Design, synthesis and mechanistic studies of novel imidazo[1,2-a]pyridines as anticancer agents.

Herein, the design, synthesis and mechanistic study of five series of imidazo[1,2-a]pyridines 8a-d, 9a-f, 11a-c, 12a-d and 14a-d as anticancer agents were discussed. The cytotoxicity of imidazo[1,2-a]pyridine derivatives was screened against NCI 60 cancer cell lines. The cytotoxicity of compounds 8b, 8c, 9e and 9f was then evaluated against leukemia K-562 cancer cell line and normal lung fibroblasts (WI38). The hydrazone derivatives 8b and 8c exhibited significant cytotoxic activities against the leukemia K-562 cancer cell line with good safety margins (IC50 = 2.91 µM, SI = 8.32 and IC50 = 1.09 µM, SI = 10.54, respectively). In addition, compounds 8b, 8c, 9e and 9f were tested for their EGFR and COX-2 inhibitory activities. The hydrazone derivatives 8b and 8c were the most active EGFR inhibitors with IC50 values of 0.123 and 0.072 µM, respectively. Compound 8c selectively inhibited COX-2 (IC50 = 1.09 µM, SI = 13.78). Moreover, the potential of compound 8c to induce apoptosis in leukemia K-562 cell line was determined. Compound 8c showed a pre-G1 apoptosis and a growth arrest of leukemia K-562 cell line at G1 phase of cell cycle. Also, compound 8c was able to induce caspase-3 overexpression (6.98 folds), if compared to control. Finally, molecular docking studies and physicochemical properties calculation of compounds 8b, 8c, 9e and 9f were carried out to explain the biological data and to predict bioavailability of the most active compounds.

Design, synthesis and molecular docking of new fused 1H-pyrroles, pyrrolo[3,2-d]pyrimidines and pyrrolo[3,2-e][1, 4]diazepine derivatives as potent EGFR/CDK2 inhibitors.

A new series of 1H-pyrrole (6a-c, 8a-c), pyrrolo[3,2-d]pyrimidines (9a-c) and pyrrolo[3,2-e][1, 4]diazepines (11a-c) were designed and synthesised. These compounds were designed to have the essential pharmacophoric features of EGFR Inhibitors, they have shown anticancer activities against HCT116, MCF-7 and Hep3B cancer cells with IC50 values ranging from 0.009 to 2.195 µM. IC50 value of doxorubicin is 0.008 µM, compounds 9a and 9c showed IC50 values of 0.011 and 0.009 µM respectively against HCT-116 cells. Compound 8b exerted broad-spectrum activity against all tested cell lines with an IC50 value less than 0.05 µM. Compound 8b was evaluated against a panel of kinases. This compound potently inhibited CDK2/Cyclin A1, DYRK3 and GSK3 alpha kinases with 10-23% compared to imatinib (1-10%). It has also arrested the cell cycle of MCF-7 cells at the S phase. Its antiproliferative activity was further augmented by molecular docking into the active sites of EGFR and CDK2 cyclin A1.

Design & synthesis of novel oxazolone & triazinone derivatives and their biological evaluation as COX-2 inhibitors.

A new series of oxazolones and triazinones were designed and synthesized and evaluated against both COX-1 and COX-2 enzymes. Full structure elucidation of the new derivatives was performed using microanalyses, IR, 1H NMR, 13C NMR and mass spectra. Most of the derivatives showed good inhibitory activity against COX-2 enzyme specifically compounds IIIc, IIIe, IVd and IVg with IC50 values 0.024, 0.019, 0.011 and 0.014µM compared to celecoxib as reference drug with IC50 value of 0.05µM. Altogether, these results indicate that these derivatives can be effective anti-inflammatory agents.

Improving genetic evaluation using a multitrait single-step genomic model for ability to resume cycling after calving, measured by activity tags in Holstein cows.

