Effect of Y-24180, an antagonist at platelet-activating factor (PAF) receptors, on IgE-mediated cutaneous reactions in mice.
We examined the effect of Y-24180, a potent platelet-activating factor (PAF) antagonist, on IgE-mediated cutaneous reactions in mice. Female BALB/c mice were used. Drugs were orally administered 1 h before a dinitrofluorobenzene (DNFB) challenge or 1 h before and 12 h after the challenge. Biphasic increase in ear thickness, with peak responses at 1 h (immediate phase reaction, IPR) and 24 h (late phase reaction, LPR) after the DNFB challenge, were induced in mice which had been passively sensitized with monoclonal anti-dinitrophenyl IgE antibody 24 h before the DNFB challenge. Ear thickness was measured with a dial thickness gauge. Y-24180, WEB2086, ketotifen, and suplatast suppressed the IPR. Y-24180 also suppressed the LPR when administered once at 10 mg/kg or twice at 1 to 10 mg/kg. WEB2086 suppressed the LPR only when administered twice. However, ketotifen and suplatast did not suppress the LPR even when administered twice. Single administration of prednisolone significantly suppressed both the IPR and LPR. These results indicate that PAF may be involved in the induction of biphasic cutaneous reactions mediated by IgE, and Y-24180 is more effective compared with WEB2086 in this model. It is possible that the difference in the effectiveness between Y-24180 and WEB2086 depends on the persistence of those activities.


Significant gut microbiota related to patterns of drinking and alcohol relapse in patients with alcoholic hepatitis undergoing stool transplant or corticosteroid therapy.
Alcohol-induced gut microbiota (GM) alterations are linked to alcohol use disorder (AUD) pathogenesis. Healthy donor stool transplant (fecal microbiota transplant [FMT]) reduced alcohol desire and improved clinical outcomes in small animal and human studies. Baseline and post-therapy-related GM changes in a real-world cohort with severe alcohol-related liver disease and AUD, patterns of drinking, and relapse have not been studied. We prospectively analyzed retrospective clinical data and stored samples to examine GM alterations in a cohort of severe alcohol-associated hepatitis (SAH) patients who underwent FMT or corticosteroid treatment followed for at least 12 months. The GM changes at baseline in the context of a pattern of drinking (binge vs. every day) and baseline and post-treatment alcohol relapse status (relapser vs. non-relapser). We identified 28 patients on FMT and 25 on corticosteroids who survived 1 year post-treatment. After necessary exclusions, the final cohort for various grouped GM analysis included 16 patients in the FMT arm and 14 on corticosteroids. Pedobacter and Streptophyta species at the commencement of treatment predicted alcohol relapse in steroid-ineligible patients receiving FMT and steroid-treated patients, respectively. At 6-12 months post-FMT, non-relapsers had elevated short-chain fatty acid-producing bacterial taxa linked with lower alcohol cravings. Alcohol relapse was significantly more in those on steroid therapy and was associated with the upregulation of the nucleotide metabolism pathway related to ethanol metabolism. We demonstrate pertinent baseline and post-treatment intestinal bacterial alterations that impact patterns of AUD patterns and relapse in SAH patients in the context of the therapy offered.


Hinge stiffness is a barrier to RNA folding.
Cation-mediated RNA folding from extended to compact, biologically active conformations relies on a temporal balance of forces. The Mg2 +-mediated folding of the Tetrahymena thermophila ribozyme is characterized by rapid nonspecific collapse followed by tertiary-contact-induced compaction. This article focuses on an autonomously folding portion of the Tetrahymena ribozyme, its P4-P6 domain, in order to probe one facet of the rapid collapse: chain flexibility. The time evolution of P4-P6 folding was followed by global and local measures as a function of Mg2 + concentration. While all concentrations of Mg2 + studied are sufficient to screen the charge on the helices, the rates of compaction and tertiary contact formation diverge as the concentration of Mg2 + increases; collapse is greatly accelerated by Mg2 +, while tertiary contact formation is not. These studies highlight the importance of chain stiffness to RNA folding; at 10 mM Mg2 +, a stiff hinge limits the rate of P4-P6 folding. At higher magnesium concentrations, the rate-limiting step shifts from hinge bending to tertiary contact formati


A gene encoding an acyl hydrolase is involved in leaf senescence in Arabidopsis.
SAG101, a leaf senescence-associated gene, was cloned from an Arabidopsis leaf senescence enhancer trap line and functionally characterized. Reporter gene and RNA gel blot analyses revealed that SAG101 was not expressed until the onset of senescence in leaves. A recombinant SAG101 fusion protein overexpressed in Escherichia coli displayed acyl hydrolase activity. Antisense RNA interference in transgenic plants delayed the onset of leaf senescence for approximately 4 days. Chemically induced overexpression of SAG101 caused precocious senescence in both attached and detached leaves of transgenic Arabidopsis plants. These data suggest that SAG101 plays a significant role in leaf senescence.


The potential for carbon bio-sequestration in China's paddy rice (Oryza sativa L.) as impacted by slag-based silicate fertilizer.
Rice is a typical silicon-accumulating plant. Silicon (Si), deposited as phytoliths during plant growth, has been shown to occlude organic carbon, which may prove to have significant effects on the biogeochemical sequestration of atmospheric CO2. This study evaluated the effects of silicate fertilization on plant Si uptake and carbon bio-sequestration in field trials on China's paddy soils. The results showed (1) Increased Si concentrations in rice straw with increasing application rates of silicate fertilizer; (2) Strong positive correlations between phytolith contents and straw SiO2 contents and between phytolith contents and phytolith-occluded carbon (PhytOC) contents in rice straw; (3) Positive correlations between the phytolith production flux and either the above-ground net primary productivity (ANPP) or the PhytOC production rates; (4) Increased plant PhytOC storage with increasing application rates of silicate fertilizer. The average above-ground PhytOC production rates during China's rice production are estimated at 0.94 × 10(6) tonnes CO2 yr(-1) without silicate fertilizer additions. However, the potential exists to increase PhytOC levels to 1.16-2.17 × 10(6) tonnes CO2 yr(-1) with silicate fertilizer additions. Therefore, providing silicate fertilizer during rice production may serve as an effective tool in improving atmospheric CO2 sequestration in global rice production areas.


Albumin displacement at the air-water interface by Tween (Polysorbate) surfactants.
Tween (polysorbate) 20 and 80 are surfactants used for the development of parenteral protein drugs, due to their beneficial safety profile and stabilisation properties. To elucidate the mechanism by which Tween 20 and 80 stabilise proteins in aqueous solutions, either by a "direct" protein to surfactant interaction and/or by an interaction with the protein film at the air-water interface, we used spectroscopic (Infrared Reflection Absorption Spectroscopy, IRRAS) and microscopic techniques (Brewster Angle Microscopy, BAM) in combination with surface pressure measurements. To this end, the impact of both types of Tweens with regard to the displacement of the protein from the air-water interface was studied. As a model protein, human serum albumin (HSA) was used. The results for the displacement of the adsorbed HSA films by Tweens 20 and 80 can partially be understood on the basis of an orogenic displacement mechanism, which depends on the critical surface pressure of the adsorbed protein film. With increasing concentration of Tween in the sub-phase, BAM images showed the formation of different domain morphologies. IRRA-spectra supported the finding that at high protein concentration in the sub-phase, the protein film could not be completely displaced by the surfactants. Comparing the impact of both surfactants, we found that Tween 20 adsorbed faster to the protein film than Tween 80. The adsorption kinetics of both Tweens and the speed of protein displacement increased with rising surfactant concentration. Tween 80 reached significant lower surface pressures than Tween 20, which led to an incomplete displacement of the observed HSA film.


The micron stroke hypothesis of Alzheimer's disease and dementia.
Alzheimer's disease as currently described in the medical literature is often more a description of dementia rather than a specific disease. In over a century of scientific work there has been no proven theory as to the precise pathogenesis of Alzheimer's disease and dementia. As there is no efficient treatment for patients with Alzheimer's disease, prevention or attenuation of the disease is of substantial value. An intricate collection of hypotheses, studies, research, and experience has made it complicated for one to completely understand this disease. The purpose of this hypothesis is to illustrate new concepts and work to link those concepts to the present understanding of an obscure disease. The search for a single unifying hypothesis on the etiology of Alzheimer's disease has been elusive. Many hypotheses associated to Alzheimer's disease have not survived their testing to become theory. Suggested here is that the elusive nature of etiology of dementia is not from one cause, but rather the causes are numerous. Medical terminology used freely for decades is rarely evaluated in the light of a new hypothesis. At the foundation of this work is the suggestion of a new medical term: Micron Strokes. The Micron Stroke Hypothesis of Alzheimer's Disease and Dementia include primary and secondary factors. The primary factors can be briefly described as baseline brain tissue, atrial fibrillation, hypercoaguable state, LDL, carotid artery stenosis, tobacco exposure, hypertension diabetes mellitus, and the presence of systemic inflammation. Dozens of secondary factors contribute to the development of dementia. Most dementia is caused by nine primary categories of factors as they interact to cause micron strokes to the brain.


The impact of infection control cost reimbursement policy on central line-associated bloodstream infections.
In September 2016, the Korean National Health Insurance Service began reimbursing infection control (IC) costs on the condition that a certain number of doctors and full-time nurses for IC be allocated to supported hospitals. We analyzed the impact of the IC cost reimbursement policy on central line-associated bloodstream infections (CLABSIs). A before-and-after study that analyzed the CLABSI rate trends between preintervention (January 2016 to February 2017) and intervention (March to December 2017) periods using autoregression time series analysis was performed in intensive care units (ICUs) at a 750-bed, secondary care hospital in Daegu, Republic of Korea. The enhanced IC team visited ICUs daily, monitored the implementation of CLABSI prevention bundles, and educated all personnel involved in catheter insertion and maintenance from March 2017. Autoregressive analysis revealed that the CLABSI rates per month in the preintervention and intervention periods were -0.256 (95% confidence interval, -0.613 to 0.101; P = .15) and -0.602 (95% confidence interval, -0.972 to -0.232; P = .008), respectively. The rates of compliance with maximal barrier precautions significantly improved from the preintervention (36.2%) to the intervention (77.9%) period (χ² test, P < .001). The IC cost reimbursement policy accelerated the decline in CLABSI rates significantly in monitored ICUs. A nationwide study to evaluate the effectiveness of the IC cost reimbursement policy for various health care-associated infections is warranted.


Identification of a new HLA-G allele, HLA-G*01:19, by cloning and phasing.
A new HLA-G allelic variant, HLA-G*01:19, was identified in a southern Chinese Han population by polymerase chain reaction-sequence-based typing (PCR-SBT), cloning and phasing. HLA-G*01:19 differs from HLA-G*01:04:01 by a nonsynonymous cytosine at position 99 in exon 2, resulting in amino acid change from valine to leucine at codon 34 of the mature HLA-G molecule.


