. The basic circuit architecture presented here provides a feasible path to ground-state cooling and subsequent coherent control and measurement of long-lived quantum states of mechanical motion.


[Comparative study of platelets from healthy human donors using light microscopy and flow cytometr "Cobas micros"].
Peripheral blood platelets of 25 normal subjects were examined by optic microscopy and flow cytometry. Blood was collected routinely into tubes for Cobas Micros flow scintillator with EDTA anticoagulant. Smears were made as a monolayer and stained by May-Grünwald's method in our modification. Morphologically, 5 classes of platelets were distinguished under optic microscope: young, mature, old, macroplatelets, and irritated forms. The percentage of each class was estimated (i.e., normal platelet formula was determined). Comparison of platelet parameters obtained on a flow cytometer and optic microscopy data for subjects with high percentage of large platelets showed increased mean volume of platelets (MPV) and width of platelet volume (PDW). The curve reflecting platelet distribution by volume in these donors was characterized by strong inclination to the right and a flat plateau.


Exploring the views of academic staff on HIV/AIDS integration into the curricula: a case study of the University of Fort Hare.
As a clarion call by Higher Education HIV/AIDS programme (HEAIDS) to South African universities, entrenching, integration and infusing the teaching and learning of HIV/AIDS in the curriculum of universities prove to be a sustainable solution to changing risky behaviour and attitudes of university students towards HIV/AIDS. The majority of students in South African universities lack general awareness and education in HIV/AIDS. This raises the need to produce graduates who are knowledgeable and have a positive attitude regarding HIV/AIDS. A pilot study on HIV/AIDS curriculum integration at the University of Fort Hare involved academic staff was done. A qualitative case study approach was used to describe the process and effectiveness of the curriculum integration process. The data collection was through evaluation forms, reports and a focus group interview. Data were analysed using content analysis. Guskey's model for professional development was followed to understand the process and effect of curriculum integration. Initially, the academic staff anticipated that the HIV/AIDS curriculum integration process would result in credit overload for students, time constraints and increased workload. Later, most academic staff affirmed the benefits of being involved in the project such as improving teaching and facilitation styles and research.


The effect of capsule tension ring on posterior capsule opacification: A meta-analysis.
Posterior capsule opacification is one of the most common complications after cataract surgery. Studies have suggested that the introduction of a capsule tension ring might play a critical role in the prevention of capsule opacification, yet quantitative evidence is still lacking. This work consists of a meta-analysis on available data in order to explore the influence of a capsule tension ring on posterior capsule opacification. A comprehensive review of the literature on capsule tension ring and posterior capsule opacification was carried out using the Embase, Pubmed, Web of Science, and Cochrane electronic databases. The selected studies included randomized controlled trials, retrospective studies and prospective studies published before June 2020. The studies of interest were selected by two reviewers independently from the included studies. Odds ratios (ORs) and standardized mean differences (SMD) were used in order to assess the association. A fixed-effects model or a random-effects model was applied to combine data according to heterogeneities. Sensitivity analysis was used to assess the heterogeneity of the studies. Publication bias was estimated using the Egger test. Statistical analysis was performed using the stata15.1 software. The meta-analysis included in total 8 studies involving 379 cases and 333 controls. There was a statistically significant difference of Nd:YAG laser capsulotomy rate (OR=0.241, 95% CI: 0.145, 0.400 I2=42.1%) between the capsule tension ring group and the control group, indicating that the tension ring reduced the Nd:YAG laser capsulotomy rate. Further studies with continuous data also revealed that the use of capsule tension ring was associated with a lower posterior capsule opacification score (SMD = -1.402, 95% CI: -2.448, -0.355 I2=95.0%). The sensitivity analysis suggested that the result of the re-combined analysis did not change notably, indicating that the result was reliable and stable. Both pooled analysis showed no evidence of publication bias. The findings of this meta-analysis confirmed that capsule tension ring might reduce capsule opacification. Further studies should be made to validate the result.


Does nutritional intake differ between children with autism spectrum disorders and children with typical development?
Consumption of macro- and micronutrients and food group servings by children with autism spectrum disorders (ASDs; n = 46) and typical development (n = 31) were compared using 3-day diet records. Children with ASDs consumed significantly more vitamin B6 and E and non-dairy protein servings, less calcium, and fewer dairy servings (p < .05). The significantly lower dairy serving intake persisted after controlling for child age and sex and parental dietary restrictions, and excluding children on the gluten-free casein-free (GFCF) diet. Large proportions of children in both groups did not meet national recommendations for daily intake of fiber, calcium, iron, vitamin E, and vitamin D.


Cross-country differences in basal and stress-induced cortisol secretion in older adults.
Several studies have emphasized the association between socioeconomic status (SES) and inadequate response of the biological stress system. However, other factors related to SES are rarely considered, such as cultural values, social norms, organization, language and communication skills, which raises the need to investigate cross-country differences in stress response. Although some studies have shown differences in cortisol levels between immigrants and natives, there is no cross-country evidence regarding cortisol levels in country-native elders. This is particularly important given the high prevalence of stress-related disorders across nations during aging. The current study examined basal diurnal and reactive cortisol levels in healthy older adults living in two different countries. Salivary cortisol of 260 older adults from Canada and Brazil were analyzed. Diurnal cortisol was measured in saliva samples collected at home throughout two working days at awakening, 30 min after waking, 1400 h, 1600 h and before bedtime. Cortisol reactivity was assessed in response to the Trier Social Stress Test (TSST) in both populations. Our results showed that even under similar health status, psychological and cognitive characteristics, Brazilian elders exhibited higher basal and stress-induced cortisol secretion compared to the Canadian participants. These findings suggest that country context may modulate cortisol secretion and could impact the population health.


Bonding the gap between petralit and ceromers: with case reviews.
The search for a metal-free, aesthetic restoration with optimal strength, longevity, and comfort easily dates back to the 19th century. However, the popularity of adhesively retained restorations has reached an all-time high due to improvements in wear, post-op sensitivity, bond material and strength, and aesthetic quality. Targis/Vectris, a ceromer restorative material introduced in 1997 by Ivoclar-Williams, is a ceramic optimized polymer that produces a strong fiber-reinforced tooth-colored restoration. It allows the clinician to fabricate metal-free restorations without the fracture potential seen with ceramic materials. Long-term longitudinal studies of this restorative material will be the litmus test, but we now have 10-year studies that show very promising results.


Conformal invariants for multiply connected surfaces: Application to landmark curve-based brain morphometry analysis.
Landmark curves were widely adopted in neuroimaging research for surface correspondence computation and quantified morphometry analysis. However, most of the landmark based morphometry studies only focused on landmark curve shape difference. Here we propose to compute a set of conformal invariant-based shape indices, which are associated with the landmark curve induced boundary lengths in the hyperbolic parameter domain. Such shape indices may be used to identify which surfaces are conformally equivalent and further quantitatively measure surface deformation. With the surface Ricci flow method, we can conformally map a multiply connected surface to the Poincaré disk. Our algorithm provides a stable method to compute the shape index values in the 2D (Poincaré Disk) parameter domain. The proposed shape indices are succinct, intrinsic and informative. Experimental results with synthetic data and 3D MRI data demonstrate that our method is invariant under isometric transformations and able to detect brain surface abnormalities. We also applied the new shape indices to analyze brain morphometry abnormalities associated with Alzheimer' s disease (AD). We studied the baseline MRI scans of a set of healthy control and AD patients from the Alzheimer' s Disease Neuroimaging Initiative (ADNI: 30 healthy control subjects vs. 30 AD patients). Although the lengths of the landmarks in Euclidean space, cortical surface area, and volume features did not differ between the two groups, our conformal invariant based shape indices revealed significant differences by Hotelling' s T2 test. The novel conformal invariant shape indices may offer a new sensitive biomarker and enrich our brain imaging analysis toolset for studying diagnosis and prognosis of AD.


Histological progression of non-alcoholic fatty liver disease: a critical reassessment based on liver sampling variability.
In non-alcoholic fatty liver disease, histological lesions display a significant sampling variability that is ignored when interpreting histological progression during natural history or therapeutic interventions. To provide a method taking into account sampling variability when interpreting crude histological data, and to investigate how this alters the conclusions of available studies. Natural history studies detailing histological progression and therapeutic trials were compared with the results of a previously published sampling variability study. Natural history studies showed an improvement in steatosis, which was significantly higher than expected from sampling variability (47% vs. 8%, P < 0.0001). In contrast, no study showed a change in activity grade or ballooning higher than that of sampling variability. There was only a marginal effect on fibrosis with no convincing demonstration of a worsening of fibrosis, a conclusion contrary to what individual studies have claimed. Some insulin sensitizing drugs and anti-obesity surgery significantly improved steatosis, while most did not significantly impact on fibrosis or activity. Sampling variability of liver biopsy is an overlooked confounding factor that should be considered systematically when interpreting histological progression in patients with non-alcoholic fatty liver disease.