The objective of this study was to evaluate the improvement of the accuracy of estimated breeding values for ability to recycle after calving by using information of genomic markers and phenotypic information of correlated traits. The traits in this study were the interval from calving to first insemination (CFI), based on artificial insemination data, and the interval from calving to first high activity (CFHA), recorded from activity tags, which could better measure ability to recycle after caving. The phenotypic data set included 1,472,313 records from 820,218 cows for CFI, and 36,504 records from 25,733 cows for CFHA. The genomic information was available for 3,159 progeny-tested sires, which were genotyped using Illumina Bovine SNP50 BeadChip (Illumina, San Diego, CA). Heritability estimates were 0.06 for the interval from calving to first insemination and 0.14 for the interval from calving to first high activity, and the genetic correlation between both traits was strong (0.87). Breeding values were obtained using 4 models: conventional single-trait BLUP; conventional multitrait BLUP with pedigree-based relationship matrix; single-trait single-step genomic BLUP; and multitrait single-step genomic BLUP model with joint relationship matrix combining pedigree and genomic information. The results showed that reliabilities of estimated breeding values (EBV) from single-step genomic BLUP models were about 40% higher than those from conventional BLUP models for both traits. Furthermore, using a multitrait model doubled the reliability of breeding values for CFHA, whereas no gain was observed for CFI. The best model was the multitrait single-step genomic BLUP, which resulted in a reliability of EBV 0.19 for CFHA and 0.14 for CFI. The results indicate that even though a relatively small number of records for CFHA were available, with genomic information and using multitrait model, the reliability of EBV for CFHA is acceptable. Thus, it is feasible to include CFHA in Nordic Holstein breeding evaluations to improve fertility performance.

Seasonality of fertility measured by physical activity traits in Holstein cows.

Seasonality of female fertility traits, including the interval from calving to first high activity (CFHA), duration of high activity episode (DHA), and strength of high activity episode (SHA) of first estrus, were studied. The physical activity traits were derived from electronic activity tags for 20,794 Holstein cows in 135 commercial Holstein herds in Denmark. Data were categorized in 3 ways: (1) into 4 seasons of calving: winter (January-March), spring (April-June), summer (July-September), and fall (October-December); (2) into 2 seasons: a cold season (October-March) and a warm season (April-September); and (3) into an increasing light season (IL; January-June), where daylight hours gradually increased, and a decreasing light season (DL; July-December), where daylight hours gradually decreased. At the phenotypic level, least squares means of CFHA were highest at 55d for cows calving in December and lowest at 31d for cows calving in September. The highest least squares means of DHA and SHA were recorded for cows calving in November and lowest for cows calving in May and June. Genetic parameters for all traits were estimated using average information-REML in a bivariate animal model that treated the same trait in different calving seasons as different traits. Heritability estimates for CFHA were highest for the winter season (0.13) and low for the other seasons (0.03-0.04), whereas heritability estimates for DHA and SHA were lowest for winter and highest for fall. Heritability estimates for CFHA for the cold season (0.17) was higher than that for the warm season (0.10). Heritability estimates of CFHA for the IL season (0.12) was higher than for the DL season (0.07), but the opposite pattern was found for DHA and SHA. Genetic correlations (rA) of CFHA between winter and summer (rA=0.34 ± 0.27), and winter and fall (rA=0.65 ± 0.20) were significantly lower than unity. The corresponding correlations of DHA and SHA between seasons were all close to unity, except for the correlation of SHA between winter and fall (rA=0.36 ± 0.34). When the year was split into only 2 seasons, the genetic correlation of CFHA between cold and warm seasons was only moderate (rA=0.46 ± 0.15) but was slightly stronger between IL and DL seasons (rA=0.63 ± 0.16); both significantly deviated from unity. These results indicate the existence of a genotype by environment interaction for CFHA regardless of calving season classification.

Genotype by environment interaction for activity-based estrus traits in relation to production level for Danish Holstein.

The objective of this study was to investigate whether genotype by environment interaction exists for female fertility traits and production of energy-corrected milk at 70d in milk (ECM70). Fertility traits considered were the activity-based estrus traits interval from calving to first high activity (CFHA), duration of high activity episode (DHA), as an indicator for first estrus duration, and strength of high activity episode (SHA), as an indicator for first estrus strength. The physical activity traits were derived from electronic activity tags for 11,522 first-parity cows housed in 125 commercial dairy herds. Data were analyzed using a univariate random regression animal model (URRM), by regressing the phenotypic performance on the average herd ECM70 as an environmental gradient. Furthermore, the genetic correlations between CFHA and ECM70 as a function of production level were estimated using a bivariate random regression animal model (BRRM). For all traits, heterogeneity of additive genetic variances and heritability estimates was observed. The heritability estimate for CFHA decreased from 0.25 to 0.10 with increasing production level and the heritability estimate for ECM70 decreased from 0.35 to 0.15 with increasing production level using URRM. The genetic correlation of the same trait in low and high production levels was around 0.74 for CFHA and 0.80 for ECM70 using URRM, but when data were analyzed using the multiple-trait analysis (MT), genetic correlation estimates between low and high production levels were not significantly different from unity. Furthermore, the genetic correlation of SHA between low and high production level was 0.22 using URRM, but the corresponding correlation estimate had large standard error when data were analyzed using MT. The genetic correlation between CFHA and ECM70 as a function of production environment was weak but unfavorable and decreased slightly from 0.09 to 0.04 with increasing production level using BRRM. Moreover, the same trend was observed when the data were analyzed using MT where the genetic correlation between CFHA and ECM70 in the low production environment was 0.29 compared with -0.13 in the high production environment, but these estimates had large standard errors. In conclusion, regardless of the trait used, in relation to average herd ECM70 production, the results indicated no clear evidence of strong genotype by environment interaction that would cause significant re-ranking of sires between low and high production environments.