Outcomes following lung re-transplantation in patients with cystic fibrosis.
We examined cystic fibrosis (CF) patients and compared their clinical status at the time of primary versus double lung re-transplantation (re-DLTx) in order to better understand lung retransplant practice patterns. We performed a retrospective analysis of the UNOS Database identifying CF patients ≥18 years old undergoing re-DLTx (5/4/2005 and 12/4/2020). Baseline and clinical variables at the primary and re-DLTx were compared utilizing the paired student t-test. Graft survival was defined as time from surgery to retransplant and analyzed using Kaplan-Meier estimates. 277 CF patients who underwent re-DLTx experienced a significantly worse 5-year survival when compared to the primary DLTx cohort (47.9% vs 58.8%, p = 0.00012). The following differences were observed comparing CF re-DLTx group to their primary DLTx: higher LAS score at the time of listing (50.66 vs 42.15, p < 0.001) and transplant (62.19 vs 48.20, p < 0.001), and increase LAS from the time of listing to transplant (+12.22 vs +7.23, p = 0.002). While serum albumin and total bilirubin were similar, CF patients had a higher creatinine (1.05 vs 0.74, p < 0.001), dialysis (4.4% vs 0.6%, p < 0.001), ECMO bridge to transplant rates (7.6% vs 4.0%, p < 0.001), and higher oxygen requirements (5.95 vs 3.93, p < 0.001) at the time of listing for a re-DLTx. Compared to their initial transplant, CF patients experience significant clinical decline in renal, cardiac, and pulmonary function at the time of lung retransplantation. This may indicate that an earlier evaluation and rehabilitation process may be necessary to identify patients earlier for lung retransplantation prior significant clinical decline.


Idiopathic encapsulating peritonitis: report of two cases.
This report presents two cases of young males who developed the rare idiopathic form of sclerosing encapsulating peritonitis (SEP) presented as partial bowel obstruction, both diagnosed during surgical treatment, with satisfactory outcomes. Sclerosing encapsulating peritonitis is a rare and enigmatic condition, characterized by intraperitoneal fibrosclerosis, which causes intestinal obstruction. It is a chronic entity with a poorly elucidated pathophysiology, leading to the constitution of a thick white nacreous fibrosis membrane that wraps the bowel in a concertina-like fashion with some adhesions configuring an intra-abdominal cocoon. Sclerosing encapsulating peritonitis is reported in a wide variety of patients, including those who have undergone peritoneal dialysis, young adolescent girls, cirrhotic patients after peritoneal-venous shunting, and patients treated with β-blockers. Nevertheless, the etiology of SEP remains obscure. This entity presents many difficulties in preoperative diagnosis because of its peculiar characteristics. Recognition of the SEP results in proper management and prevents unnecessary bowel resection. Regardless of cause, the treatment of the obstruction is surgical, with dissection of the encasing membrane from the intestine and separation of adherent loops of small bowel until they are laid free and returned to their normal configuration. The prognosis after appropriate surgical therapy is good, but depends on coexisting diseases.


Assessment of intimate partner violence abuse ratings by recently abused and never abused women.
There are a paucity of directly reported intimate partner violence survivors' experiences, especially in women of color. This study measures recently/currently abused women's ratings of varied abuse events compared to ratings from never abused women. Women in a single, urban, public hospital emergency department (ED) were screened for intimate partner violence using the Abuse Assessment Screen (AAS). Two groups were identified - women abused within 1 year by an intimate partner or family member and those who screened negative for abuse. Using a two-group longitudinal survey and interview format, women completed visual analog scale ratings (0-100) for each of 20 abuse events/types. For analysis, each abuse type was placed on the 0-100 scale according to its designated rating. Average age of participants in the abuse group (n = 30) was 33. Never abused women averaged age 50 (n = 32). The majority of participants were African-American: abused 67% and never abused 94%. Abused women rated name-calling (p < 0.02) and put-downs (p < 0.01) as more severe than never abused women. Other non-physical and physical forms of abuse such as threats, control, burns or forced sex were perceived more similarly between groups. Abused women perceive verbal abuse events differently compared to never abused women.


Retention of configuration in the action of human plasma 3'-exonuclease on oligo(deoxynucleoside phosphorothioate). A new method for assignment of absolute configuration at phosphorus in isotopomeric deoxyadenosine 5'-O-[(18)O]phosphorothioate.
A new method of analysis has allowed the exonucleolytic cleavage by human 3'-exonuclease to be determined. Hydrolysis by human plasma 3'-exonuclease proceeds with retention of configuration at phosphorus. The new method determines the sense of chirality at phosphorus in isotopomeric adenosine 5'-O-[(18)O]phosphorothioates. This is based on stereospecific two-step conversion of the mono-thionucleotide into the corresponding deoxyadenosine 5'-O-alpha-[(18)O]thiotriphosphate, followed by the use of terminal deoxyribonucleotidyl transferase and MALDI TOF mass spectrometry of the resulting elongated primer. Retention of configuration in the reaction of plasma 3'-exonuclease implies a two-step mechanism with two displacements on phosphorus. Inversion at each step leads to overall retention.


Micropuncture comparison of nephron function during acute and chronic ADH excess in the rat.
1. The aim of this study was to compare the effect of acute versus chronic ADH administration on the handling of sodium, potassium and water by the nephron. Simultaneous clearance and free-flow micropuncture experiments were performed on rats, infused with hypotonic Ringer solution, following either 1-3 h ('acute') or 10-12 days ('chronic') of continuous treatment with arginine vasopressin, 50 mU/h. A third group of animals receiving no exogenous ADH acted as controls. 2. Chronic ADH treatment led to more profound concentration of the urine and antidiuresis than acute treatment, due to enhanced extraction of water in the renal medulla. 3. Fractional sodium excretion during this protocol was increased after 'acute' but not 'chronic' ADH treatment. The acute natriuretic response was brought about principally along the length of the proximal tubule, probably due to volume expansion and increased arterial blood pressure. 4. Fractional excretion of potassium was also increased by 'acute' ADH, but this response was due to stimulation of potassium secretion in the late distal tubule. 5. It is concluded that acute and chronic exposure to ADH have different effects on nephron function, as a result of both direct and indirect actions.


Association of Antibody Responses to Fusobacterium nucleatum and Streptococcus gallolyticus Proteins with Colorectal Adenoma and Colorectal Cancer.
Streptococcus gallolyticus subspecies gallolyticus (SGG) and Fusobacterium (F.) nucleatum have been implicated in colorectal carcinogenesis. Here, the association of immune responses to bacterial exposure with advancing stages of colorectal neoplasia was assessed by multiplex serology. Immunoglobulin (Ig) A and G antibody responses to eleven proteins each of F. nucleatum and SGG were measured in plasma of controls (n = 100) and patients with colorectal cancer (CRC, n = 25), advanced adenoma (n = 82), or small polyps (n = 85). Multivariable logistic regression was used to evaluate the association of bacterial sero-positivity with colorectal neoplasia. In a cohort subset with matched data (n = 45), F. nucleatum sero-positivity was correlated with bacterial abundance in both neoplastic and matched normal tissue. IgG sero-positivity to Fn1426 of F. nucleatum was associated with an increased CRC risk (OR = 4.84; 95% CI 1.46-16.0), while IgA sero-positivity to any SGG protein or specifically Gallo0272 and Gallo1675 alone was associated with increased advanced adenoma occurrence (OR = 2.02, 95% CI 1.10-3.71; OR = 2.67, 95% CI 1.10-6.46; and OR = 6.17, 95% CI 1.61-23.5, respectively). Only F. nucleatum abundance in the normal mucosa positively correlated with the IgA response to the Fn1426 antigen (Correlation coefficient (r) = 0.38, p < 0.01). Antibody responses to SGG and F. nucleatum were associated with occurrence of colorectal adenomas and CRC, respectively. Further studies are needed to clarify the role these microbes or the immune response to their antigens may have in colorectal carcinogenesis stages.


Identification of the novel HLA-A*240215 allele by haplotype-specific sequencing.
Here, we report on a novel allele human leukocyte antigen (HLA)-A*240215. This allele differs from HLA-A*240201 by a synonymous nucleotide exchange at nucleotide 255 in exon 2.


Anoxic granular activated sludge process for simultaneous removal of hazardous perchlorate and nitrate.
An airtight, anoxic bubble-column sequencing batch reactor (SBR) was developed for the rapid cultivation of perchlorate (ClO4-) and nitrate (NO3-) reducing granular sludge (GS) in this study. Feast/famine conditions and shear force selection pressures in tandem with a short settling time (2-min) as a hydraulic section pressure resulted in the accelerated formation of anoxic granular activated sludge (AxGS). ClO4- and NO3- were efficiently (>99.9%) reduced over long-term (>500-d) steady-state operation. Specific NO3- reduction, ClO4- reduction, chloride production, and non-purgeable dissolved organic carbon (DOC) oxidation rates of 5.77 ± 0.54 mg NO3--N/g VSS·h, 8.13 ± 0.74 mg ClO4-/g VSS·h, 2.40 ± 0.40 mg Cl-/g VSS·h, and 16.0 ± 0.06 mg DOC/g VSS·h were recorded within the reactor under steady-state conditions, respectively. The AxGS biomass cultivated in this study exhibited faster specific ClO4- reduction, NO3- reduction, and DOC oxidation rates than flocculated biomass cultivated under similar conditions and AxGS biomass operated in an up-flow anaerobic sludge blank (UASB) bioreactor receiving the same influent loading. EPS peptide identification revealed a suite of extracellular catabolic enzymes. Dechloromonas species were present in high abundance throughout the entirety of this study. This is one of the initial studies on anoxic granulation to simultaneously treat hazardous chemicals and adds to the science of the granular activated sludge process.