A potential growth thermal index for estimating juvenile Atlantic salmon (Salmo salar) size-at-age across geographical scales.
We present a potential growth thermal index (PGTI) and assess its correlation with juvenile Atlantic salmon Salmo salar fork length data collected near the end of the growth season in a range of latitudinal locations and geographic scales (watershed, regional, continental) across the American north-east. The PGTI is based on two components: a water temperature-dependent growth curve and a water temperature time series continuously describing the thermal environment preceding fish sampling. Testing various shapes and characteristics of the temperature-growth curve against fish length data revealed strong positive correlations for all combinations. PGTI warming, calculated only from the beginning of the growth season until maximum summer temperature is reached, consistently performed well in explaining fish size-at-age across the latitudinal gradient and the three geographic scales that were considered. Varying thermal contrasts created by repeat subsampling of the dataset showed that fish length is better explained by the level of thermal contrast within the dataset than the geographical scale of analysis. A simple generalized linear model using a log link function with PGTI warming, fish density and water discharge as predictors explained 87% of the variance of size-at-age of 0+ and 1+ juvenile Atlantic salmon.


Silicon nitride CMOS-compatible platform for integrated photonics applications at visible wavelengths.
Silicon nitride is demonstrated as a high performance and cost-effective solution for dense integrated photonic circuits in the visible spectrum. Experimental results for nanophotonic waveguides fabricated in a standard CMOS pilot line with losses below 0.71dB/cm in an aqueous environment and 0.51dB/cm with silicon dioxide cladding are reported. Design and characterization of waveguide bends, grating couplers and multimode interference couplers (MMI) at a wavelength of 660 nm are presented. The index contrast of this technology enables high integration densities with insertion losses below 0.05 dB per 90° bend for radii as small as 35 µm. By a proper design of the buried oxide layer thickness, grating couplers with efficiencies above 38% for the TE polarization have been obtained.


A novel SPE-LC-MRM strategy for serum demethylzeylasteral quantitation developed with an 18O-labeled internal standard.
Natural bioactive compounds (NBCs) are widely used in clinical treatment. For example, Tripterygium wilfordii Hook f. is commonly known in China as Lei-Gong-Teng which means thunder god vine. This herb is widely distributed in Eastern and Southern China, Korea, and Japan. The natural bioactive compounds of this herb can be extracted and made into tripterygium glycoside tablets. It is one of the most commonly used and effective traditional Chinese herbal medicines against rheumatoid arthritis (RA), nephrotic syndrome (NS), autoimmune hepatis (AIH), and so on. However, many NBCs are difficult to reliably quantify in the serum due to the effects of matrix and RSD. In addition, the targeted compound's internal standard (IS) is rarely sold due to the complex isotope internal standard synthesis pathway. In this study, a new quantitation method for 18O labeling combined with off-line SPE was formulated. We contrasted the recoveries and matrix effects of various separation methods in order to choose the best method. Furthermore, we optimized the conditions for SPE loading and washing. An isotopic internal standard was prepared by the 16O/18O exchanging reaction in order to eliminate the matrix effects. The method's accuracy and precision met the requirements for method validation. The recovery of this method was close to 60%. The relative standard deviation (RSD) of the high-concentration sample was 2%, and the limit of detection (LOD) was 1 ng/mL. This method could be used to analyze the clinical serum concentration of demethylzeylasteral. Sixty samples were collected from 10 patients with diabetes nephropathy. The quantitation results of demethylzeylasteral in patients' serum obtained using this method exhibited a correlation between therapeutic drug monitoring (TDM) and decreased urinary protein. This work may have broad implications for the study of drug metabolism in vivo and the clinical application of low-abundance and difficult-to-quantify NBCs.


Subcutaneous implants for long-acting drug therapy in laboratory animals may generate unintended drug reservoirs.
Long-acting therapy in laboratory animals offers advantages over the current practice of 2-3 daily drug injections. Yet little is known about the disintegration of biodegradable drug implants in rodents. Compare bioavailability of buprenorphine with the biodegradation of lipid-encapsulated subcutaneous drug pellets. Pharmacokinetic and histopathology studies were conducted in BALB/c female mice implanted with cholesterol-buprenorphine drug pellets. Drug levels are below the level of detection (0.5 ng/mL plasma) within 4-5 days of implant. However, necroscopy revealed that interstitial tissues begin to seal implants within a week. Visual inspection of the implant site revealed no evidence of inflammation or edema associated with the cholesterol-drug residue. Chemical analyses demonstrated that the residues contained 10-13% of the initial opiate dose for at least two weeks post implant. The results demonstrate that biodegradable scaffolds can become sequestered in the subcutaneous space. Drug implants can retain significant and unintended reservoirs of drugs.


Membrane efflux and influx modulate both multidrug resistance and virulence of Klebsiella pneumoniae in a Caenorhabditis elegans model.
Cross-resistance to cefoxitin (FOX), chloramphenicol (CMP), and quinolones (nalidixic acid [NAL]) related to a putative efflux system overexpression has recently been reported for Klebsiella pneumoniae. The potential impact of this multidrug resistance (MDR) on the virulence of K. pneumoniae was evaluated in the Caenorhabditis elegans model. For 2 of the 3 MDR clinical isolates studied, a significant increase in acrB transcription was found in comparison with their antibiotic-susceptible revertants. ATCC 138821 and MDR, revertant, and derivative strains with altered porin expression were studied. Strains proved or suspected to overexpress an efflux system were significantly more virulent than the ATCC and revertant strains (time to kill 50% of nematodes [LT(50)] in days: 3.4 to 3.8 ± 0.2 versus 4.1 to 4.4 ± 0.3, P < 0.001). Inversely, strains with altered porin expression were significantly less virulent, independently of the expression level of efflux system (LT(50) = 5.4 to 5.6 ± 0.2, P < 0.001). Altered porin expression did not change MICs of CMP and NAL but did those of FOX (4 to 16× MIC) and ertapenem (16 to 64× MIC). The strains with a normally or an overexpressed efflux system that received the β-lactamase CTX-M-15 became more widely resistant without modification of their virulence potential, suggesting that balance between resistance and virulence is dependent on the type of resistance mechanisms. In conclusion, this study shows that the expression of both efflux systems and porins is a key factor not only for antibiotic resistance but also virulence potential in K. pneumoniae.


Elasticity as a biomarker for prostate cancer: a systematic review.
To systematically review the range of methods available for assessing elasticity in the prostate and to examine its use as a biomarker for prostate cancer. A systematic review of the electronic database PubMed was performed up to December 2012. All relevant studies assessing the use of elasticity as a biomarker for prostate cancer were included except those not studying human prostates or reporting a sensitivity, specificity or quantitative elasticity value. There has been much interest in the use of elasticity in the detection of prostate cancer and there have been many publications using various methods of detection. The most common method of assessment is an imaging method, called sonoelastography. Further imaging methods include ultrasound (US), three-dimensional US and magnetic resonance elastography. These methods are reviewed for sensitivity and specificity. The other method of assessment is the mechanical method. These use quantitative elasticity values to differentiate benign from malignant areas of the prostate. This method of assessment has shown that the elasticity changes for differing Gleason grades and T stages of disease within the prostate. Quantitative elasticity values offer the potential of using 'threshold' elasticity values under which the prostate is benign. Tissue elasticity has great potential as a diagnostic and prognostic biomarker for prostate cancer and can be assessed using various methods. Currently transrectal sonoelastography has the most evidence supporting its use in clinical practice.


Preparations for Severe Winter Conditions by Emergency Health Personnel in Turkey.
Emergency and core ambulance personnel work under all environmental conditions, including severe weather condtions. We evaluated emergency medical personnel in Çanakkale, Turkey, for their degree of preparedness. A descriptive study was conducted in Çanakkale, Turkey, within 112 emergency service units and their 17 district stations. Surveys were developed to measure the level of preparedness for serious winter conditions that individual workers made for themselves, their homes, and their cars. Of the 167 survey participants, the mean age was 29.8 ± 7.9 years; 52.7% were women; more than half (54.75%) were emergency medical technicians; and 53.3% were married. Only 10.4% of those who heated their homes with natural gas had carbon monoxide detectors. Scores relating to household and individual preparation for severe winter conditions increased by participants' age (P < .003), being married (P < .000) and working in the city center (P < .021); and for men whose cars were equipped with tow ropes, extra clothing, and snow tires (P < .05). Absenteeism was higher for central-city personnel than district workers because they were less prepared for harsh winter conditions (P = .016). Many of the surveyed emergency health personel demonstrated insufficient preparations for serious winter conditions. To increase the safety and efficiency of emergency medical personnel, educational training programs should be rountinely conducted. (Disaster Med Public Health Preparedness. 2014;0:1-4).


Source apportionment of atmospheric mercury pollution in China using the GEOS-Chem model.
China is the largest atmospheric mercury (Hg) emitter in the world. Its Hg emissions and environmental impacts need to be evaluated. In this study, China's Hg emission inventory is updated to 2007 and applied in the GEOS-Chem model to simulate the Hg concentrations and depositions in China. Results indicate that simulations agree well with observed background Hg concentrations. The anthropogenic sources contributed 35-50% of THg concentration and 50-70% of total deposition in polluted regions. Sensitivity analysis was performed to assess the impacts of mercury emissions from power plants, non-ferrous metal smelters and cement plants. It is found that power plants are the most important emission sources in the North China, the Yangtze River Delta (YRD) and the Pearl River Delta (PRD) while the contribution of non-ferrous metal smelters is most significant in the Southwest China. The impacts of cement plants are significant in the YRD, PRD and Central China.