Genotype by environment interaction for the interval from calving to first insemination with regard to calving month and geographic location in Holstein cows in Denmark and Sweden.

The objectives of this study were to investigate genotype by environment interaction effects, with environments defined as calving month and geographic location, on the interval from calving to first insemination (CFI) of Holstein cows in Denmark and Sweden. The data set included 811,285 records on CFI for first-parity cows from January 2010 to January 2014 housed in 7,458 herds. The longest mean CFI was 84.7 d for cows calving in April and the shortest was 76.3 d for cows calving in September. The longest mean CFI of 87.1 d was recorded at the northernmost location (LOC-8), whereas the shortest mean CFI of 73.5 d was recorded at the southernmost location (LOC-1). The multiple trait approach, in which CFI values in different calving months and different geographic locations were treated as different traits, was used to estimate the variance components and genetic correlations for CFI by using the average information (AI)-REML procedure in a bivariate sire model. Estimates of genetic variance and heritability were highest for January calvings and 3 times smaller for June calvings. Location 2 had the highest heritability and LOC-8 the lowest, with heritability estimates decreasing from LOC-2 to LOC-8. Genetic correlations of CFI between calving months were weakest between cold months (December and January) and warm months (June, August, and September); the lowest estimate was found between January and September calvings. Genetic correlations of CFI between the different geographic locations were generally strong, and the weakest correlation was between LOC-3 and LOC-8. These results indicate a genotype by environment interaction for CFI primarily regarding seasons described by calving months. The effect of geographic location was less important, mostly producing a scaling effect of CFI in different locations. We concluded that CFI is more sensitive to seasonal effects than geographic locations in Denmark and Sweden.

Estrus traits derived from activity measurements are heritable and closely related to the time from calving to first insemination.

The aim of this study was to estimate genetic parameters for estrus-related traits that could improve selection for increased fertility due to improved ability of the cow to return to cycling and go into heat after calving. We compared the time from calving to first insemination (CFI) to 3 physical activity traits: the interval from calving to first high activity (CFHA), estrus duration (ED), and estrus strength (ES). We calculated CFI based on data from commercial Holstein herds that included the insemination dates for 11,363 cows. The CFHA, ED, and ES traits were derived from electronic activity tags for 3,533 Holstein cows. Estimates of heritability were 0.07 for CFI, 0.16 for CFHA, 0.02 for ED, and 0.05 for ES. We found a strong genetic correlation between CFI and CFHA (0.96). Genetic correlations between ED and CFI and CFHA were -0.37 and -0.68, respectively. Genetic correlations between ES and CFI and CFHA were -0.50 and -0.58, respectively. The heritability of CFHA and its strong genetic correlation with CFI suggest that including CFHA in the genetic evaluation of female cow fertility could improve the effectiveness of selection, because CFHA reflects the ability to return to cyclicity and go into heat after calving.

Competitive capabilities of higher education institutions from their Employees' perspectives: A case study of King Khalid University.