AM fungi facilitate the competitive growth of two invasive plant species, Ambrosia artemisiifolia and Bidens pilosa.
Invasive species often cause enormous economic and ecological damage, and this is especially true for invasive plants in the Asteraceae family. Arbuscular mycorrhizal fungi (AMF) play an important role in the successful invasion by exotic plant species because of their ability to promote growth and influence interspecific competition. However, few studies have evaluated the effects of invasive Asteraceae species on AMF diversity and how feedback mechanisms during competition with native species subsequently affect the accumulation of nutrient resources. Two exotic Asteraceae, Ambrosia artemisiifolia and Bidens pilosa, were monitored during competition with a native grass species, Setaria viridis, which is being replaced by these exotic species in natural areas around the study site. From these species continuously maintained in a field plot for 5 years, we collected the rhizosphere soil and cloned and identified soil AMF. Furthermore, AM fungal spores were isolated from rhizosphere soil of the two invasive species and used as inoculum in greenhouse experiments, to compare growth and nutrient accumulation during competition. The results indicate that although the AMF diversity in the rhizosphere soil of A. artemisiifolia and B. pilosa differed, the three most abundant species (Septoglomus viscosum, Septoglomus constrictum, Glomus perpusillum) were identical. The addition of AMF inoculum changed the competition between the plants, increasing the competitive ability of the invasives and decreasing that of the native. The results show a similar AMF community composition between A. artemisiifolia and B. pilosa, increased AMF root colonization of the invasive species during competition, AMF-enhanced N accumulation, and AMF-facilitated competitive growth of the invasive species.


Insights into dryland biocrust microbiome: geography, soil depth and crust type affect biocrust microbial communities and networks in Mojave Desert, USA.
Biocrusts are the living skin of drylands, comprising diverse microbial communities that are essential to desert ecosystems. Despite there being extensive knowledge on biocrust ecosystem functions and lichen and moss biodiversity, little is known about factors structuring diversity among their microbial communities. We used amplicon-based metabarcode sequencing to survey microbial communities from biocrust surface and subsurface soils at four sites located within the Mojave Desert. Five biocrust types were examined: Light-algal/Cyanobacteria, Cyanolichen, Green-algal lichen, Smooth-moss and Rough-moss crust types. Microbial diversity in biocrusts was structured by several characteristics: (i) central versus southern Mojave sites displayed different community signatures, (ii) indicator taxa of plant-associated fungi (plant pathogens and wood saprotrophs) were identified at each site, (iii) surface and subsurface microbial communities were distinct and (iv) crust types had distinct indicator taxa. Network analysis ranked bacteria-bacteria interactions as the most connected of all within-domain and cross-domain interaction networks in biocrust surface samples. Actinobacteria, Proteobacteria, Cyanobacteria and Ascomycota functioned as hubs among all phyla. The bacteria Pseudonocardia sp. (Pseudonocardiales, Actinobacteria) and fungus Alternaria sp. (Pleosporales, Ascomycota) were the most connected had the highest node degree. Our findings provide crucial insights for dryland microbial community ecology, conservation and sustainable management.


Evasion of cytotoxic T lymphocytes is a functional constraint maintaining HIV-1 Nef expression.
Nef expression is not required for HIV-1 replication and is highly targeted by CD8+ CTL, raising the question of why Nef expression is not lost in order to evade immunity in vivo. We explore whether MHC class I (MHC-I) down-regulation to evade CTL in general is a selective pressure maintaining Nef. HIV-1 with functional Nef (wild type, WT) is compared to virus containing a Nef point mutation (M20A) that selectively ablates MHC-I down-regulation. WT-infected cells are relatively resistant to cytolysis and less suppressed for viral replication by Gag- and RT-specific CTL compared to M20A. These viruses grow similarly in vitro in the absence of CTL, but the presence of Gag- or RT-specific CTL strongly favors WT overgrowth of M20A. Finally, while in vitro selection by Nef-specific CTL readily drives disruption of the nef reading frame, the addition of Gag- or RT-specific CTL markedly limits such escape. These data indicate that MHC-I down-regulation is an important function favoring Nef maintenance due to a net selective advantage in the setting of the general CTL response.


A Successful Implementation Strategy to Support Adoption of Decision Making in Mental Health Services.
Individual involvement in treatment decisions with providers, often through the use of decision support aids, improves quality of care. This study investigates an implementation strategy to bring decision support to community mental health centers (CMHC). Fifty-two CMHCs implemented a decision support toolkit supported by a 12-month learning collaborative using the Breakthrough Series model. Participation in learning collaborative activities was high, indicating feasibility of the implementation model. Progress by staff in meeting process aims around utilization of components of the toolkit improved significantly over time (p < .0001). Survey responses by individuals in service corroborate successful implementation. Community-based providers were able to successfully implement decision support in mental health services as evidenced by improved process outcomes and sustained practices over 1 year through the structure of the learning collaborative model.


Redefining KSHV latency.
In this issue of Cell Host & Microbe, Chang and Ganem (2013) report that Kaposi's sarcoma-associated herpesvirus infection of lymphatic endothelial cells (LECs), but not blood endothelial cells (BECs), activates mTORC1 signaling and sensitizes LECs to rapamycin-induced killing. The differential rapamycin sensitivity is explained by a unique LEC-specific virus latency program.


Adaptation to thermally variable environments: capacity for acclimation of thermal limit and heat shock response in the shrimp Palaemonetes varians.
In the context of climate change, there is a sustained interest in understanding better the functional mechanisms by which marine ectotherms maintain their physiological scope and define their ability to cope with thermal changes in their environment. Here, we present evidence that the variable shrimp Palaemonetes varians shows genuine acclimation capacities of both the thermal limit (CT(max)) and the heat shock response (hsp70 induction temperature). During cold acclimation to 10 °C, the time lag to adjust the stress gene expression to the current environmental temperature proved to exceed 1 week, thereby highlighting the importance of long-term experiments in evaluating the species' acclimation capacities. Cold and warm-acclimated specimens of P. varians can mobilise the heat shock response (HSR) at temperatures above those experienced in nature, which suggests that the species is potentially capable of expanding its upper thermal range. The shrimp also survived acute heat shock well above its thermal limit without subsequent induction of the HSR, which is discussed with regard to thermal adaptations required for life in highly variable environments.


Observations on the Anton antigen and antibody.
Five antisera with Anton specificity were studied serologically. The determinant is not sensitive to treatment by proteolytic enzymes (notably trypsin) and is present on cells of the recessive type of Lu(a-b-) phenotype. The Anton 'para-Lutheran' antigen/antibody therefore seems to be associated with the Lutheran blood group system only by means of cells of the dominant type of the Lu(a-b-) phenotype which is controlled by In(Lu), a gene independent of the Lutheran locus.


Healthy aging and chronic kidney disease.
The world population is aging and the prevalence of noncommunicable diseases such as diabetes, hypertension, and chronic kidney disease (CKD) will increase significantly. With advances in medical treatment and public health, the human lifespan continues to outpace the health span in such a way that the last decade of life is generally spent in poor health. In 2015, the World Health Organization defined healthy aging as 'the process of developing and maintaining the functional ability that enables wellbeing in older age.' CKD is increasingly being recognized as a model of accelerated aging and is associated with physical performance decline, cognitive decline, falls and fractures, poor quality of life, loss of appetite, and inflammation. Frailty and dementia are the final pathways and key determinants of disability and mortality independent of underlying disease. CKD, dementia, and frailty share a triangular relationship with synergistic actions and have common risk factors wherein CKD accelerates frailty and dementia through mechanisms such as uremic toxicity, metabolic acidosis and derangements, anorexia and malnutrition, dialysis-related hemodynamic instability, and sleep disturbance. Frailty accelerates glomerular filtration decline as well as dialysis induction in CKD and more than doubles the mortality risk. Anorexia is one of the major causes of protein-energy malnutrition, which is also prevalent in the aging population and warrants screening. Healthcare systems across the world need to have a system in place for the prevention of CKD amongst high-risk older adults, focusing on screening for poor prognostic factors amongst patients with CKD such as frailty, poor appetite, and cognitive impairment and providing necessary person-centered interventions to reverse underlying factors that may contribute to poor outcomes.


Hypercalcemic hyperparathyroidism and hypophosphatemic osteomalacia complicating neurofibromatosis.
Neurofibromatosis is sometimes complicated by impaired renal tubular reabsorption of phosphate, hypophosphatemia, and osteomalacia. Hyperparathyroidism has also been reported in patients with neurofibromatosis. When hypercalcemia and elevated levels of parathyroid hormone are found in osteomalacia, however, it may be difficult to determine if the hyperparathyroidism was primary or tertiary. We describe a patient with neurofibromatosis, hypercalcemic hyperparathyroidism, hypophosphatemic osteomalacia, vitamin D deficiency, and clear-cell hyperplasia of all four parathyroid glands. Serial biomechanical, bone biopsy, and densitometric studies confirmed that treatment with ergocalciferol, calcium, and phosphate supplements significantly improved the osteomalacia but caused increased parathyroid overactivity. After subtotal parathyroidectomy, the parathyroid hormone concentration became normal and the bone mineral content increased at the spine and hip, but inappropriate phosphaturia persisted. The findings indicate that hyperparathyroidism, osteomalacia, and vitamin D deficiency adversely affect each other.


Thalamic hyperdensity--is it a diagnostic marker for Sandhoff disease?
Sandhoff disease, also known as GM2-gangliosidoses variant 0, is caused by the deficient activity of both hexosaminidase A and hexosaminidase B. We report a 15-month-old boy diagnosed with Sandhoff disease by demonstrating the enzyme deficiency. The interesting finding was bilateral thalamic hyperdensity on the CT scan. The hyperdensity in all previously published cases was homogeneous and symmetric and limited to the thalamus; the cause still remains unknown. We suggest that the finding of dense thalami may be useful as a specific diagnostic criterion for the GM2-gangliosidoses and especially for Sandhoff disease.


End of life, death and dying in neonatal intensive care units in Latin America.
Most analyses of end of life decisions in Neonatal Intensive Care Units (NICUs) have come from Europe/English-speaking countries. Would decisions be different in Latin American NICUs? Therefore, we aim to evaluate the approach to dying infants/families in NICUs in Latin America. Multinational descriptive study of all deaths in babies born at >22 weeks in eight NICUs in five Latin American countries. Deaths were categorized as: (i) no Cardiopulmonary Resuscitation (CPR) or life support offered; (ii) life support initiated but do not resuscitate (DNR) orders written or no CPR provided; (iii) full life support and CPR; and (iv) unclassifiable. There were 100 deaths, 81% in >27 weeks. Seventeen infants received no CPR/life support at birth, 10 died in DR and seven in NICU. There were 27 infants in group 2, 54 in group three and two in group 4. No baby had care withdrawn or care withdrawn/CPR withheld. Thirty-two infants had 'do not resuscitate' order. Decisions without parents' involvement in 15%, both parents present at death 24% and sedatives/narcotics documented 14%. Latin American NICUs differ from those in Northern Europe/English-speaking countries. More deaths are accompanied by full life support and CPR. DNR orders are rare. Withdrawal of life support is virtually non-existent. Latin American's doctors are more likely to make decisions without the objections of family about withholding life-sustaining treatment.