Deep cerebral microbleeds are associated with poor cholinesterase inhibitor treatment response in people with Alzheimer disease.
Cholinesterase inhibitors (ChEIs) are the most effective treatment for Alzheimer disease (AD), but the response to treatment varies. Vascular lesions are associated with the pathogenesis of AD, and cerebral microbleeds (CMBs) are an indicator of hemorrhagic vascular pathology, which can be detected through susceptibility-weighted magnetic resonance imaging (SWMRI). This study investigated the association between CMBs and ChEI treatment response in patients with AD. We reviewed the medical records of 112 Taiwanese people with mild to moderate AD and at least 2 years of ChEI treatment between 2009 and 2016. Their baseline CMBs were quantified using the Microbleed Anatomical Rating Scale on SWMRI. Cognitive function of the patients was assessed using the Mini-Mental State Examination (MMSE) and Cognitive Abilities Screening Instrument (CASI). Student t test and multivariable logistic regression were used to analyze the association between cognitive decline and CMBs. The mean age of the study population was 76.0 ± 8.0 years. In total, 79 out of 112 patients were women. The presence of deep, but not lobar CMBs at baseline was associated with a significant cognitive decline according to the MMSE and CASI, particularly in long-term memory, attention, orientation, mental manipulation, and verbal fluency. Among deep CMBs, those in the basal ganglia and thalamus were significantly associated with cognitive decline. Deep CMBs, particularly those in the basal ganglia and thalamus, but not lobar CMBs, are associated with poor response to ChEI treatment in people with AD. This can serve as a biomarker for predicting ChEI treatment response.


A drug by any other name: patients' ability to identify medication regimens and its association with adherence and health outcomes.
Understanding and organizing medication regimens can be challenging, and many patients struggle to properly dose prescribed medicine, potentially leading to less effective treatment or even harm. Generic prescriptions are increasingly common and may change in appearance, adding further complexity. The authors aimed to investigate familiarity with the drug regimen among a cohort of patients with diagnosed hypertension. Specifically, they determined the prevalence of patients' knowledge of their prescribed drug names and dosages compared to those who relied only on physical characteristics (size, shape, color) of their medications. The relationship between patients' identification strategies, self-reported adherence, and health outcomes (blood pressure control, hospitalization) were investigated. Patients who were dependent on the visual identification of their prescription medicine reported worse adherence. In addition, they had significantly lower rates of blood pressure control and greater risk of hospitalization. The ability to identify prescribed medicines by name may be helpful for screening and responding to patients at greater risk of making medication errors or being less engaged with their regimen for adherence purposes.


[Effects of Kechuanluo oral liquid on eosinophil apoptosis and its regulation factors in lung tissues of asthmatic mice].
To explore the mechanism of Kechuanluo oral liquid, a compound Chinese herbal medicine, in inhibiting allergic airway inflammation by observing the effects of Kechuanluo on eosinophil (EOS) apoptosis and its regulation factors in asthmatic mice. Fifty-six BALB/c mice were randomly divided into normal control group (n=16), untreated group (n=16), Western medicine group (n=12) and Kechuanluo group (n=12). Except for the mice in normal control group, asthma was induced in BALB/c mice by using ovalbumin (OVA) and potassium aluminium sulfate. The mice were intragastrically administered with normal saline, Kechuanluo (30 ml/kg daily) and prednisolone tablets (10 mg/kg daily) respectively for two weeks. At 0 hour, the 3rd, 7th and 14th day after the end of OVA sensitization, the EOSs of lung tissues were counted by improved-Giemsa staining method; immunohistochemical method and image analysis were used to detect the expressions of Fas, FasL and Bcl-XL in the EOSs in the four groups; and apoptotic rates of the EOSs in the lung tissues of asthmatic mice were detected by terminal deoxynucleotidyl transferase-mediated biotin-dUTP nick end labeling (TUNEL) technique. Compared with the untreated group, airway inflammations of the mice in the Kechualuo group and Western medicine group were lessened and the EOS counts decreased on the 3rd, 7th and 14th day after the last OVA sensitization (P<0.05). On the 3rd day, the EOSs apoptotic rates, the expression areas of Fas in the EOSs and FasL in the lung tissues were significantly higher in the Kechuanluo group than those in the untreated group (P<0.01), furthermore, the EOS apoptotic rate reached the peak level. Inversely, the EOS count and the expression area of Bcl-XL in the EOSs were obviously lower in the Kechuanluo group (P<0.05). On the 7th and 14th day, the expression areas of Fas and Bcl-XL in the EOSs were significantly decreased in the Kechuanluo group (P<0.01), and on the 14th day, the EOS apoptotic rate and the expression area of FasL in the lung tissues were obviously lower either. The effects exhibited in the Western medicine group were similar to those in the Kechuanluo group. There is airway inflammation with eosinophilic infiltration in asthmatic mice, accompanied with suppressed apoptosis and delayed apoptosis. Kechuanluo can induce and accelerate EOS apoptosis in early inflammation by inhibiting eosinophilic inflammation, improving Fas expression in EOSs and FasL expression in the lung tissues, and reducing Bcl-XL expression in EOSs.


Anaphylaxis and intimate behaviour.
Intimate behaviours may represent an unusual way of exposure to a culprit allergen, or the frame for sex-related allergies due to triggers typically linked to that situation. The present review aims at summarizing the state of the art about the topic, in order to spread the awareness and the basic know-how in the field of sexual-related allergies. Kiss-related IgE-mediated reactions are caused in sensitized partners mainly by the passive transport of allergenic molecules through saliva, skin or oral mucosa. It has also been recently suggested that kissing may act as an epicutaneous way for induction of allergic sensitization. Among food and drugs, not only but mostly, peanuts and beta-lactams, respectively, are the usual trigger. Although controversial, 1-hour wait before kissing and a proper mouth cleaning have been suggested as prevention strategies. Sexual intercourse related local or systemic symptoms can be caused by seminal plasma hypersensitivity, an IgE-mediated/type IV reaction due to prostate-specific antigen, which carries high homology to the canine prostatic kallikrein (Can f 5). Although applied to few patients, successful desensitization and immunotherapy protocols have been proposed. Intimate behaviours are possible modalities of contact with the allergen. The exact prevalence of such hypersensitivity reactions is not known, but for its implications on Quality of Life and reproductive wishes, the possible link between sex and allergy should become part of the personal culture of clinical allergists and every clinician, in order to extend and improve the diagnosis of unusual or unexplained conditions.


[Immunochemical analysis of lectin receptors in the structure of trophoblastic beta 1-glycoprotein and pregnancy-associated alpha 2-glycoprotein].
Trophoblastic beta-glycoprotein (TBG), pregnancy-associated alpha 2-glycoprotein (AGP) and alpha-fetoprotein (AFP) bind to concanavalin A, phytohemagglutinin P and pea lectin. Lentil lectin interacts with TBG only, whereas peanut lectin and castor bean lectin are characterized by affinity to AGP. Hence, TBG, AGP and AFP contain the following carbohydrate components: alpha-D-mannose, alpha-D-glucose, N-acetyl-D-glucosamine and N-acetyl-D-galactosamine. In addition, AGP contains beta-D-galactose.


Siblings' coping strategies and mental health services: a national study of siblings of persons with schizophrenia.
This study examined the helpfulness of coping strategies and the relative importance of mental health services in coping with schizophrenia from the perspective of siblings. This article presents selected survey data from a national study of 746 respondents that investigated the impact of schizophrenia on siblings' lives. The authors developed the Friedrich-Lively Instrument to Assess the Impact of Schizophrenia on Siblings (FLIISS), a closed-ended questionnaire that included questions about coping strategies and mental health services. Respondents identified services for the ill sibling, including symptom control, adequate housing, and long-term planning, as more important than direct services for themselves. The top-ranked coping strategies were education about schizophrenia, a supportive family, and seeing the ill sibling suffer less because symptoms were controlled. Understanding that families were not to blame for schizophrenia was the most helpful coping strategy for nearly three-fourths of siblings. Siblings had little contact with providers in the past; yet the majority of siblings wanted providers to be available to answer questions and clarify their role in future care. At the time of the study, respondents provided social support and helped with crises, but few coordinated the total care. Siblings identified multiple ways that providers can support and assist them in coping with the impact of schizophrenia. Education and support for siblings without schizophrenia and services for their ill siblings will become increasingly important for the well-being of siblings as they are faced with the responsibility of being the primary caregivers in the future.


Evaluation of a staff well-being program in a pediatric oncology, hematology, and palliative care services group.
Challenges experienced by staff in the Oncology Services Group at Queensland Children's Hospital led to issues with staff retention, well-being, and stress on team culture. Therefore, a customized program was developed through a needs analysis to improve the well-being and resilience of oncology staff, enabling them to cope with stressors and critical incidents inherent in their everyday work and to flourish. The program included education, on-site counselors, mindfulness sessions, debriefing, well-being resources, and improved engagement, support, and communication. Evaluation of the program in the first year examined program participation, staff feedback following education workshops and mindfulness sessions, staff retention rates, and the results of an annual organizational staff survey and a program outcome survey. Approximately 76% of staff attended the Introduction to Well-being workshop, and 98% of responses to survey questions were positive. Staff also provided positive feedback on the other well-being workshops and sessions embedded within existing education programs. Employee Assistance Program counseling sessions had an 81% uptake, with a wide variety of presenting issues, 62% related to work. All participants in mindfulness sessions agreed that it was a valuable tool to improve clinical practice, 94% said it had an immediate positive impact on their well-being, and 70% agreed that they were applying mindfulness principles outside the sessions. Staff retention and turnover improved. Staff reported a positive effect on awareness of self-care, addressing risks to resilience, seeking support from trusted colleagues, coping with critical incidents, and the ability to interact positively with patients and families. The evaluation showed a positive impact on staff well-being. Although there was a wide variety of successful interventions reported in the literature, sustainability needs to be considered. Feedback on this program found that staff appreciated being listened to, valued, and supported through the strategies, and the ongoing program will continue to monitor staff needs and be responsive in building their resilience and well-being.