This study aimed to uncover the competitive advantages of King Khalid University (KKU) as a higher educational institution and identify the strategies needed to strengthen its competitive stance through a qualitative case study approach. Data were collected via detailed interviews with 30 university staff, comprising 19 faculty members and 11 academic leaders. Following this, the data were qualitatively analyzed using MAXQDA 2022 software. The results showed that KKU has 30 sub-competitive strengths, including work ethics, future vision, academic excellence, creativity, teamwork, respect for intellectual property, continuous customer-focused improvement, a positive workplace environment, organizational trust, and the ability to attract international students. Additionally, the study identified 8 challenges hindering KKU's advancement in global university rankings, spanning academic, human, and administrative areas. To improve its standing in international rankings, thematic analysis revealed 11 strategies to enhance KKU's competitiveness. These include aligning academic programs with job market demands, enhancing research facilities, boosting funding for academic and research endeavors, fostering international academic and scientific partnerships, and upgrading the technological infrastructure for academics and administration. The analysis underscores the need for KKU to adopt a comprehensive suite of academic, human, and administrative strategies to bolster its competitive position. This is crucial for KKU's rise in global university rankings and its alignment with the National Vision 2030, aiming to place over five Saudi universities among the top 100 or 200 globally.

Protein supplement intake by non-athlete gym attendees in Jazan region: misconceptions and gender differences.

BACKGROUND: Protein supplements (PSs) have gained widespread popularity among non-athlete gym attendees, who often perceive them as essential tools for muscle growth and recovery. However, misinformation surrounding PSs may lead to inappropriate use and negative health consequences. This study aimed to assess whether non-athlete gym attendees using PSs have greater misconceptions than non-users while also examining the prevalence of PS consumption and gender differences. METHODS: A cross-sectional study of 387 participants in the Jazan region was conducted. Customers of 10 fitness centers were screened with a questionnaire comprising questions to measure PS misconceptions. Participants were divided into PS users and non-users. Data were analyzed using descriptive statistics and the Chi-square test to assess the associations between variables. An independent t-test was used to compare the PS Misconception Index Score between the two groups. RESULTS: A total of 82.4% of non-athlete gym attendees consumed at least one PS. Our findings revealed a significant association between gender and PS utilization (P<0.001), with a higher proportion of females (90.8%) consuming PS than males (77.6%). PS users had a significantly lower PS Misconception Index Score than non-users (26.8 vs. 28.3; P=0.006), indicating that PS users had a higher number of misconceptions. The internet (41.37%) and coaches (gym instructors/trainers) (34.48%) were the most common sources of information about PSs, with muscle gain being the primary reason for consumption (82.75%). CONCLUSIONS: PS consumption is highly prevalent among non-athlete gym attendees in the Jazan region, with many individuals having misconceptions about their benefits and potential risks. Targeted educational interventions are needed to promote evidence-based knowledge about PSs for gym attendees, as well as for coaches, given that they were among the primary sources of information on supplements.

Mapping the evidence on integrated service delivery for non-communicable and infectious disease comorbidity in sub-Saharan Africa: protocol for a scoping review.

INTRODUCTION: The concurrent occurrence of infectious diseases (IDs) and non-communicable diseases (NCDs) presents complex healthcare challenges in sub-Saharan Africa (SSA), where healthcare systems often grapple with limited resources. While an integrated care approach has been advocated to address these complex challenges, there is a recognised gap in comprehensive evidence regarding the various models of integrated care, their components and the feasibility of their implementation. This scoping review aims to bridge this gap by examining the breadth and nature of evidence on integrated care models for NCDs and IDs within SSA, thereby updating the current evidence base in the domain. METHODS AND ANALYSIS: Based on the Joanna Briggs Institute (JBI) framework for scoping reviews, this study will include peer-reviewed and grey literature reporting on integrated care models for NCD-ID comorbidities in SSA. A comprehensive search of published sources in electronic databases (PubMed, Scopus, Embase, the Cochrane Library, Health System Evidence and Research4Life) and grey literature (Google Scholar, EBSCO Open Dissertations and relevant organisational websites) will be conducted to identify sources of information reported in English from 2018 onwards. The review will consider sources of evidence reporting on integrated care model for NCDs such as diabetes; chronic cardiovascular, respiratory and kidney diseases; cancers; epilepsy; and mental illness, and comorbid IDs such as HIV, tuberculosis and malaria. All sources of evidence will be considered irrespective of the study designs or methods used. The review will exclude sources that solely focus on the differentiated or patient-centred care delivery approach, and that focus on other conditions, populations or settings. The reviewers will independently screen the sources for eligibility and extract data using a JBI-adapted data tool on the Parsifal review platform. Data will be analysed using descriptive and thematic analyses and results will be presented in tables, figures, diagrams and a narrative summary. ETHICS AND DISSEMINATION: Ethical approval is not required for this review as it will synthesise published data and does not involve human participants. The final report will be submitted for publication in a peer-reviewed journal. The findings will be used to inform future research. STUDY REGISTRATION: OSF: https://doi.org/10.17605/OSF.IO/KFVEY.