Influence of microemulsion chirality on chromatographic figures of merit in EKC: results with novel three-chiral-component microemulsions and comparison with one- and two-chiral-component microemulsions.
Novel microemulsion formulations containing all chiral components are described for the enantioseparation of six pairs of pharmaceutical enantiomers (atenolol, ephedrine, metoprolol, N-methyl ephedrine, pseudoephedrine, and synephrine). The chiral surfactant dodecoxycarbonylvaline (DDCV, R- and S-), the chiral cosurfactant S-2-hexanol, and the chiral oil diethyl tartrate (R- and S-) were combined to create four different chiral microemulsions, three of which were stable. Results obtained for enantioselectivity, efficiency, and resolution were compared for the triple-chirality systems and the single-chirality system that contained chiral surfactant only. Improvements in enantioselectivity and resolution were achieved by simultaneously incorporating three chiral components into the aggregate. The one-chiral-component microemulsion provided better efficiencies. Enantioselective synergies were identified for the three-chiral-component nanodroplets using a thermodynamic model. Additionally, two types of dual-chirality systems, chiral surfactant/chiral cosurfactant and chiral surfactant/chiral oil, were examined in terms of chromatographic figures of merit, with the former providing much better resolution. The two varieties of two-chiral-component microemulsions gave similar values for enantioselectivity and efficiency. Lastly, the microemulsion formulations were divided into categories based on the number of chiral microemulsion reagents and the average results for each pair of enantiomers were analyzed for trends. In general, enantioselectivity and resolution were enhanced while efficiency was decreased as more chiral components were used to create the pseudostationary phase (PSP).


Comparative efficacy of respiratory personal protective equipment against viral respiratory infectious diseases in healthcare workers: a network meta-analysis.
With the epidemic of coronavirus disease 2019 (COVID-19), the healthcare workers (HCWs) require proper respiratory personal protective equipment (rPPE) against viral respiratory infectious diseases (VRIDs). It is necessary to evaluate which type of mask and manner of wearing is the best suitable rPPE for preventing the VRID. A Bayesian network meta-analysis was performed to comprehensively analyze the protective efficacy of various rPPE. This network meta-analysis protocol was registered in an international prospective register of systematic reviews (CRD42020179489). Electronic databases were searched for cluster randomized control trials (RCTs) of comparing the effectiveness of rPPE and wearing manner in preventing HCWs from VRID. The primary outcome was the incidence of laboratory-confirmed viral respiratory infection reported as an odds ratio (OR) with the associated 95% credibility interval (CrI). The secondary outcome was the incidence of clinical respiratory illness (CRI) reported as an OR with the associated 95% CrI. Surface under the cumulative ranking curve analysis (SUCRA) provided a ranking of each rPPE according to the primary outcome and the secondary outcome as data supplement. Six studies encompassing 12,265 HCWs were included. In terms of the incidence of laboratory-confirmed viral respiratory infection, the continuous wearing of N95 respirators (network OR, 0.48; 95% CrI: 0.27 to 0.86; SUCRA score, 85.4) showed more effective than the control group. However, in terms of reducing the incidence of CRI, there was no rPPE showing superior protective effectiveness. There are significant differences in preventive efficacy among current rPPE. Our result suggests that continuous wearing of N95 respirators on the whole shift can serve as the best preventive rPPE for HCWs from the VRID.


Added value of electromyography in the diagnosis of myopathy: A consensus exercise.
Currently, neurologists may primarily rely on blood biomarkers, muscle biopsy, MRI, and genetics in the diagnostic work-up of suspected myopathy. Using expert consensus as diagnostic reference standard, this study addressed the added value of electrodiagnostic medicine (EDX) in diagnosis of myopathies. One hundred ninety-four EDX evaluations of patients with a peer-review consensus diagnosis of myopathy were collected by seven European centres. Each patient was given three different consensus diagnoses: (1) the EDX diagnosis solely based on EDX results, (2) the pure clinical diagnosis based on all available information except EDX results, and (3) the final diagnosis including EDX and all additional information. The myopathies were grouped as muscular dystrophy (45), inflammatory myopathy (46), other aetiology (36) or unknown aetiology (67). Higher diagnostic probabilities for myopathy were seen in the final diagnosis compared to the pure clinical diagnosis (p<0.001). Adding EDX information increased the diagnostic probability of myopathy in 67 patients (34.4%). The greatest increase was seen for myopathies of unknown aetiology. EDX has a major impact in the diagnosis of myopathies of unknown aetiology. In genetically or biopsy proven myopathies, EDX generally supports the diagnosis. EDX is still a useful tool in the diagnostic work-up of most patients with suspected myopathy.


The fine structure of Strongylocentrotus purpuratus testes.
The fine structure os Strongylocentrotus purpuratis testes has been examined. No obviously important differences appear to exist between the description reported here and the published fine structure of testes obtained from other sources. The most useful fixative was found to be a mixture of glutaraldehyde-paraformaldehyde.


Differential decreases in c-fos and aldolase C mRNA expression in the rat cerebellum after repeated administration of methamphetamine.
The effects of repeated methamphetamine administration on c-fos mRNA and aldolase C (Zebrin) mRNA expression in the rat cerebellum were investigated. A single dose of methamphetamine induced c-fos mRNA expression in granule and Purkinje cells of both anterior and posterior lobes. In the posterior lobe, in particular, c-fos mRNA signals were distributed in a parasagittal organization, like Zebrin bands. Repeated methamphetamine injections reduced methamphetamine-induced c-fos mRNA signals in the anterior hemisphere and in part of the posterior vermis (lobule VII) and posterior hemisphere. Aldolase C mRNA signals in Purkinje cells decreased only in lobules where methamphetamine-induced c-fos signals were not reduced (lobules VI and IX). Therefore, differential decreases in c-fos mRNA and aldolase C mRNA expression after repeated methamphetamine administration depend upon the localization of Purkinje cells in the cerebellum. Since c-fos mRNA and aldolase C mRNA expressions are markers of excitability and the metabolic state of Purkinje cells, respectively, hypofunction of inhibitory Purkinje cells could be induced if methamphetamine is repeatedly injected. Since repeated methamphetamine administration in this experimental paradigm increased horizontal movement and the rearing activity of rats, the hemisphere of the cerebellum may be involved in development of methamphetamine-induced motor behavioral sensitization in addition to the striatum and the nucleus accumbens.


Coenzyme precursor-assisted cooperative overexpression of an active pyridoxine 4-oxidase from Microbacterium luteolum.
The overexpression system of the active pyridoxine 4-oxidase from Microbacterium luteolum was developed. When chaperonin GroEL/ES genes in plasmid pKY206 were coexpressed, the pyridoxine 4-oxidase gene cloned in the vector pTrc99A was overexpressed in Escherichia coli JM109 cultured in LB medium containing 50microM riboflavin, the precursor of coenzyme (FAD) of the enzyme, under the cold stress at 23 degrees C. The crude extract from the cotransformant cells showed 88-fold higher specific activity than that from M. luteolum. The chaperonins, cold stress, and the riboflavin cooperatively served to increase the soluble form of the enzyme. A significant correlation between the specific activity and percentage of the soluble form in the total expressed enzyme was found. The overexpressed pyridoxine 4-oxidase was easily purified to homogeneity with two steps of the conventional column chromatography.


Deep dermal fibroblasts contribute to hypertrophic scarring.
Hypertrophic scar (HTS) following thermal injury is a dermal fibroproliferative disorder that leads to considerable morbidity. The development of HTS involves numerous cell types and cytokines with dermal fibroblasts being a key cell. We have previously reported that the phenotype of fibroblasts isolated from HTS was altered compared to fibroblasts from normal skin. In this study, normal skin was horizontally sectioned into five layers using a dermatome from which fibroblasts were isolated and cultured. Cells from the deeper layers were observed to proliferate at a slow rate, but were morphologically larger. In ELISA and FACS assays, cells from the deeper layers produced more TGF-beta1 and TGF-beta1 producing cells were higher. In quantitative RT-PCR, the cells from the deeper layers had higher CTGF and HSP47 mRNA levels compared to those from superficial layers. In western blot, FACS and collagen gel assays, fibroblasts from the deeper layers produced more alpha-smooth muscle actin (alpha-SMA), had higher alpha-SMA positive cells and contracted collagen gels more. Fibroblasts from the deeper layers were also found to produce more collagen, but less collagenase by mass spectrometry and collagenase assay. Interestingly, cells from the deeper layers also produced more of the proteoglycan, versican, but less decorin. Taken together, these data strongly demonstrate that fibroblasts from the deeper layers of the dermis resemble HTS fibroblasts, suggesting that the deeper layer fibroblasts may be critical in the formation of HTS.


Comparison of live Eimeria vaccination with in-feed salinomycin on growth and immune status in broiler chickens.
Coccidiosis vaccines and anticoccidial drugs are commonly used to control Eimeria infection during commercial poultry production. The present study was conducted to compare the relative effectiveness of these two disease control strategies in broiler chickens in an experimental research facility. Birds were orally vaccinated with a live, attenuated vaccine (Inovocox), or were provided with in-feed salinomycin (Bio-Cox), and body weights, serum levels of nitric oxide (NO) and antibodies against Eimeria profilin and Clostridium perfringens PFO proteins, and intestinal levels of cytokine gene transcripts were measured. Vaccinated chickens had increased body weights, greater NO levels, and higher profilin and PFO antibody levels compared with salinomycin-fed birds. Transcripts for interleukin-6 (IL-6), tumor necrosis factor superfamily 15, and interferon-γ were increased, while mRNAs for IL-4 and IL-10 were decreased, in immunized chickens compared with salinomycin-treated chickens. In conclusion, vaccination against avian coccidiosis may be more effective compared with dietary salinomycin for increasing body weight and augmenting pro-inflammatory immune status during commercial poultry production.


Multi-class classification algorithm for optical diagnosis of oral cancer.
We report development of a direct multi-class spectroscopic diagnostic algorithm for discrimination of high-grade cancerous tissue sites from low-grade as well as precancerous and normal squamous tissue sites of human oral cavity. The algorithm was developed making use of the recently formulated theory of total principal component regression (TPCR). The in vivo autofluorescence spectral data acquired from patients screened for neoplasm of oral cavity at the Government Cancer Hospital, Indore, was used to train and validate the algorithm. The diagnostic algorithm based on TPCR was found to provide satisfactory performance in classifying the tissue sites in four different classes - high-grade squamous cell carcinoma, low-grade squamous cell carcinoma, leukoplakia, and normal squamous tissue. The classification accuracy for these four classes was observed to be approximately 94%, 100%, 100% and 91% for the training data set (based on leave-one-out cross-validation), and was approximately 90%, 90%, 85% and 88%, respectively for the corresponding classes for the independent validation data set.