Iron-restricted erythropoiesis as a limitation to autologous blood donation in the erythropoietin-stimulated bone marrow.
Recombinant human erythropoietin has been demonstrated to significantly increase autologous blood procurement. To determine the importance of dietary or prescribed iron absorption, we analyzed iron-restricted erythropoiesis in this setting. No differences were found when premenopausal placebo and erythropoietin treatment groups were compared for hematocrit changes, number of units donated, percentage of phlebotomies deferred, and total blood volume procured. Seven of 10 women who had not reached menopause donated more blood iron than the apparent amount of total mobilizable iron available, demonstrating that dietary or prescribed iron had to be absorbed to donate the amount of blood iron stored. Thus oral iron absorption can potentially be a limitation to erythropoiesis in the presence of erythropoiesis therapy in women who have not reached menopause. In contrast, none of 16 women who had reached menopause and only two of 21 men required oral absorption of dietary or prescribed iron for the amount of blood iron donated. We conclude that although oral iron supplementation may not be necessary in men and in women who have reached menopause, alternatives to oral ferrous salt supplementation could be tested to determine whether such alternatives would improve the response to erythropoiesis in premenopausal women.


Skeletal muscle tissue engineering: methods to form skeletal myotubes and their applications.
Skeletal muscle tissue engineering (SMTE) aims to repair or regenerate defective skeletal muscle tissue lost by traumatic injury, tumor ablation, or muscular disease. However, two decades after the introduction of SMTE, the engineering of functional skeletal muscle in the laboratory still remains a great challenge, and numerous techniques for growing functional muscle tissues are constantly being developed. This article reviews the recent findings regarding the methodology and various technical aspects of SMTE, including cell alignment and differentiation. We describe the structure and organization of muscle and discuss the methods for myoblast alignment cultured in vitro. To better understand muscle formation and to enhance the engineering of skeletal muscle, we also address the molecular basics of myogenesis and discuss different methods to induce myoblast differentiation into myotubes. We then provide an overview of different coculture systems involving skeletal muscle cells, and highlight major applications of engineered skeletal muscle tissues. Finally, potential challenges and future research directions for SMTE are outlined.


Nephrotic syndrome in autosomal dominant polycystic kidney disease.
Urinary protein excretion is generally less than 1 g/24 h in autosomal dominant polycystic kidney disease (ADPKD), and the association of the nephrotic syndrome with this condition is considered rare. A patient with ADPKD associated with nephrotic-range proteinuria is described. She exhibited a relatively rapid impairment of her renal function. An open renal biopsy revealed focal segmental glomerulosclerosis (FGS) with features consistent with secondary FGS. Twenty-one patients with ADPKD and nephrotic syndrome were retrieved from the literature. Fourteen of them (including this case) had a histopathologic evaluation, and FGS was the dominant diagnoses (five patients). Next in frequency were minimal-change disease and membranous nephropathy, with two patients each. Five other patients had a variety of diagnoses. Thus, it is difficult to ascertain if these associations are coincidental or represent a specific pathogenetic relationship. The evaluation of the data also suggests that the presence of proteinuria and nephrotic syndrome accelerates the course of ADPKD toward ESRD.


No time to wait: how many HIV-infected homosexual men are diagnosed late and consequently die? (England and Wales, 1993-2002).
To present national trends of the estimated number and proportion of late HIV diagnoses and short-term mortality following diagnosis among men who have had sex with men (MSM). To determine separately risk factors for late diagnosis and short-term mortality. Analysis of national HIV/AIDS case reports of new diagnoses linked to CD4 cell counts from the CD4 Surveillance Scheme. Inverse probability weighting adjusted for individuals with no CD4 cell count at diagnosis. Outcomes were late diagnosis (CD4 cell count <200 x 10(6) cells/l at diagnosis) and short-term mortality (death within 1 year of diagnosis). Of 14,158 new diagnoses, 31% were estimated as late diagnoses. Despite a decreasing trend (P trend <0.01) an estimated 430 (25%) MSM were still diagnosed late in 2001. Late diagnosis disproportionately affected individuals diagnosed outside London, of non-white ethnicity, and of older age. There were 710 (5.0% of 14 158) deaths within a year of HIV diagnosis. Estimated short-term mortality was 14% for MSM diagnosed late and 1% for other MSM (adjusted odds ratio, 10.8; 95% confidence interval, 7.7-15.9). Short-term mortality declined concurrently with availability of highly active antiretroviral therapy and was independently associated with age and diagnosis outside London but not ethnicity. The continued late diagnosis of one in four MSM means these individuals lose the option to start therapy early, miss opportunities to prevent further transmission and are approximately 10 times more likely to die within a year of diagnosis. Early diagnosis of all MSM in 2001 could have reduced short-term mortality by 84% and all mortality in that year by 22%.


Epoxide metabolites of arachidonate and docosahexaenoate function conversely in acute kidney injury involved in GSK3β signaling.
Acute kidney injury (AKI) causes severe morbidity and mortality for which new therapeutic strategies are needed. Docosahexaenoic acid (DHA), arachidonic acid (ARA), and their metabolites have various effects in kidney injury, but their molecular mechanisms are largely unknown. Here, we report that 14 (15)-epoxyeicosatrienoic acid [14 (15)-EET] and 19 (20)-epoxydocosapentaenoic acid [19 (20)-EDP], the major epoxide metabolites of ARA and DHA, respectively, have contradictory effects on kidney injury in a murine model of ischemia/reperfusion (I/R)-caused AKI. Specifically, 14 (15)-EET mitigated while 19 (20)-EDP exacerbated I/R kidney injury. Manipulation of the endogenous 19 (20)-EDP or 14 (15)-EET by alteration of their degradation or biosynthesis with selective inhibitors resulted in anticipated effects. These observations are supported by renal histological analysis, plasma levels of creatinine and urea nitrogen, and renal NGAL. The 14 (15)-EET significantly reversed the I/R-caused reduction in glycogen synthase kinase 3β (GSK3β) phosphorylation in murine kidney, dose-dependently inhibited the hypoxia/reoxygenation (H/R)-caused apoptosis of murine renal tubular epithelial cells (mRTECs), and reversed the H/R-caused reduction in GSK3β phosphorylation in mRTECs. In contrast, 19 (20)-EDP dose-dependently promoted H/R-caused apoptosis and worsened the reduction in GSK3β phosphorylation in mRTECs. In addition, 19 (20)-EDP was more metabolically stable than 14 (15)-EET in vivo and in vitro. Overall, these epoxide metabolites of ARA and DHA function conversely in I/R-AKI, possibly through their largely different metabolic stability and their opposite effects in modulation of H/R-caused RTEC apoptosis and GSK3β phosphorylation. This study provides AKI patients with promising therapeutic strategies and clinical cautions.


Activity of mitoxantrone in a human tumor cloning system.
We have utilized a recently developed human tumor cloning system to screen for antitumor effects in vitro of a new anthracenedione derivative, Mitoxantrone. The object was to determine if the system is useful for pinpointing the types of tumors in patients which should be studied in early Phase II clinical trials. Tumors from 267 patients were placed in culture (20 different histological tumor types). One hundred seventy tumors both grew and formed enough colonies for drug sensitivity assays. Excellent in vitro antitumor activity was noted for Mitoxantrone against human adenocarcinoma of the lung, small cell lung cancer, melanoma, and biliary tree cancer. Good antitumor activity was noted against breast cancer, ovarian cancer, non-Hodgkin's lymphoma, head and neck cancer, squamous cell lung cancer, soft tissue sarcoma, gastric cancer, and hepatomas. The drug showed no in vitro activity against colon cancer. These data indicate that Mitoxantrone has a wide spectrum of in vitro antitumor activity. A comparison of these in vitro results with the results of Phase II clinical trials with the drug should allow an evaluation of the utility of the human tumor cloning system for predicting clinical antitumor activity of a new compound.


Metabolite analyses of single cells.
Single-cell analysis is a promising method for understanding not only cellular physiology but also biological mechanisms of multicellular organisms. Although neighboring cells in multicellular organisms originate from the same genomic information, different circumstances around cells or epigenetic differences have different influences on each cell, leading to differing expression of genes, and thus differing levels and dynamics of metabolites, in single cells. However, single-cell analysis is a tough challenge, even with recent technologies, because of the small size of single cells. Unlike genes, metabolites cannot be amplified, and therefore metabolite analysis is another issue. To analyze such a tiny quantity of metabolites in a single cell, various techniques have been tried and developed. Especially in mass spectrometry, marked improvements in both detection sensitivity and ionization techniques have opened up the challenge for the analysis of metabolites in single cells. In this review, we discuss the method for metabolite detection at the level of single cells and recent advancements in technology.