Intralesional purified protein derivative versus zinc sulfate 2% in the treatment of pediatric warts: Clinical and dermoscopic evaluation.

BACKGROUND: Warts are common in children and can be difficult to treat. Many treatments for warts are destructive and painful in contrast to intralesional immunotherapy using different types of antigens. AIM: To evaluate the efficacy, safety, and tolerability of intralesional purified protein derivative (PPD) versus intralesional zinc sulfate 2% in the treatment of pediatric warts. METHODS: This randomized clinical trial included 120 children with multiple warts divided into two equal groups. Group Ⅰ received intralesional 10 IU (0.1 ml) of PPD, group Ⅱ received intralesional zinc sulfate 2% in the largest wart every 2 weeks till improvement or for a maximum five treatment sessions. The follow-up period was 6 months after the last treatment session. RESULTS: The overall response was equal in both groups (81.7%), but the response of the injected wart was higher in the zinc sulfate group (93.4%) versus PPD group (83.3%) with no significant difference. The highest cure rates were after the 5th session in the PPD group and the 1st session in the zinc sulfate group with slightly lower numbers of sessions needed for cure in the zinc sulfate group (3 sessions) versus the PPD group (4 sessions). The zinc sulfate group showed statistically significant higher rates of complications (pain, inflammation, necrosis, and scar) than PPD group. The zinc sulfate group showed non-significant higher rates of recurrence during the follow-up period. CONCLUSION: Both intralesional PPD and zinc sulfate 2% are effective in pediatric warts with higher safety profile of PPD.

Perceived impact of COVID-19 on routine care of patients with chronic non-communicable diseases: a cross-sectional study.

Introduction: patients with chronic non-communicable diseases (chronic liver diseases, chronic respiratory diseases, neurologic diseases, chronic kidney diseases, cardiovascular diseases, diabetes mellitus, and hypertension), primarily poor, rural and neglected populations, have had difficulty accessing health care and have been severely impacted both socially and financially in during the pandemic. As a result, this study was designed to assess the perceived impact of COVID-19 on routine care of chronic non-communicable disease patients in Ethiopia. Methods: a cross-section survey was conducted among 404 participants from April 1st 2021 to May 30th 2021. Data were collected via interviewer administered questionnaires administered by pre-tested interviewers on socio-demographic characteristics, treatment and clinical features and routine care questionnaires that have been adapted and modified from different literatures. The study consisted of all adult outpatients with at least one chronic non-communicable disease who were followed up. Data were analyzed using the Statistical Package for Social Sciences Version 23. Results: of the 422 participants, 404 responded for a response rate of 95.7%. One out of two (203, 50.2%) participants was aged 40 to 50 years. Ninety-one out of hundred (367, 90.8%) participants continued to receive routine care face-to-face during COVID-19. One-third (141, 34.9%) of study participants had good management of the chronic non-communicable diseases care in the middle of pandemic. A total of 167(41.34%) participants thought they were moderately affected changes in healthcare services since the COVID-19 outbreak. Nearly one-third (130, 32.2%) of participants were sometimes affected by medication shortages since the start of COVID-19. Conclusion: this study highlights that most participants continued to receive routine care face-to-face during the COVID-19. About forty-one out of 100 participants perceived that they were moderately affected changes in healthcare services since the outbreak of COVID-19. One-third of participants sometimes perceived that they were affected by medication shortages since the start of COVID-19.

Genetic Variation for Economically Important Traits in Cupressus lusitanica in New Zealand.