Osteoprotegerin is associated with depletion of circulating endothelial progenitor cells and elevation in pulmonary arterial pressure in patients with systolic heart failure.
Osteoprotegerin (OPG) may predict progression of chronic congestive heart failure (CHF) with increased mortality and play an important role in the development of pulmonary arterial hypertension (PAH). Mounting evidence suggests that PAH developed during CHF is not solely caused by a "passive" increase from the left ventricular enddiastolic pressure, but rather a "reactive" response from contributing lung endothelial dysfunction and vascular remodelling, a pathological process that can be significantly influenced by endothelial progenitor cells (EPCs).This study aims to examine whether circulating EPCs from patients with CHF are affected and if OPG could be implicated during disease progression. In this study EPCs were isolated, cultured, and quantified from patients of CHF with (n = 20) or without PAH (n=40) as measured by right heart catheterization. Serum levels of OPG and N-terminal pro-brain natriuretic peptide (NT-pro BNP) were analysed and correlated with EPCs. A significant decrease in circulating EPCs (39.3 ?9.1 vs 67.1 ?10.5 EPCs/x200 field; P <0.05) was found in CHF patients who developed PAH compared to those without PAH. Both OPG (551.90 +/- 49.83 vs. 312.29 +/- 31.12 pg/ml; P<0.05) and NT-pro BNP (2,946.50 +/- 1,434.50 vs. 1,328.20 +/- 811.90; P < 0.05) were also significantly elevated in CHF patients with PA H. Circulating level of OPG correlated inversely with EPCs (r = -0.45, P = 0.037) but positively with mPAP (r =0.53, P=0.011). Our study demonstrates that OPG elevation and EPC depletion are associated with CHF patients who have developed PAH. The inverse relationship of circulating OPG with EPCs suggests a possible mechanism for OPG in the development of pulmonary vascular dysfunction, thus worsening prognosis for CHF patients.


Evidence for efferent effects on early components of the human auditory brain-stem evoked potentials.
Auditory brain-stem evoked potentials (ABEPs) were recorded from 10 normal hearing subjects in response to rarefaction clicks, presented at a rate of 11/s. Stimuli were binaurally symmetrical and isochronic at 75 dB peSPL or with interaural time disparities (ITDs) of +/-0.4 ms, or intensity disparities (IIDs) of +/-10 dB. Potentials were recorded from vertex-neck, as well as from 3 orthonormally positioned differential derivations. The amplified potentials were averaged over 8000 repetitions using a dwell time of 20 micros/address/channel. The effects of contralateral stimulation on neural responses of the peripheral auditory system were obtained by subtracting the binaural response from the algebraic sum of responses to left and right monaural stimuli. From the 3 orthonormal derivations, 3-channel Lissajous' trajectories (3-CLTs) to the various stimulus conditions and difference waveforms were derived. The results corroborated earlier studies on binaural interaction components (BICs), which include 3 major components corresponding in latency to the vertex-mastoid peaks IV-VI of ABEP. In addition, the binaural difference waveforms included 3 earlier, low-amplitude components. Latency correspondence and comparison of difference waveform and ABEP 3-CLTs indicated that the first and third early difference waveform components corresponded to the negative peaks following I and III, respectively, of the vertex-neck ABEP to binaural clicks. These results indicate that early ABEP peaks, generated peripheral to binaural convergence, may be affected by contralateral stimulation. These contralateral effects were in a pattern compatible with suppression. most probably by efferents of the olivo-cochlear bundle.


Probing the effect of Ni, Co and Fe doping concentrations on the antibacterial behaviors of MgO nanoparticles.
The divalent transition metal ions (Ni, Co, and Fe)-doped MgO nanoparticles were synthesized via the sol-gel method. X-ray diffraction showed the MgO pure, single cubic phase of samples at 600 °C. Field emission electron microscope showed the uniform spherical shape of samples. The magnetic behavior of Ni, Co, Fe-doped MgO system were varied with Ni, Co, Fe content (0.00, 0.01, 0.03, 0.05, 0.07). The magnetic nature of pure had changed from paramagnetic to ferromagnetic. The number of oxygen vacancies increases with increasing amounts of dopant ions that lead to an ionic charge imbalance between Ni2+/Co2+/Fe2+ and Mg2+, leading to increase magnetic properties of the samples. The magnetic nature of prepared samples makes them suitable for biomedical applications. A comparative study of the antibacterial activity of nanoparticles against the Gram-negative (E. coli) and Gram-positive bacteria (S. aureus) was performed by disc diffusion, pour plate techniques, and study surface morphology of untreated and treated bacterial cell wall. An investigation of the antibacterial activity of doped MgO nanoparticles reveals that the doped MgO nanoparticles show effective antibacterial activity against the Gram-negative (E. coli) and Gram-positive (S. aureus) bacterium. The minimum inhibitory concentration of the synthesized nanoparticles against microorganisms was recorded with 40 μg/ml, while the maximum inhibitory concentration was observed with 80 μg/ml. At a concentration of 80 μg/ml, the complete growth inhibition of the E. coli was achieved with 7% Co-doped MgO and 7% Fe-doped MgO, while bacterial growth of S. aureus was inhibited by 100% in the presence of 7% Fe-doped MgO. The present work is promising for using nanomaterials as a novel antibiotic instead of the conventional antibiotics for the treatment of infectious diseases which are caused by tested bacteria.


Fine structure of the rabbit adrenal cortex and the effects of short-term ACTH administration.
The fine structure of the rabbit adrenal cortex was investigated. The parenchymal cells display the ultrastructural features of steroid-producing cells, and also contain numerous electron-dense bodies frequently located near intercellular canaliculi, when open into the subendothelial space. Short-term ACTH-administration induced a noticeable decrease in the volume of the lipid compartment in the cells of all three cortical zones and a significant increase in the volume of dense bodies in the cells of zona fasciculata and zona reticularis. The hypothesis that these dense bodies are secretory granules is discussed in the light of biochemical evidence showing that ACTH increases the concentration of both corticosterone and cortisol in the decapsulated-enucleated adrenal homogenate and does not affect the activity of two lysosome-marker enzymes (i.e., acid phosphatase and beta-glucuronidase).


The roles of school racial climate and science, technology, engineering, and mathematics classroom climate in adolescents' gender and racial peer inclusion and attribution decisions.
Adolescents use social identities and reasoning to make peer inclusion and attribution decisions. School climate plays a role in these decisions. Thus, this study analyzed how school racial climate and STEM (science, technology, engineering, and math) classroom climate were associated with the choices of adolescents (N = 294; Mage = 15.72 years; 52.3 % female; 36.7 % White/European American, 32.9 % Black/African American, 11.2 % Latino/Hispanic [the most common racial/ethnic groups in the schools where data collection took place]) in two tasks: peer inclusion and attribution of ability. On the peer inclusion task, participants were more likely to choose a non-White peer for a STEM activity if they had lower perceptions of stereotyping at school, and they were more likely to choose a female peer if they were female. Participants were more likely to use reasoning based on personal characteristics when choosing a peer, but female participants who chose a female peer were more likely to use reasoning based on gender. On the attribution task, participants were more likely to choose a non-White peer if they perceived greater STEM connectedness, and they were more likely to choose a White or male peer if they had more positive relationships with their STEM teachers. Therefore, students' perceptions of school racial climate relate to adolescents' peer inclusion decisions, and their perceptions of STEM classroom climate relate to adolescents' ability attributions. Schools may need to focus on creating welcoming school and classroom environments as a way to promote equity in STEM.


Hepatic sensitivity to imipramine.
A case of significant hepatic reaction related to imipramine is presented, documented by challenge with imipramine and liver biopsy. The mechanism, while not entirely clear, is presumed to involve hypersensitivity or induction of toxic metabolites.


Food Allergies in Inner-City Schools: Addressing Disparities and Improving Management.
Food allergy (FA) affects approximately 8% of children in the United States. Management comprises both preventing and treating allergic reactions, which poses unique challenges in the inner-city school setting. In this article, we review the epidemiology of FA in school-aged children and management challenges and opportunities specific to the inner-city population. A literature search of the PubMed database was performed to identify published literature on FA epidemiology, FA management, school policies, disparities, inner-city, race, ethnicity, and socioeconomic status. Relevant articles on FA management best practices and challenges in schools, with a particular emphasis on inner-city schools and populations and socioeconomic, racial, and ethnic disparities, were reviewed in detail. Disparities in FA prevalence, management, and treatment exist. Additional research is needed to better characterize these disparities and elucidate the mechanisms leading to them. There is a lack of evidence-based interventions for the prevention and treatment of food allergic reactions in schools and specifically in inner-city schools, in which a greater proportion of students may rely on school food. There are opportunities for partnership among health care providers, schools, and communities to address unmet needs in FA management and disparities in the inner-city school setting.


Developmental apraxia: diagnostic considerations.
This study compares the performance of developmentally apraxic children with that of children who have functional articulation disorders on a battery of diagnostic tests. Based on preliminary data, tests which assess auditory attention, auditory discrimination, auditory memory, oral-tactile feedback, and isolated and sequenced volitional oral movements appear to be useful in a differential diagnosis of articulatory defective children and, thus, warrant further study. Implications of these findings are discussed.


Metabolic effects of glucose compared with invertose and a mixture of fructose, glucose and xylitol before and after moderate surgical trauma.
The metabolic and clinical effects of different isocaloric carbohydrate infusions were studied perioperatively in 54 female patients undergoing cholecystectomy. The patients were randomized to six treatment groups, who received infusions only postoperatively (group 1, 2 and 3) or pre- as well as postoperatively (group 4, 5 and 6). One litre was given during 8 h as a 12% infusion solution. Glucose (group 1 and 4) was compared to invertose (group 2 and 5) and to a mixture of fructose, glucose and xylitol 2:1:1 i.e. Triofusin (group 3 and 6). The glycogen content in liver biopsies, taken peroperatively, was significantly higher when infusions were given preoperatively. No significant differences were found between groups, when comparing the different carbohydrate infusions. A minor glucose intolerance was noticed postoperatively, especially in group 4, whereas no fructose or xylitol intolerance was seen. Lactataemia was insignificant and acid-base balance normal in all groups. Serum urea concentrations were lower when preoperative infusions were given but without differences between groups 4, 5 and 6. Electrolytes, creatinine, hemoglobin, hematocrite and liver function tests were unaltered and the clinical course was uncomplicated in all cases. No side effects were observed. It is concluded that the infusion of one litre 12% Triofusin can be used as effectively and safely as 12% glucose and invertose before and after moderate surgical trauma. But no obvious advantage with Triofusin was revealed.