Approaches to Obesity Management in Dialysis Settings: Renal Dietitian Perspectives.
Over 40% of individuals in the United States with end-stage kidney disease have obesity. Little is known about renal dietitian perspectives on obesity management in the setting of dialysis dependence. An online 21-item survey was distributed to 118 renal dietitians via individual outreach and a professional organization e-mail listserv. Four themes were explored: the burden of obesity among dialysis patients, concepts of healthy weight loss, weight loss approaches, and challenges of obesity management in dialysis settings. Respondents were asked to rank approaches and biomarkers for obesity management from 0 (least important or not used) to 100 (most important). Free text fields were provided in each category for additional comments. Thirty-one renal dietitians responded to the survey (26% response rate). The majority of respondents (90%) indicated that access to kidney transplantation was the main reason that dialysis patients with obesity desired weight loss. Calorie restriction was rated as the most common weight loss approach, and dry weight as the most important weight loss biomarker. Nearly 40% of respondents do not alter their nutritional approach when dialysis patients with obesity are losing weight, and 42% of respondents do not monitor changes in waist circumference. Exercise, diet counseling, and stress management were variably prioritized as weight loss management strategies. Barriers to obesity management in dialysis settings included lack of time, lack of training in weight loss counseling, and gaps in current renal nutritional guidelines. Despite the high prevalence of obesity among individuals with end-stage kidney disease, the results of this survey suggest that current approaches to obesity management in dialysis settings are highly variable. Many renal dietitians lack time to counsel patients on healthy weight loss strategies. Nutritional guidelines are also needed to support people with dialysis dependence and obesity who desire or require weight loss.


Severely impaired activity of lipoprotein lipase Arg243His is partially ameliorated by emulsifying phospholipids in in vitro triolein hydrolysis analysis.
Background We investigated the in vitro effects of various phospholipids as emulsifiers on the hydrolysing activities of lipoprotein lipase (LPL) Arg243His against triolein as substrate. LPL Arg243His, identified in a patient with hyperchylomicronaemia, displays severely diminished activity for triolein when emulsified with Triton X-100. Methods Lipolytic activities of plasma obtained by heparin injection from a homozygous patient with LPL Arg243His were analysed using triolein emulsified with phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylinositol (PI), lysophosphatidylcholine (LPC), or Triton X-100 as substrates. Results The hydrolysing activities of the patient's plasma for triolein emulsified with PC, PE, PS, PI, LPC and Triton X-100 were 9.22 ± 1.06 μmol/ml/h/ngLPL, 2.94 ± 1.60 μmol/ml/h/ng LPL, 3.72 ± 1.63 μmol/ml/h/ng LPL, 3.40 ± 1.20 μmol/ml/h/ngLPL, 3.72 ± 1.96 μmol/ml/h/ngLPL and 7.80 ± 4.48 μmol/ml/h/ng LPL, respectively. Thus, the specific activities of the patient's LPL determined with triolein emulsified with PC were significantly higher than those with PE, PS, PI or LPC as emulsifiers. Relative to the activities of normal plasma measured with PC, PE, PS, PI and LPC as emulsifiers, the mutant's activities were 49.1 ± 5.2%, 44.1 ± 5.7%, 31.7 ± 12.6%, 19.2 ± 6.9% and 23.8 ± 11.3%, respectively. Using PC, PE, PS, PI and LPC as emulsifiers, the mutant's activities for triolein-lipolysis relative to normal were significantly increased in comparison to the relative activity measured with the classical emulsifier, Triton X-100 (12.9 ± 6.7%). Conclusions Impaired triolein hydrolysis by LPL Arg243His was partially ameliorated by triolein emulsification with phospholipids. The in vitro analysis of triolein hydrolysis using various phospholipid emulsifiers may be useful for the further understanding of impaired LPL function.


A murine monoclonal antibody exhibiting high species specificity for Histoplasma capsulatum var. capsulatum.
A monoclonal antibody (mAb) exhibiting a high degree of species specificity for the yeast phase of the dimorphic fungus Histoplasma capsulatum was produced by a modification of the standard mAb production protocol. The technique for generating mAbs involved the use of the immunosuppressive drug cyclophosphamide to diminish the response in mice to immunodominant cross-reactive epitopes. This mAb exhibited clear specificity and did not react by ELISA with the closely related genera Blastomyces, Paracoccidioides and Sporothrix. In Western blots it recognized a linear determinant on a 70-75 kDa molecule in H. capsulatum antigen, with an extremely faint reactivity to antigens of identical molecular mass derived from Sporothrix and Paracoccidioides, and no reactivity against Blastomyces antigen.


Biohydrogen production from microalgae-Major bottlenecks and future research perspectives.
The imprudent use of fossil fuels has resulted in high greenhouse gas (GHG) emissions, leading to climate change and global warming. Reduction in GHG emissions and energy insecurity imposed by the depleting fossil fuel reserves led to the search for alternative sustainable fuels. Hydrogen is a potential alternative energy carrier and is of particular interest because hydrogen combustion releases only water. Hydrogen is also an important industrial feedstock. As an alternative energy carrier, hydrogen can be used in fuel cells for power generation. Current hydrogen production mainly relies on fossil fuels and is usually energy and CO2 -emission intensive, thus the use of fossil fuel-derived hydrogen as a carbon-free fuel source is fallacious. Biohydrogen production can be achieved via microbial methods, and the use of microalgae for hydrogen production is outstanding due to the carbon mitigating effects and the utilization of solar energy as an energy source by microalgae. This review provides comprehensive information on the mechanisms of hydrogen production by microalgae and the enzymes involved. The major challenges in the commercialization of microalgae-based photobiological hydrogen production are critically analyzed and future research perspectives are discussed. Life cycle analysis and economic assessment of hydrogen production by microalgae are also presented.


Genetic identification of microcystin ecotypes in toxic cyanobacteria of the genus Planktothrix.
Microcystins (MCs) are toxic heptapeptides which are synthesized by the filamentous cyanobacterium Planktothrix and other genera via non-ribosomal peptide synthesis. MCs share the common structure cyclo(-D-ala1-L-X2-D-erythro-beta-iso-aspartic acid3-L-Z4-adda5-D-Glu6-N-methyl-dehydroalanine7) [Adda; (2S, 3S, 8S, 9S)-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4,6-dienoic acid], in which numerous MC variants have been reported. In general, the variation in structure is due to different amino acid residues in positions 7, 2 and 4 within the MC molecule, which are thought to be activated by the adenylation domains mcyAAd1, mcyBAd1 and mcyCAd, respectively. It was the aim of the study (i) to identify MC ecotypes that differed in the production of specific MC variants and (ii) to correlate the genetic variation within adenylation domains with the observed MC variants among 17 Planktothrix strains. Comparison of the sequences of mcyAAd1 revealed two distinctive Ad-genotypes differing in base pair composition and the insertion of an N-methyl transferase (NMT) domain. The mcyAAd1 genotype with NMT (2854 bp) correlated with N-methyl-dehydroalanine and the mcyAAd1 genotype without NMT (1692 bp) correlated with dehydrobutyrine in position 7. Within mcyBAd1, a lower genetic variation (0-4 %) and an exclusive correlation between one Ad-genotype and homotyrosine as well as another Ad-genotype and arginine in position 2 was found. The sequences of mcyCAd were found to be highly similar (0-1 % dissimilarity) and all strains contained arginine in position 4. The results on adenylation domain polymorphism do provide insights into the evolutionary origin of adenylation domains in Planktothrix and may be combined with ecological research in order to provide clues about the abundance of genetically defined MC ecotypes in nature.


Metabolic interconversions of pyridoxine by Morris hepatoma No. 7777 cells. Synthesis of a novel metabolite.
The metabolic transformations of labeled pyridoxine by hepatoma cells were studied. Buffalo rats were fed ad libitum a commercially prepared pyridoxine sufficient diet for 20 days at which time they were inoculated intramuscularly with hepatoma 7777 cells in both hind leg muscles. After tumor development, 50 microCi [6-3H] pyridoxine. HCl or 5 microCi [4,5-14C] pyridoxine. HCl was injected intraperitoneally per rat. Groups of animals were subsequently sacrificed at defined time intervals up to 9 days. Vitamin B6 labeled tumor metabolites were acid extracted and separated on a muBondapak C18 column by ion pairing reverse phase high performance liquid chromatography. A novel vitamin metabolite contributing up to 28.5% of extractable radioactivity was found with retention time different than any of the known vitamin B6 compounds. Its pattern of synthesis in vivo from labeled pyridoxine was PN leads to PNP leads to PLP leads to PMP leads to X. Preliminary GC-mass spectral data suggested the unknown consisted of more than one species. This communication reports on the metabolism of vitamin B6 and the isolation, synthesis in vivo and possible significance of the novel metabolite to the economy of the tumor cells.


Utility of the Y-STR typing systems Y-PLEX 6 and Y-PLEX 5 in forensic casework and 11 Y-STR haplotype database for three major population groups in the United States.
The Y-PLEX 6 and Y-PLEX 5 systems enable analysis for 11 Y-STR loci. We present here the utility of these systems in forensic casework. A total of 188 samples, including 127 evidence samples, were analyzed using either or both of the systems. The evidence sample types included fingernail scrapings, sperm or seminal fluid, epithelial cells, blood and other tissues. The Y-STR typing systems provided useful probative results in difficult cases. A reference database for Caucasian (n = 517), African American (n = 535), and Hispanic (n = 245) population groups within the United States was generated for estimating the haplotype frequency in forensic casework. Among the individuals profiled, 311 Caucasians, 412 African Americans, and 194 Hispanics provided unique profiles in their respective population datasets. This is the first report describing the haplotype database for the set of 11 Y-STR loci recommended by the Scientific Working Group on DNA Analysis Methods (SWGDAM). Linkage analysis reveals that the frequencies from forensically important autosomal loci can be multiplied with the Y-STR haplotype frequency. The results from Y-PLEX systems have been accepted in courts in the United States.