Long chain fatty acid binding to human plasma albumin.
The binding of six physiologically important long chain fatty acids to defatted human plasma albumin was measured at 37 degrees in a calcium-free Krebs-Ringer phosphate buffer, pH 7.4. The data were analyzed in terms of multiple stepwise equilibria. With the saturated acids, the magnitude of the equilibrium (association) constants, Ki, increased as the chain length increased: laurate smaller than myristate smaller than palmitate smaller than stearate. Oleate was bound more tightly than stearate; by contrast, linoleate was bound less tightly than stearate. The equilibrium constants, K1 through K12, ranged from 2.4 times 10-6 - 3.5 times 10-3 m-1 for laurate to 2.6 times 10-8 - 3.5 times 10-5 m-1 for oleate. Successive values of Ki decrease for each of the acids, indicating that major cooperative binding effects do not occur over the physiological range of fatty acid concentrations. In no case could the Ki be segregated into distinct classes, suggesting that any grouping of albumin binding sites is somewhat arbitrary. The results were inconclusive concerning whether premicellar association of unbound fatty acid occurs. Although corrections for premicellar association produced very little change in the Ki values for myristate, they raised the Ki for palmitate and stearate by 300 to 700 per cent. A sigmoidal relationship was obtained when the logarithm of Ki was plotted against chain length for the saturated fatty acids containing 6 to 18 carbon atoms, indicating that the binding energy is not simply a statistical process dependent only on the fatty acid chain length. This selectivity that albumin contributes to the binding process may be due to varying degrees of configurational adaptability of its binding sites as the fatty acid increases in length.


Effectiveness of terlipressin for prevention of complications after major liver resection - A randomized placebo-controlled trial.
Elevated portal pressure in response to major liver resection is associated with impaired liver regeneration and increased postoperative complications. Terlipressin, a splanchnic vasoconstrictor used for treatment of hepatorenal syndrome, was tested for reduction of complications and renal protection after liver resection. A randomized double-blinded placebo-controlled trial including patients undergoing elective major liver resection was performed. Terlipressin was administered to patients in the intervention group for five days. The primary outcome parameter was the incidence of a clinical composite endpoint of following liver specific complications 6 weeks after surgery: liver failure, ascites, bile leakage, intra-abdominal abscess and operative mortality. Postoperative kidney function was assessed as a secondary endpoint. 150 patients (mean age 63.4 years, 73.3% male) were included. No difference was found in the composite endpoint between the placebo and intervention group (32.8% versus 30.8%, relative risk 1.066, 95%CI 0.643 to 1.769, p = 0.85). Patients receiving terlipressin showed a significant lower decrease in postoperative estimated glomerular filtration rate compared to placebo (two way ANOVA, p = 0.005). Perioperative administration of terlipressin during major liver surgery did not affect a composite endpoint of liver specific complications, but significantly protected from postoperative deterioration of kidney function compared to placebo. CLINICALTRIALS. NCT01921985.


UMODL1/Olfactorin is an extracellular membrane-bound molecule with a restricted spatial expression in olfactory and vomeronasal neurons.
The olfactory system provides a unique model for developmental neurobiology. Precise targeting of axonal projections from sensory neurons located in the olfactory epithelium to specific neurons in the olfactory bulb establishes a highly refined spatial sensory map. Distinctively, this process is not restricted to embryonic stages, but continues during the entire life of mammals. A number of secreted and membrane molecules have been implicated in guidance and targeting of olfactory sensory neurons. Here we describe olfactorin, the protein product of the mouse Umodl1 gene, as a potential new element in this process. Olfactorin is a secreted modular protein containing several domains typically present in extracellular matrix proteins (EMI, WAP, FNIII, Ca2+ -binding EGF-like, SEA and ZP domains). By in situ hybridization we find that during embryonic development expression of the Umodl1 gene is detectable only in the olfactory epithelium and vomeronasal organ starting at embryonic day 16.5. At this stage, Umodl1 expression within the olfactory epithelium is punctate, and is restricted to only some of the sensory neurons. At birth and postnatally, expression in these organs continues and involves more neurons. Kallmann syndrome is a genetic disease in which olfactory axons fail to connect to target neurons in the bulb. We tested whether olfactorin might be responsible for an autosomal form of this disease and show that this is not the case. However, based on its domain composition and on the expression in olfactory neurons we suggest that olfactorin may play a role in correct olfactory axon navigation to the brain.


[The effect of antiviral therapy for patients with HBeAg-negative cirrhosis].
To investigate the efficacy of nucleot(s)ide analogues therapy in patients with HBeAg-negative cirrhosis in China. 111 patiens with HBeAg-negative cirrhosis were divided into antiviral group (58 cases, 25 entecavir, 19 adefovir dipivoxil, 13 lamivudine, 1 telbivudine) and control group (53 cases, supportive and symptomatic treatment). These two groups were matched for demography, liver function and Child-Pugh score. At the 96th week, the rate of ALT normalization and HBV DNA drop (1g copies/ml) in antiviral group were higher than those in control group (P < 0.05). The rates of HBV DNA negative (< 500 copies/ml) were 88.7% (47/53) and 32. 5% (13/40), respectively (P < 0.05 ). There were no differences in the rates of developing HCC and undergoing variceal bleeding between antiviral group and control group (P > 0.5). 15.4% patients with lamivudine treatment emerged YMDD mutations. 10.5% patients with adefovir dipivoxil treatment emerged virologic breakthrough and hepatitis flare during the second year. 2 patients (3.5%) in treatment group and 6 patients (11.5%) in control group died of liver failure or variceal bleeding or HCC ( P > 0.05 ). Neucleot(s)ide analogues are effective in suppressing HBV replication in patients with HBeAg-negative cirrhosis, but the impact of which on the mortality and complications of cirrhosis should be prolongly observed. For continuing treatment, the neucleot(s)ide analogues with strong effective and low resistance are the first choices to prevent viral mutation and drug resistance.


Applying sorting algorithms to sensory ranking tests - A proof of concept study.
In a sensory or consumer setting, panelists are commonly asked to rank a set of stimuli, either by the panelist's liking of the samples, or by the samples' perceived intensity of a particular sensory note. Ranking is seen as a "simple" task for panelists, and thus is usually performed with minimal (or no) specific instructions given to panelists. Despite its common usage, seemingly little is known about the specific cognitive task that panelists are performing when ranking samples. It becomes quickly unruly to suggest a series of paired comparisons between samples, with 45 individual paired comparisons needed to rank 10 samples. Comparing a number of elements with regards to a scaled value is common in computer science, with a number of differing sorting algorithms used to sort arrays of numerical elements. We compared the efficacy of the most basic sorting algorithm, Bubble Sort (based on comparing each element to its neighbor, moving the higher to the right, and repeating), vs a more advanced algorithm, Merge Sort (based on dividing the array into sub arrays, sorting these sub arrays, and then combining), in a sensory ranking task of 6 ascending concentrations of sucrose (n = 73 panelists). Results confirm that as seen in computer science, a Merge Sort procedure performs better than Bubble Sort in sensory ranking tasks, although the perceived difficulty of the approach suggests panelists would benefit from a longer period of training. Lastly, through a series of video recorded one-on-one interviews, and an additional sensory ranking test (n = 78), it seems that most panelists natively follow a similar procedure to Bubble Sorting when asked to rank without instructions, with correspondingly inferior results to those that may be obtained if a Merge Sorting procedure was applied. Results suggests that ranking may be improved if panelists were given a simple set of instructions on the Merge Sorting procedure.


Qualities of a French version of the Wolf Motor Function Test: a multicenter study.
There are currently a small number of standardized tools in French that measure and compare the effect of constraint-induced movement therapy, or other recent therapies promoting motor recovery To create a French version of the Wolf Motor Function Test (WMFT) and assess its reliability, minimal detectable change, and criterion validity. Prospective multicenter repeated-measure design with 44 patients with post stroke hemiparesis. A French Version of the WMFT was created; it was then assessed against the Fugl Meyer Assessment-Upper Extremity (French version) to establish its reliability, the minimal detectable change and its validity. Inter-rater reliability was very good. Reproducibility of the scores was good. Cronbach α coefficients showed adequate internal consistency. The minimal detectable change (MDC95%) for functional ability scores was below 10% of the highest possible score; the MDC95% for performance time was very high at more than 90 seconds. Criterion validity was good. The French version of the WMFT is reliable and valid. The test shows promise for use as an objective outcome measure for people post stroke in French speaking countries.


At the end of the 14C time scale--the Middle to Upper Paleolithic record of western Eurasia.
The dynamics of change underlying the demographic processes that led to the replacement of Neandertals by Anatomically Modern Humans (AMH) and the emergence of what are recognized as Upper Paleolithic technologies and behavior can only be understood with reference to the underlying chronological framework. This paper examines the European chronometric (mainly radiocarbon-based) record for the period between ca. 40 and 30 ka 14C BP and proposes a relatively rapid transition within some 2,500 years. This can be summarized in the following falsifiable hypotheses: (1) final Middle Paleolithic (FMP) "transitional" industries (Uluzzian, Chatelperronian, leaf-point industries) were made by Neandertals and date predominantly to between ca. 41 and 38 ka 14C BP, but not younger than 35/34 ka 14C BP; (2) initial (IUP) and early (EUP) Upper Paleolithic "transitional" industries (Bachokirian, Bohunician, Protoaurignacian, Kostenki 14) will date to between ca. 39/38 and 35 ka 14C BP and document the appearance of AMH in Europe; (3) the earliest Aurignacian (I) appears throughout Europe quasi simultaneously at ca. 35 ka 14C BP. The earliest appearance of figurative art is documented only for a later phase ca. 33.0/32.5-29.2 ka 14C BP. Taken together, the Middle to Upper Paleolithic transition appears to be a cumulative process involving the acquisition of different elements of "behavioral modernity" through several "stages of innovation."


Exercise-induced increase in hydrogen peroxide plasma levels is diminished by endurance training after myocardial infarction.
We have investigated the influence of physical training on exercise-induced changes in free radical activity in patients after myocardial infarction. Seventeen patients admitted to the cardiac rehabilitation center performed a bicycle ergometry before and after a 3-week endurance training program. The oxygen consumption and carbon dioxide production were measured and the ECG and the systemic blood pressure were monitored during the tests. Blood samples for acid-base equilibrium, lactic acid levels and hydrogen peroxide concentrations were collected directly before and after each exercise test. Exercise-induced increases in systolic blood pressure, heart rate and rate-pressure product as well as lactic acid concentrations were significantly less marked during the bicycle ergometry performed after the rehabilitation program. During the initial exercise test hydrogen peroxide levels increased significantly from 7.15+/-0.74 micromol/l before to 9.09+/-1.04 micromol/l 3 min after the test (P=0.0229). In contrast, no significant changes in hydrogen peroxide concentrations were observed during the exercise test performed after the training (6.31+/-1.05 micromol/l before the test, 5.85+/-1.08 micromol/l after the test, P=0.201). These observations suggest that physical training may have a beneficial influence on free radicals' generation in patients after myocardial infarction.


The pathophysiology of pityriasis alba: Time-dependent histologic changes.
Although pityriasis alba is a common dermatologic condition, its pathogenesis is poorly understood, and there are many discrepancies in the literature. To assess the effect of the duration of disease on the histologic findings, a search of cases labeled "pityriasis alba" was performed on any cases submitted to our dermatopathology laboratory. Of 179 cases of pityriasis alba, five cases identified the duration of the disease, when the biopsy was taken. A biopsy for a lesion of only 1-month duration demonstrated groups of large, prominent melanocytes heaped up upon one another. Compared with biopsies from patients who had the lesions for increasingly longer periods of time, it was apparent that the melanocytes became progressively less abundant and smaller with less prominent dendritic processes. The time that the biopsy is taken may affect the histologic findings of pityriasis alba. Additionally, an abundance of melanosomes was observed between the melanocytes in all sections examined which may reflect a problem with the transfer of melanosomes into keratinocytes in this condition.


The mouse Krüppel-like Factor 4 (Klf4) gene: four functional polyadenylation sites which are used in a cell-specific manner as revealed by testicular transcript analysis and multiple processed pseudogenes.
The transcription factor Krüppel-like factor 4 (Klf4) is involved in cell cycle arrest and terminal differentiation of many epithelial cell types. We have recently shown that Northern blot analysis of RNA from adult mouse testis revealed multiple Klf4 transcripts. In order to characterize these transcripts, we tested for alternative splicing events and looked for alternative transcriptional initiation and usage of different polyadenylation signals. We neither obtained evidence for alternative splicing nor found transcripts with novel 5' ends. However, we found striking differences in the 3' ends by RACE-PCR. These differences were, interestingly, due to the usage of four alternatively used polyadenylation signals (PAS). This high number of PAS is found in less than 1% of all genes. We show that testicular Sertoli cells exclusively use the first PAS, which is, notably, not canonical, while haploid germ cells rather use the more 3' located PAS-II-IV. The longer transcripts present in germ cells exhibit highly conserved putative binding motifs for proteins known to be important for translational regulation in germ cells. Moreover, we experimentally confirm an intron which was not described in a previous report on the Klf4 gene structure. Finally, we document six Klf4 pseudogenes most likely formed by L1-mediated retrotransposition, indicating germ line expression of Klf4. In summary, we show that mouse testicular cells make intensive use of alternative polyadenylation of Klf4 mRNA strongly suggesting translational regulation of the Klf4 message in spermatids.


Multi-objective Genetic Algorithm for De Novo Drug Design (MoGADdrug).
A multi-objective genetic algorithm for De novo drug design (MoGADdrug) has been proposed in this paper for the design of novel drug-like molecules similar to some reference molecules. The algorithm developed accepts a set of fragments extracted from approved drugs and available in fragment libraries and combines them according to specified rules to discover new drugs through the in-silico method. For this process, a genetic algorithm has been used, which encodes the fragments as genes of variable length chromosomes and applies various genetic operators throughout the generations. A weighted sum approach is used to simultaneously optimize the structural similarity of the new drug to a reference molecule as well as its drug-likeness property. Five reference molecules namely Lidocaine, Furano-pyrimidine derivative, Imatinib, Atorvastatin and Glipizide have been chosen for the performance evaluation of the algorithm. Also, the newly designed molecules were analyzed using ZINC, PubChem databases and docking investigations.


Plant PAXX has an XLF-like function and stimulates DNA end joining by the Ku-DNA ligase IV/XRCC4 complex.
Non-homologous end joining (NHEJ) plays a major role in repairing DNA double-strand breaks and is key to genome stability and editing. The minimal core NHEJ proteins, namely Ku70, Ku80, DNA ligase IV and XRCC4, are conserved, but other factors vary in different eukaryote groups. In plants, the only known NHEJ proteins are the core factors, while the molecular mechanism of plant NHEJ remains unclear. Here, we report a previously unidentified plant ortholog of PAXX, the crystal structure of which showed a similar fold to human 'PAXX'. However, plant PAXX has similar molecular functions to human XLF, by directly interacting with Ku70/80 and XRCC4. This suggests that plant PAXX combines the roles of mammalian PAXX and XLF and that these functions merged into a single protein during evolution. This is consistent with a redundant function of PAXX and XLF in mammals.


Genomic structure and subcellular localization of MAL, a human T-cell-specific proteolipid protein.
Genomic DNA clones containing the T-cell-specific human MAL gene were isolated. Restriction and sequence analysis revealed four exons and three introns. Each hydrophobic segment of MAL together with its adjacent hydrophilic sequence correlates closely with one exon of the gene. RNase protection analysis revealed that the previously described MAL mRNA, which contains the sequences present in the four exons, is the mRNA species predominant in T-cells. A remarkable similarity was found between the hydrophobicity pattern of MAL and those of the peripheral membrane protein 22 (PMP-22) and the 16-kDa proteolipid of vacuolar H(+)-ATPase. Direct evidence supporting that MAL is a proteolipid was obtained by extracting bacterial lysates expressing recombinant MAL protein with lipophilic solvents used to extract lipids. The use of two different antibodies raised against distinct peptides from the MAL molecule has allowed the localization of MAL in the endoplasmic reticulum of T-cells. This subcellular localization is in agreement with the presence of a RWKSS motif in the COOH-terminal tail of MAL, next to its last putative transmembrane domain, that fits with one of the consensus sequences (RXKXX) for residency in the endoplasmic reticulum for transmembrane proteins. A possible function for MAL protein in T-cells is discussed based on its subcellular localization and the unique lipid-like properties of the proteolipid proteins.


Submucosal tumors of the colon: experience with twenty-five cases.
Submucosal tumors of the colon are rare and require alertness on the part of the physician for early diagnosis. These tumors may not cause symptoms before attaining large size. In most cases the clinical histories are atypical. Because of the possibility of malignancy, adequate diagnosis and treatment are necessary. This report deals with 25 cases of submucosal tumors of the colon. The tumor series included seven leiomyomas, one granular-cell myoblastoma, two leiomyosarcomas, seven carcinoid tumors, six lipomas, one lymphangioma, and one neurofibroma. Five of the tumors were asymptomatic. The endoscopic appearances of the tumors, although not diagnostic, may give some indications as to their natures. Endoscopic removal is possible, although it is indicated for high-risk patients only. Because submucosal tumors may be malignant, and because differentiation from secondary tumors (metastases) or tumor-like lesions is difficult without histologic examination, complete removal of the tumor is the treatment of choice.


Radiotherapy Dose in Patients Receiving Immunotherapy.
There is significant rationale for combining radiation therapy (RT) and immuno-oncology (IO) agents, but the optimal radiation parameters are unknown. This review summarizes key trials in the RT and IO space with a focus on RT dose. Very low RT doses solely modulate the tumor immune microenvironment, intermediate doses both modulate the tumor immune microenvironment and kill some fraction of tumor cells, and ablative doses eliminate the majority of target tumor cells and also possess immunomodulatory effects. Ablative RT doses may have high toxicity if targets are adjacent to radiosensitive normal organs. The majority of completed trials have been conducted in the setting of metastatic disease and direct RT to a single lesion with the goal of generating systemic antitumor immunity termed the abscopal effect. Unfortunately, reliable generation of an abscopal effect has proved elusive over a range of radiation doses. Newer trials are exploring the effects of delivering RT to all or most sites of metastatic disease, with dose personalization based on the number and location of lesions. Additional directions include testing RT and IO in earlier stages of disease, sometimes in further combination with chemotherapy and surgery, where lower doses of RT may still contribute substantially to pathologic responses.


Colocalization of tight junction proteins, occludin and ZO-1, and glucose transporter GLUT1 in cells of the blood-ocular barrier in the mouse eye.
The facilitative glucose transporter GLUT1 is abundant in cells of the blood-ocular barrier and serves as a glucose transport mechanism in the barrier. To see the relationship between the glucose transfer function and junctional proteins in the barrier, we examined the localization of GLUT1 and the tight junction proteins, occludin and ZO-1, in the mouse eye. Their localization in the retina, ciliary body, and iris was visualized by double-immunofluorescence microscopy and immunogold electron microscopy. Occludin and ZO-1 were colocalized at tight junctions of the cells of the barrier: retinal pigment epithelial cells, non-pigmented epithelial cells of the ciliary body, and endothelial cells of GLUT1-positive blood vessels. Occludin was restricted to these cells of the barrier. ZO-1 was found, in addition, in sites not functioning as a barrier: the outer limiting membrane in the retina, in the cell border between pigmented and non-pigmented epithelial cells in the ciliary body, and GLUT1-negative blood vessels. These observations show that localization of occludin is restricted to tight junctions of cells of the barrier, whereas ZO-1 is more widely distributed.


The effect of repeated doses of toltrazuril on coccidial oocyst output and weight gain in suckling lambs.
Coccidial oocyst output and liveweight were monitored in 43 pairs of lamb twins over a 10-week period during September-November 1992. One of each set of twins was treated orally with toltrazuril (20 mg/kg) weekly while the other was an untreated control. The oocyst output was significantly lower (P < 0.01) and the weight gain over the trial period was significantly greater (P < 0.05) in the treated group than in the control group.


Anti-Hebbian plasticity in the motor cortex promotes defensive freezing.
Regional brain activity often decreases from baseline levels in response to external events, but how neurons develop such negative responses is unclear. To study this, we leveraged the negative response that develops in the primary motor cortex (M1) after classical fear learning. We trained mice with a fear conditioning paradigm while imaging their brains with standard two-photon microscopy. This enabled monitoring changes in neuronal responses to the tone with synaptic resolution through learning. We found that M1 layer 5 pyramidal neurons (L5 PNs) developed negative tone responses within an hour after conditioning, which depended on the weakening of their dendritic spines that were active during training. Blocking this form of anti-Hebbian plasticity using an optogenetic manipulation of CaMKII activity disrupted negative tone responses and freezing. Therefore, reducing the strength of spines active at the time of memory encoding leads to negative responses of L5 PNs. In turn, these negative responses curb M1's capacity for promoting movement, thereby aiding freezing. Collectively, this work provides a mechanistic understanding of how area-specific negative responses to behaviorally relevant cues can be achieved.