Corticosteroid treatment and intensive insulin therapy for septic shock in adults: a randomized controlled trial.
Corticosteroid therapy induces potentially detrimental hyperglycemia in septic shock. In addition, the benefit of adding fludrocortisone in this setting is unclear. To test the efficacy of intensive insulin therapy in patients whose septic shock was treated with hydrocortisone and to assess, as a secondary objective, the benefit of fludrocortisone. A multicenter, 2 x 2 factorial, randomized trial, involving 509 adults with septic shock who presented with multiple organ dysfunction, as defined by a Sequential Organ Failure Assessment score of 8 or more, and who had received hydrocortisone treatment was conducted from January 2006 to January 2009 in 11 intensive care units in France. Patients were randomly assigned to 1 of 4 groups: continuous intravenous insulin infusion with hydrocortisone alone, continuous intravenous insulin infusion with hydrocortisone plus fludrocortisone, conventional insulin therapy with hydrocortisone alone, or conventional insulin therapy with intravenous hydrocortisone plus fludrocortisone. Hydrocortisone was administered in a 50-mg bolus every 6 hours, and fludrocortisone was administered orally in 50-microg tablets once a day, each for 7 days. In-hospital mortality. Of the 255 patients treated with intensive insulin, 117 (45.9%), and 109 of 254 (42.9%) treated with conventional insulin therapy died (relative risk [RR], 1.07; 95% confidence interval [CI], 0.88-1.30; P = .50). Patients treated with intensive insulin experienced significantly more episodes of severe hypoglycemia (<40 mg/dL) than those in the conventional-treatment group, with a difference in mean number of episodes per patient of 0.15 (95% CI, 0.02-0.28; P = .003). At hospital discharge, 105 of 245 patients treated with fludrocortisone (42.9%) died and 121 of 264 (45.8%) in the control group died (RR, 0.94; 95% CI, 0.77-1.14; P = .50). Compared with conventional insulin therapy, intensive insulin therapy did not improve in-hospital mortality among patients who were treated with hydrocortisone for septic shock. The addition of oral fludrocortisone did not result in a statistically significant improvement in in-hospital mortality. clinicaltrials.gov Identifier: NCT00320099.


Haplotype-specific sequence encoding the protein kinase, interferon-inducible double-stranded RNA-dependent activator in the human leukocyte antigen class II region.
The protein kinase, interferon-inducible double-stranded (ds)RNA-dependent activator (PRKRA) is a dsRNA-binding protein which activates a protein kinase participating in the antiviral activity of interferon. Our previous studies indicated that the nucleotide sequence encoding PRKRA, which appeared to be an intronless gene, was present in PAC HS265J14 containing the human leukocyte antigen (HLA) DR subregion. In this study, we further investigated and characterized the PRKRA gene on the human genome by means of Southern blotting and polymerase chain reaction with homozygous typing cell lines for HLA genes. Results indicated that the presence of PRKRA in the DR subregion was dependent on the DR53 group. Consistently, fluorescence in situ hybridization profiles with PRKRA as a probe showed that the hybridization signal on Chromosome (Chr) 6p21.3 was seen only in the samples carrying the DR haplotypes that belonged to the DR53 group. Interestingly, another hybridization signal, which was mapped on Chr 2q31.2-q32.1, was always detected in the samples examined, i.e., even in the samples negative for the DR53 group. The outcome of a sequence-database homology search further indicated that the PRKRA gene with introns appeared to be present in a recently opened draft-sequence, RP11-65L3 (GenBank accession number AC009948), which is located between D2S335 and D2S2257. Together, the data presented here indicate that the PRKRA gene in the DR subregion is a processed pseudogene (PRKRApsi), which could have been generated only on the DR53 common ancestor's genome, and that the master copy of PRKRApsi is most probably present on Chr 2q31.2-q32.1.


In silico optimization of pharmacokinetic properties and receptor binding affinity simultaneously: a 'parallel progression approach to drug design' applied to β-blockers.
The present work exploits the potential of in silico approaches for minimizing attrition of leads in the later stages of drug development. We propose a theoretical approach, wherein 'parallel' information is generated to simultaneously optimize the pharmacokinetics (PK) and pharmacodynamics (PD) of lead candidates. β-blockers, though in use for many years, have suboptimal PKs; hence are an ideal test series for the 'parallel progression approach'. This approach utilizes molecular modeling tools viz. hologram quantitative structure activity relationships, homology modeling, docking, predictive metabolism, and toxicity models. Validated models have been developed for PK parameters such as volume of distribution (log Vd) and clearance (log Cl), which together influence the half-life (t1/2) of a drug. Simultaneously, models for PD in terms of inhibition constant pKi have been developed. Thus, PK and PD properties of β-blockers were concurrently analyzed and after iterative cycling, modifications were proposed that lead to compounds with optimized PK and PD. We report some of the resultant re-engineered β-blockers with improved half-lives and pKi values comparable with marketed β-blockers. These were further analyzed by the docking studies to evaluate their binding poses. Finally, metabolic and toxicological assessment of these molecules was done through in silico methods. The strategy proposed herein has potential universal applicability, and can be used in any drug discovery scenario; provided that the data used is consistent in terms of experimental conditions, endpoints, and methods employed. Thus the 'parallel progression approach' helps to simultaneously fine-tune various properties of the drug and would be an invaluable tool during the drug development process.


Cerebrospinal Fluid Analysis With the BioFire FilmArray Meningitis/Encephalitis Molecular Panel Reduces Length of Hospital Stay in Patients With Suspected Central Nervous System Infections.
The Meningitis/Encephalitis Panel (MEP) is a sensitive and specific Food and Drug Administration-approved molecular diagnostic test for the 14 most common infectious etiologies of meningoencephalitis. Using a before-after controlled study design, MEP reduced length of hospital stay by 1.5 days, and this effect was mediated by the reduced time to final microbiology reporting.


Glucocorticoids promote the proliferation and antagonize the retinoic acid-mediated growth suppression of Epstein-Barr virus-immortalized B lymphocytes.
Glucocorticoids are able to release Epstein-Barr virus-immortalized (EBV-immortalized) lymphoblastoid B cell lines (LCLs) from the persistent growth arrest induced in these cells by retinoic acid (RA). Moreover, physiologic concentrations of glucocorticoids efficiently antagonized LCL growth inhibition induced by 13-cis-RA; 9-cis-RA; all-trans-RA; and Ro 40-6055, an RA alpha receptor (RAR alpha) selective agonist. RAR alpha expression levels, however, were not affected by glucocorticoids. Glucocorticoids, but not other steroid hormones, directly promote LCL proliferation, a phenomenon that was mainly mediated by down-regulation of the cyclin-dependent kinase (CDK) inhibitor p27(Kip-1). Moreover, glucocorticoids contrasted the up-regulation of p27(Kip-1), which was underlying the RA-induced LCL growth arrest, thereby indicating that glucocorticoids and RA signalings probably converge on p27(Kip-1). Both antagonism of RA-mediated growth inhibition and promotion of LCL proliferation were efficiently reversed by the glucocorticoid receptor (GR) antagonist RU486, indicating that all of these effects were mediated by GR. Of note, RU486 also proved to be effective in vivo and, in mice, was able to significantly inhibit the growth of untreated LCLs as well as LCLs growth-arrested by RA in vitro. These findings provide a rational background to further evaluate the possible role of glucocorticoids in the pathogenesis of EBV-related lymphoproliferations of immunosuppressed patients. Moreover, GR antagonists deserve further consideration for their possible efficacy in the management of these disorders, and the use of schedules, including both RA and a GR antagonist, may allow a more thorough evaluation of the therapeutic potential of RA in this setting. (Blood. 2000;96:711-718)


Analysis of postmarket complaints database for the iFuse SI Joint Fusion System®: a minimally invasive treatment for degenerative sacroiliitis and sacroiliac joint disruption.
The sacroiliac joint is a common but under-recognized source of low back and gluteal pain. Patients with degenerative sacroiliitis or sacroiliac joint disruption resistant to nonsurgical treatments may undergo open surgery with sacroiliac joint arthrodesis, although outcomes are mixed and risks are significant. Minimally invasive sacroiliac joint arthrodesis was developed to minimize the risk of iatrogenic injury and to improve patient outcomes compared with open surgery. Between April 2009 and January 2013, 5319 patients were treated with the iFuse SI Joint Fusion System® for conditions including sacroiliac joint disruption and degenerative sacroiliitis. A database was prospectively developed to record all complaints reported to the manufacturer in patients treated with the iFuse device. Complaints were collected through spontaneous reporting mechanisms in support of ongoing mandatory postmarket surveillance efforts. Complaints were reported in 204 (3.8%) patients treated with the iFuse system. Pain was the most commonly reported clinical complaint (n = 119, 2.2%), with nerve impingement (n = 48, 0.9%) and recurrent sacroiliac joint pain (n = 43, 0.8%) most frequently cited. All other clinical complaints were rare (≤0.2%). Ninety-six revision surgeries were performed in 94 (1.8%) patients at a median follow-up of four (range 0-30) months. Revisions were typically performed in the early postoperative period for treatment of a symptomatic malpositioned implant (n = 46, 0.9%) or to correct an improperly sized implant in an asymptomatic patient (n = 10, 0.2%). Revisions in the late postoperative period were performed to treat symptom recurrence (n = 34, 0.6%) or for continued pain of undetermined etiology (n = 6, 0.1%). Analysis of a postmarket product complaints database demonstrates an overall low risk of complaints with the iFuse SI Joint Fusion System in patients with degenerative sacroiliitis or sacroiliac joint disruption.


Structural analysis and evaluation of the 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) gene in human essential hypertension.
Mutations of the 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) gene cause the syndrome of apparent mineralocorticoid excess, a rare autosomal recessive form of hypertension. We therefore investigated the question of whether variants of the 11beta-HSD2 gene can contribute to genetic susceptibility to essential hypertension. We performed a linkage study in 162 French hypertensive sibships using the affected sib-pair method on 347 sibling pairs and a polymorphic microsatellite marker that we identified in a 30 kb cosmid clone containing the 11beta-HSD2 gene. The coding sequence, introns 2-4 and 350 bp of the 5'-flanking region of the 11beta-HSD2 gene were screened for polymorphisms by polymerase chain reaction/single-strand conformation polymorphism, and a single polymorphism, Glu178/Glu (G534A), was identified in exon 3, which did not change the encoded amino acid sequence. A case-control study was conducted on 370 hypertensive subjects with a positive family history of hypertension and 783 French subjects with hypertension with or without a family history of hypertension, compared with 313 normotensive control subjects, all of whom were analyzed for the newly identified bi-allelic polymorphism. Statistical analyses using the affected sib-pair method did not show significant linkage between the 11beta-HSD2 microsatellite marker and hypertension. Furthermore, no positive association with hypertension was found with the Glu178/Glu (G534A) polymorphism. Our data do not suggest that variants of the 11beta-HSD2 gene contribute substantially to essential hypertension in Caucasians.


Relationship between dynamic electrocardiogram and CRP, IL-6, ET-1 expression in myocardial ischemia patients with coronary heart disease.
This study aimed to observe the relationship between dynamic electrocardiogram and CRP, IL-6, and ET-1 expression in individuals with myocardial ischemia and Coronary Heart Disease (CHD). For this purpose, from January 2021 to December 2022, 80 patients with CHD were admitted to the hospital to determine the presence of myocardial ischemia according to coronary angiography. The individuals were separated into a myocardial ischemia group and a no myocardial ischemia group. Dynamic electrocardiogram (DCG), serum CRP, IL-6, and ET-1 were used in the two groups, respectively. The association between dynamic electrocardiogram indexes and serum CRP, IL-6, and ET-1 levels was discovered using a Pearson correlation analysis. Results showed that the SDNN, SDANNI, rMSSD and PNN50 of Patients with Myocardial Ischemia (PWMI) were lower than individuals with CHD without myocardial ischemia (P<0.05). CRP and IL-6 were negatively correlated with SDNN, SDANNI, rMSSD and PNN50 (P<0.001). ET-1 had a bad relationship with rMSSD and PNN50 (P<0.001). Correlation heat map analysis showed that the color difference of IL-6 was the most obvious between PWMI and Patients Without Myocardial Ischemia (POMI), and IL-6 was more strongly correlated with dynamic electrocardiogram-related indexes of myocardial ischemia. In individuals with CHD myocardial ischemia, there is a negative connection between the DCG index and the production of the inflammatory cytokines CRP, IL-6, and ET-1. In conclusion, CRP, IL-6, and ET-1 levels should be monitored in patients with decreased heart rate variability, so as to further determine the level of micro-inflammation and endothelial function.


Synthesis of 5-substituted aminomethyluracils via the Mannich reaction.
An extension of the Mannich reaction, in which aminomethylation of the five position of uracil, is reported. Thus, primary and secondary alkylamines and primary aromatic amines containing ring-activating groups led to the title compounds 3-10. Compound 11 in which the aromatic ring contains the ring-deactivating nitro group was synthesized in an alternative way. All compounds were characterized by their elemental and spectral properties.


Costs of outpatients with fecal incontinence.
Fecal incontinence is a problem with a high prevalence. Patients generally suffer from their problems for many years. It has been shown that quality of life is negatively affected but health economic data for fecal incontinence are limited. The aim of this study was to estimate the costs associated with fecal incontinence in a large outpatient study group, taking a societal perspective. Based on questionnaire data, we calculated the costs of health-care resources, out-of-pocket expenses and costs associated with production losses in paid and unpaid work. Data were available for 253 patients, of which 228 (90%) were female and 209 (83%) were treated in an academic medical center. The mean age of patients was 59 years (SD+/-13) with a mean duration of incontinence of 8.5 years (SD+/-8.3). Total costs were estimated on C2169 per fecal incontinent patient per year. Production losses in paid and unpaid work accounted for more than half of the total costs and costs of health-care visits accounted for almost a fifth of total costs. Costs associated with protective material (partially reimbursable and not reimbursable) formed only one-tenth of total costs, while incontinence medication was responsible for only 5% of total costs. More than half of total costs of fecal incontinence are made up of indirect non-medical costs. The costs associated with the use of incontinence material and other personal expenses are limited.


From Telson to Attack in Mantis Shrimp: Bridging Biomechanics and Behavior in Crustacean Contests.
In the spirit of this symposium on the physical mechanisms of behavior, we review mantis shrimp ritualized fighting, from the telson to the attack, as an inspiring example of how the integration of biomechanics and behavioral research can yield a penetrating narrative for how animals accomplish important activities, including agonistic actions. Resolving conflicts with conspecifics over valuable resources is an essential task for animals, and this takes an unusual form in mantis shrimp due to their powerful raptorial appendages. Decades of field and laboratory research have provided key insights into the natural agonistic interactions of diverse mantis shrimp species, including how they use their raptorial weapons against one another in telson sparring matches over cavities. These insights provided the foundation for functional morphologists, biomechanists, and engineers to work through different levels of organization: from the kinematics of how the appendages move to the elastic mechanisms that power the strike, and down to the structure, composition, and material properties that transmit and protect against high-impact forces. Completing this narrative are studies on the defensive telson and how this structure is biomechanically matched to the weapon and the role it plays in ritualized fighting. The biomechanical understanding of the weapon and defense in mantis shrimp has, in turn, enabled a better understanding of whether mantis shrimp assess one another during contests and encouraged questions of evolutionary drivers on both the arsenal and behavior. Altogether, the body of research focused on mantis shrimp has presented perhaps the most comprehensive understanding of fighting, weapons, and defenses among crustaceans, from morphology and biomechanics to behavior and evolution. While this multi-level analysis of ritualized fighting in mantis shrimp is comprehensive, we implore the need to include additional levels of analysis to obtain a truly holistic understanding of this and other crustacean agonistic interactions. Specifically, both molting and environmental conditions are often missing from the narrative, yet they greatly affect crustacean weapons, defenses, and behavior. Applying this approach more broadly would generate a similarly profound understanding of how crustaceans carry out a variety of important tasks in diverse habitats.


Increasing involvement of CAPN1 variants in spastic ataxias and phenotype-genotype correlations.
Spastic ataxias are rare neurogenetic disorders involving spinocerebellar and pyramidal tracts. Many genes are involved. Among them, CAPN1, when mutated, is responsible for a complex inherited form of spastic paraplegia (SPG76). We report the largest published series of 21 novel patients with nine new CAPN1 disease-causing variants and their clinical characteristics from two European university hospitals (Paris and Stockholm). After a formal clinical examination, causative variants were identified by next-generation sequencing and confirmed by Sanger sequencing. CAPN1 variants are a rare cause (~ 1.4%) of young-adult-onset spastic ataxia; however, together with all published cases, they allowed us to better describe the clinical and genetic spectra of this form. Truncating variants are the most frequent, and missense variants lead to earlier age at onset in favor of an additional deleterious effect. Cerebellar ataxia with cerebellar atrophy, dysarthria and lower limb weakness are often associated with spasticity. We also suggest that cognitive impairment and depression should be assessed specifically in the follow-up of SPG76 cases.


Factors underlying denial of and disbelief in COVID-19.
To investigate factors that influence or promote disbelief and negative attitudes toward COVID-19. This was cross-sectional study involving 544 males and females ≥ 18 years of age in Greece between December of 2020 and January of 2021. All participants were informed about the purpose of the study, protection of anonymity, and volunteer participation. Participants completed an online anonymous 40-item questionnaire. Analysis of data included the identification of correlations and use of t-tests and ANOVA. The level of knowledge regarding COVID-19 transmission routes, manifestations, and prevention was high in our sample. Women appeared to have a more positive attitude toward COVID-19 prevention and management than did men (p = 0.032 and p = 0.018, respectively). Younger people (18-30 years of age) seemed to deny the validity of scientific data and mass media reports about ways to deal with the pandemic more commonly than did those > 30 years of age (p = 0.003 and p = 0.001, respectively). People who resided in cities more commonly believed in scientific announcements than did those living in villages (p = 0.029). In order to minimize cases of denial of and disbelief in COVID-19 and to promote vaccination, a series of actions are required. Governments should implement a series of measures to contain the disease, taking into consideration the psychological and social aspects of those policies.