Lung cancer and renal insufficiency: prevalence and anticancer drug issues.
The Renal Insufficiency and Anticancer Medications (IRMA) study reported the high prevalence of renal insufficiency in cancer patients. In this special report, we focused on patients with lung cancer, emphasizing some specific findings in this population of patients. Data on patients with lung cancer who were in the IRMA study were analyzed. Renal function was calculated using Cockcroft-Gault and abbreviated Modification of Diet in Renal Disease (aMDRD) formulas to estimate the prevalence of renal insufficiency (RI) according to the KDOQI-KDIGO definition. Anticancer drugs were studied with regard to their potential renal toxicity and need for dosage adjustment. Of the 445 IRMA lung cancer patients, 14.4% had a serum creatinine (SCR) level > or =110 micromol/L. However, when they were assessed using the formulas, 62.1 and 55.9% had abnormal renal function. Of the 644 anticancer drug prescriptions, 67.5% required dose adjustments for RI or were drugs with no available data, and 78.3% of the patients received at least one such drug. Furthermore, 71.6% received potentially nephrotoxic drugs. Seventy percent of the patients had anemia but prevalence was not significantly associated with the existence of associated renal insufficiency. In the 445 IRMA patients with lung cancer, the prevalence of RI was high in spite of a normal SCR in most cases. Some anticancer drugs such as platinum salts may be nephrotoxic and need dosage adjustment. However, other important drugs such as gemcitabine do not require dose reduction and do not present with a high potential for nephrotoxicity. Lung cancer patients often present with anemia, which was not associated with the presence of RI.


Use of different inhalation devices in children.
Many studies in which patient's inhaler use technique has been studied have shown that one of the major problems patients have, in using an inhaler correctly, is that of poor coordination of inhaler actuation with inspiration. We have studied a new breath-actuated inhaler ("Autohaler" 3M Riker) which is designed to ensure correct coordination automatically. This study involves 100 children (aged 3-10 years) and includes both normal children and asthmatic patients. None of these children have previous experience using any type of inhaler. Each child is taught to use the "Autohaler" containing a placebo only. A video film is employed in order to standardize the teaching technique. Once the child is able to operate the new inhaler correctly, he or she inspires through an "Autohaler" unit specially modified so that the inspiratory flow rate and the volume of air inhaled is measured by a pneumotachograph in series with the inhaler. The time point, within the inspiratory cycle, at which the inhaler is triggered is also recorded. The majority of children older than 7 years were able to use the "Autohaler" after a few minutes instruction. Therefore, this is a valuable alternative in this age group.


[Clinical experiences of bronchopleural fistula-related fatal hemoptysis after the resection of lung cancer: a report of 7 cases].
Massive hemoptysis was a rare but severe postoperative complication of lung cancer. The aim of the present study is to investigate the mechanisms, risk factors, early symptoms, prevention, and treatment options for fatal hemoptysis. From April 2007 to May 2011, 1,737 patients with lung cancer were surgically treated in the West China Hospital of Sichuan University. Twenty patients died during the perioperative period, seven of whom died of massive hemoptysis. These seven cases were analyzed, and their clinical data, as well as related literatures, were reviewed. Massive hemoptysis is the second cause of death after lung cancer surgery. Six patients died directly of massive hemoptysis. One patient underwent secondary surgery because of massive hemoptysis, but eventually died because of lung infection and respiratory failure. Early symptoms of hemorrhage were observed in four cases, and the overall incidence rate of massive hemoptysis was 0.4% (7/1,737). Bronchovascular fistula (BVF) caused by bronchopleural fistula (BPF) is the mechanism for massive hemoptysis. Diabetes is a high risk factor. Early diagnosis and surgical treatment of BPF or BVF can prevent the occurrence of death as a result of massive hemoptysis.


Bystander apoptosis in human cells mediated by irradiated blood plasma.
Following exposure to high doses of ionizing radiation, due to an accident or during radiotherapy, bystander signalling poses a potential hazard to unirradiated cells and tissues. This process can be mediated by factors circulating in blood plasma. Thus, we assessed the ability of plasma taken from in vitro irradiated human blood to produce a direct cytotoxic effect, by inducing apoptosis in primary human peripheral blood mononuclear cells (PBM), which mainly comprised G(0)-stage lymphocytes. Plasma was collected from healthy donors' blood irradiated in vitro to 0-40Gy acute γ-rays. Reporter PBM were separated from unirradiated blood with Histopaque and held in medium with the test plasma for 24h at 37°C. Additionally, plasma from in vitro irradiated and unirradiated blood was tested against PBM collected from blood given 4Gy. Apoptosis in reporter PBM was measured by the Annexin V test using flow cytometry. Plasma collected from unirradiated and irradiated blood did not produce any apoptotic response above the control level in unirradiated reporter PBM. Surprisingly, plasma from irradiated blood caused a dose-dependent reduction of apoptosis in irradiated reporter PBM. The yields of radiation-induced cell death in irradiated reporter PBM (after subtracting the respective values in unirradiated reporter PBM) were 22.2±1.8% in plasma-free cultures, 21.6±1.1% in cultures treated with plasma from unirradiated blood, 20.2±1.4% in cultures with plasma from blood given 2-4Gy and 16.7±3.2% in cultures with plasma from blood given 6-10Gy. These results suggested that irradiated blood plasma did not cause a radiation-induced bystander cell-killing effect. Instead, a reduction of apoptosis in irradiated reporter cells cultured with irradiated blood plasma has implications concerning oncogenic risk from mutated cells surviving after high dose in vivo irradiation (e.g. radiotherapy) and requires further study.


Natural insect host-parasite systems show immune priming and specificity: puzzles to be solved.
Study of the multiplicity of interactions between invertebrate hosts and their parasites helps to define the aspects of the host immune systems that have ecological and evolutionary significance. Such study, however, reveals how much is yet unknown. For instance, the costs of mounting an immune response, the nature of the long-lasting protection sometimes attained, and the high degree of specificity observed in certain hosts are phenomena that still await full explanation. An additional puzzle is the high degree of specificity achieved in light of the apparent low degree of specificity in the recognition and effector mechanisms of insect immune systems. Furthermore, while protective immunity is typically associated with vertebrate adaptive immune systems, invertebrates may have analogous capacities, whose nature is still largely unknown. This review will illustrate how the traditional host-centred view of immune defence can be usefully extended by taking account of parasite immune evasion strategies and the variation that such strategies create in the observed outcomes of infection.


Tempol (4 hydroxy-tempo) inhibits anoxia-induced progression of mitochondrial dysfunction and associated neurobehavioral impairment in neonatal rats.
Anoxia leads to a robust generation of reactive oxygen species/nitrogen species which can result in mitochondrial dysfunction and associated cell death in the cerebral cortex of neonates. The present study investigated the pharmacological role of tempol in the treatment of rat neonatal cortical mitochondrial dysfunction induced insult progression (day-1 to day-7) and associated neurobehavioral alterations post-anoxia. Rat pups of 30h age or postnatal day 2 (PND2) were randomly divided into 5 groups (n=5 per group): (1) Control; (2) Anoxia; (3) Anoxia+Tempol 75mg/kg; (4) Anoxia+Tempol 150mg/kg; and (5) Anoxia+Tempol 300mg/kg, and subjected to two episode of anoxia (10min each) at 24h of time interval in an enclosed chamber supplied with 100% N2. Tempol significantly decreased nitric oxide (NO) formation and simultaneously improved superoxide dismutase (SOD) and catalase (CAT) activities. Further, we observed a significantly (P<0.05) improvement in mitochondrial respiration, complex enzyme activities, mitochondrial membrane potential (MMP) along with attenuation of transition pore opening (MPT) after treatment with tempol. Furthermore, tempol decreased expression of mitochondrial Bax, cytochrome-C, caspase-9 and caspase-3 while the increase in expression of cytoplasmic Bax, mitochondrial Bcl-2 on day-7 in cortical region indicating regulation of intrinsic pathway of apoptosis. Further, it improved anoxia-induced neurobehavioral outcome (hanging and reflex latencies). Biochemical, molecular and behavioral studies suggest the role of tempol in preserving mitochondrial function and associated neurobehavioral outcomes after neonatal anoxia.


Pentosan polysulfate as an inhibitor of calcium oxalate crystal growth.
Pentosan polysulfate was studied as a calcium oxalate crystal growth inhibitor. The inhibition from pentosan polysulfate at concentrations ranging from 3.5 to 110 mg./l. was measured in simple inorganic calcium oxalate solutions at pH 5, 6 and 7. Pentosan polysulfate also was mixed with urine at concentrations from 10 to 350 mg./l. and inhibition determined. Measurement of calcium oxalate crystal growth inhibition was performed in a seeded crystal growth system. One inhibitory unit (concentration of pentosan polysulfate necessary to give a 50 per cent reduction in the rate of crystal growth) was 5.7 +/- 2 mg./l. at pH 5, 7.2 +/- 1.1 mg./l. at pH 6 and 6.0 +/- 2.1 mg./l. at pH 7. Urine-pentosan polysulfate mixtures showed more inhibitory activity than the predicted inhibition present. Addition of pentosan polysulfate to urine at a concentration of 10 mg./l. increased the inhibitory activity from 45 +/- 3 to 59 +/- 3 IU/l. Pentosan polysulfate is a potent calcium oxalate crystal growth inhibitor in urine at physiologic pH levels. If the urinary concentration of pentosan polysulfate after oral administration reaches 10 mg./l., the increase in inhibitory activity in urine that may occur might be important in the treatment of patients who form calcium oxalate calculi within the urinary tract.


Scaphoid nonunions in adolescents: Treatment with vascularized bone grafts.
Scaphoid nonunions (SN) are rare in adolescents. The use of vascularized bone grafts (VBG) from the distal radius as an alternative to conventional grafting for the treatment of established SN in adolescents is described. The technique was applied in 13 patients with symptomatic SN resulting from fractures. All patients were male with average age of 16.5 years (15-17.5). The average period from injury to surgery was 8.3 months (4-13). Patients underwent vascularized bone grafting and internal fixation with K-wires. In 6 patients with proximal pole nonunion a VBG from the dorsal distal radius was used, and in 7 with a waist nonunion a VBG from the palmar distal radius was used. The valuation was clinical (grip strength, range of motion, VAS pain score, DASH) and radiographic. The time to return to activity was also recorded. The mean follow-up was 9.8 years (range, 4-16). The union rate was 100% (11/11 cases). Union was achieved in a mean period of 7.2 weeks (range, 6-10), without growth disturbance or other complications from the epiphyseal plate of the distal radius. The range of motion and grip strength was 89% and 92% of the contralateral respectively. The mean postoperative DASH score was 8 and the VAS score was 1. All patients returned to daily activities and sports in a mean period of 4.5 months. The use of VBG from the distal radius provided a permanent solution in the rare case of SN in adolescents, without donor site morbidity or epiphyseal plate disturbance. The deformity and carpal height were corrected resulting in painless motion and grip strength.