Ice thickness measurements by Raman scattering.
A compact Raman LIDAR system with a spectrograph was used for express ice thickness measurements. The difference between the Raman spectra of ice and liquid water is employed to locate the ice-water interface while elastic scattering was used for air--ice surface detection. This approach yields an error of only 2 mm for an 80 mm thick ice sample, indicating that it is a promising express noncontact thickness measurements technique in field experiments.


Reliability and psychometric validity of Hindi version of Depression, Anxiety and Stress Scale-21 (DASS-21) for Hindi speaking Head Neck Cancer and Oral Potentially Malignant Disorders Patients.
The aim of the present study was to carefully translate and psychometrically validate the depression, anxiety, and stress scale-21 (DASS-21) in Hindi language for Hindi-speaking head and neck cancer (HNC) and oral potentially malignant disorder (OPMD) patients. One hundred and sixty-seven HNC and OPMD patients were recruited for this study comprising of 111 oral cancer and 56 OPMD patients. According to internationally accepted guidelines, forward and backward translation procedures were performed, to develop a culturally acceptable version of DASS-21. Validated Hindi version of hospital anxiety and depression scale (HADS) questionnaire was used to compare the scores. Internal consistency for construct validity of the DASS-21 was assessed. Related data and the patients' demographics details were recorded. Factor analysis using varimax rotation was also carried out. The Cronbach's alpha values were 0.998, 0.990, and 0.994, respectively, for depression, anxiety, and stress domains, which was comparable to other studies and indicated a strong internal consistency and good construct validity. Factor and varimax analysis revealed items to be well suited to their respective domains. A statistically significant strong correlation was reflected with HADS Hindi questionnaire; Spearman's rank correlation values observed were 0.80 and 0.83 for depression and anxiety, respectively. Hindi version of the DASS-21 questionnaire appears to be culturally appropriate, reliable, and psychometrically valid tool for evaluation of the psychological burden (depression, anxiety, and stress) in Hindi-speaking HNC and OPMD patients.


Determinants of prompt and adequate care among presumed malaria cases in a community in eastern Rwanda: a cross sectional study.
In order to understand factors influencing fever/malaria management practices among community-based individuals, the study evaluated psychosocial, socio-demographic and environmental determinants of prompt and adequate healthcare-seeking behaviours. A quantitative household (HH) survey was conducted from December 2014 to February 2015 in Ruhuha sector, Bugesera district in the Eastern province of Rwanda. HHs that reported having had at least one member who experienced a fever and/or malaria episode in the previous 3 months prior to the study were included in the analysis. Healthcare-seeking behaviours associated with the last episode of illness were analysed. Socio-demographic, health facility access, long-lasting insecticidal-treated nets (LLINs), data on malaria knowledge, data and theory of planned behaviour (TPB) related variables (attitudes, subjective norms, perceived behavioural control) with regard to fever/malaria healthcare seeking, were collected. The primary outcome was prompt and adequate care defined as: (1) seeking advice or treatment at a health facility (health centre or hospital) or from a community health worker (CHW); (2) advice or treatment seeking within same/next day of symptoms onset; (3) received a laboratory diagnosis; (4) received advice or treatment; and, (5) reported completing the prescribed dose of medication. Determinants of prompt and adequate care among presumed malaria cases were evaluated using a logistic regression analysis. Overall, 302 (21 %) of the 1410 interviewed HHs reported at least one member as having experienced a fever or malaria within the 3 months prior to the survey. The number of HHs (where at least one member reported fever/malaria) that reported seeking advice or treatment at a health facility (health centre or hospital) or from a CHW was 249 (82.4 %). Of those who sought advice or treatment, 87.3 % had done so on same/next day of symptoms developing, 82.8 % received a laboratory diagnosis, and more than 90 % who received treatment reported completing the prescribed dosage. Prompt and adequate care was reported from 162 of the 302 HHs (53.6 %) that experienced fever or malaria for one or more HH members. Bivariate analyses showed that head of household (HoH)-related characteristics including reported knowledge of three or more malaria symptoms, having health insurance, being able to pay for medical services, use of LLINs the night before the survey, having a positive attitude, perceiving social support, as well as a high-perceived behavioural control with regard to healthcare seeking, were all significantly associated with prompt and adequate care. In the final logistic regression model, a high-perceived behavioural control (odds ratio (OR) 5.068, p = 0.042), having a health insurance (OR 2.410, p = 0.044) and having knowledge of malaria symptoms (OR 1.654, p = 0.049) significantly predicted prompt and adequate care. To promote prompt and adequate care seeking for malaria in the area, particular emphasis should be placed on community-focused strategies that promote early malaria symptom recognition, increased health insurance coverage and enhanced perceived behavioural control with regard to healthcare-seeking.


Effects of kinesio taping to the quadriceps femoris muscles on functions of elderly women.
[Purpose] The purpose of this study is to investigate effects of kinesio taping to the quadriceps femoris on functions of elderly women. [Subjects and Methods] The subjects of this study were 22 elderly women with osteoarthritis, who were divided into two groups of a general exercise group 12 elderly and a kinesiology taping group 12 elderly. Two groups underwent a 30-min exercise for strengthening the lower limb muscles three times per week for four weeks. After the exercise, the kinesiology taping group was treated by the kinesio taping. Kinesio tapes were attached to the quadriceps femoris, three times per week for four weeks. The Korean Western Ontario and McMaster Universities Osteoarthritis Index, sit to standing, and Time up & Go test were used for assessment before and after the intervention. [Results] As a result, the kinesiology taping group showed significant differences in the Korean Western Ontario and McMaster Universities Osteoarthritis Index, sit to standing, and Time up & Go test between pre- and post-intervention, while the general exercise group showed no significant differences in pre- and post-intervention. There was a significant difference in between-group comparison. [Conclusion] The kinesio taping for the quadriceps femoris was effective on improving functions of elderly women with osteoarthritis.


Selection signature analysis implicates the PC1/PCSK1 region for chicken abdominal fat content.
We conducted a selection signature analysis using the chicken 60k SNP chip in two chicken lines that had been divergently selected for abdominal fat content (AFC) for 11 generations. The selection signature analysis used multiple signals of selection, including long-range allele frequency differences between the lean and fat lines, long-range heterozygosity changes, linkage disequilibrium, haplotype frequencies, and extended haplotype homozygosity. Multiple signals of selection identified ten signatures on chromosomes 1, 2, 4, 5, 11, 15, 20, 26 and Z. The 0.73 Mb PC1/PCSK1 region of the Z chromosome at 55.43-56.16 Mb was the most heavily selected region. This region had 26 SNP markers and seven genes, Mar-03, SLC12A2, FBN2, ERAP1, CAST, PC1/PCSK1 and ELL2, where PC1/PCSK1 are the chicken/human names for the same gene. The lean and fat lines had two main haplotypes with completely opposite SNP alleles for the 26 SNP markers and were virtually line-specific, and had a recombinant haplotype with nearly equal frequency (0.193 and 0.196) in both lines. Other haplotypes in this region had negligible frequencies. Nine other regions with selection signatures were PAH-IGF1, TRPC4, GJD4-CCNY, NDST4, NOVA1, GALNT9, the ESRP2-GALR1 region with five genes, the SYCP2-CADH4 with six genes, and the TULP1-KIF21B with 14 genes. Genome-wide association analysis showed that nearly all regions with evidence of selection signature had SNP effects with genome-wide significance (P<10(-6)) on abdominal fat weight and percentage. The results of this study provide specific gene targets for the control of chicken AFC and a potential model of AFC in human obesity.


Pilot evaluation of sensitive data segmentation technology for privacy.
Consent2Share (C2S) is an open source software created by the Office of the National Coordinator Data Segmentation for Privacy initiative to support electronic health record (EHR) granular segmentation. To date, there are no published formal evaluations of Consent2Share. Structured data (e.g. medications) codified using standard clinical terminologies (e.g. RxNorm) was extracted from the EHR of 36 patients with behavioral health conditions from study sites. EHRs were available through a health information exchange and two sites. The EHR data was already classified into data types (e.g. procedures and services). Both Consent2Share and health providers classified EHR data based on value sets (e.g. mental health) and sensitivity (e.g. not sensitive. Descriptive statistics and Chi-square analysis were used to compare differences between data categorizations. From the resulting 1,080 medical records items, 584 were distinct. Significant differences were found between sensitivity classifications by Consent2Share and providers (χ2 (2, N = 584) = 114.74, p = <0.0001). Sensitivity comparisons led to 56.0 % of agreements, 31.2 % disagreements, and 12.8 % partial agreements. Most (97.8 %) disagreements resulted from information classified as not sensitive by Consent2Share, but sensitive by provider (e.g. behavioral health prevention education service). In terms of data types, most disagreements (57.1 %) focused on procedures and services information (e.g. ligation of fallopian tube). When considering value sets, most disagreements focused on genetic data (100.0 %), followed by sexual and reproductive health (88.9 %). There is a need to further validate Consent2Share before broad use in health care settings. The outcomes from this pilot study will help guide improvements in segmentation logic of tools like Consent2Share and may set the stage for a new generation of personalized consent engines.