Increasing productivity and tolerance against cypress canker disease is an important goal in the Mexican white cypress breeding program in New Zealand, and screening has been in place since 1983. Cypress canker disease is caused by Seiridium cardinale and Seiridium cupressi, the current study presents the results of two progeny trials within the breeding program in the North Island of New Zealand. The trials were established as open-pollinated progeny tested and were assessed for diameter at breast height, branch size, canker severity score, malformation score, and stem straightness score and acceptability score. Heritability estimates were moderate ranging from 0.21 to 0.41 for diameter at breast height and from 0.14 to 0.31 for canker severity score. Stem form attributes showed heritability from 0.08 (malformation) to 0.38 (straightness). No trait showed any significant G × E interaction between investigated sites. This was supported by the very strong genetic correlations estimated between the traits recorded in Welcome Bay and Matata trials. Unfavourable genetic correlations ranging from 0.25 to 0.46 were found between diameter at breast height and canker severity score, indicating that the continued selection for genotypes with improved diameter at breast height would also increase susceptibility to cypress canker. Additionally, unfavourable genetic correlations ranging from 0.52 to 0.73 were found between branch size and diameter at breast height and should be considered in selection programs. The moderate heritability estimated for canker severity score indicates that breeding values for this trait could be predicted with acceptable accuracy and included in the breeding program for Cupressus lusitanica, enabling the identification of genotypes with tolerance to canker severity to be deployed to locations where cypress canker is present in New Zealand.

Genetic Variation in Drought-Tolerance Traits and Their Relationships to Growth in Pinus radiata D. Don Under Water Stress.

The selection of drought-tolerant genotypes is globally recognized as an effective strategy to maintain the growth and survival of commercial tree species exposed to future drought periods. New genomic selection tools that reduce the time of progeny trials are required to substitute traditional tree breeding programs. We investigated the genetic variation of water stress tolerance in New Zealand-grown Pinus radiata D. Don using 622 commercially-used genotypes from 63 families. We used quantitative pedigree-based (Genomic Best Linear Unbiased Prediction or ABLUP) and genomic-based (Genomic Best Linear Unbiased Prediction or GBLUP) approaches to examine the heritability estimates associated with water stress tolerance in P. radiata. Tree seedling growth traits, foliar carbon isotope composition (δ13C), and dark-adapted chlorophyll fluorescence (Y) were monitored before, during and after 10 months of water stress. Height growth showed a constant and moderate heritability level, while the heritability estimate for diameter growth and δ13C decreased with water stress. In contrast, chlorophyll fluorescence exhibited low heritability after 5 and 10 months of water stress. The GBLUP approach provided less breeding value accuracy than ABLUP, however, the relative selection efficiency of GBLUP was greater compared with ABLUP selection techniques. Although there was no significant relationship directly between δ13C and Y, the genetic correlations were significant and stronger for GBLUP. The positive genetic correlations between δ13C and tree biomass traits under water stress indicated that intraspecific variation in δ13C was likely driven by differences in the genotype's photosynthetic capacity. The results show that foliar δ13C can predict P. radiata genotype tolerance to water stress using ABLUP and GBLUP approaches and that such approaches can provide a faster screening and selection of drought-tolerant genotypes for forestry breeding programs.

The impact of timing of maximal crystalloid hydration on early graft function during kidney transplantation.

BACKGROUND: Early graft function is crucial for successful kidney transplantation. Maintaining adequate hydration is complicated by rapid movement of water to the extravascular space. We designed this study to test the effect of maximal hydration during graft ischemia time on early renal function. METHODS: Forty adult patients with chronic renal failure underwent renal transplantation from related living donors. Study subjects were randomly assigned 1 of 2 regimens for intraoperative hydration. The constant infusion rate group received normal saline 0.9% at an infusion rate 10 to 12 mL . kg(-1) . h(-1) from the start of surgery until the renal vessels were unclamped after vascular anastomosis. The central venous pressure target (CVPT) group received normal saline 0.9% titrated to maintain a specific central venous pressure (CVP). The target CVP from the start of surgery until clamping of the donor renal vessels was 5 mm Hg except for the interval from clamping of the renal vessels until the end of renal vascular anastomosis, when the target CVP was 15 mm Hg. Perioperative hemodynamics, infused saline volumes, rate of infusion, onset of diuresis, graft turgidity, urine volume, and renal function during the first 5 postoperative days were recorded. RESULTS: At the end of renal ischemia time, both groups had received approximately 3 L crystalloid solution. The CVPT group achieved the highest peak of intravascular volume expansion with an average infusion rate of 48.3 mL . min(-1) during 48 +/- 12 minutes of renal ischemia. The CVPT group had better graft function, required fewer vasopressors and diuretics, and had less postoperative tissue edema than the constant infusion rate group. CONCLUSIONS: Hydration directed toward maintaining a given CVP during kidney transplantation produced a more stable hemodynamic profile and promoted diuresis. The calculated infusion rate of approximately 45 to 50 mL . min(-1), within an hour ischemia time, seems feasible to enhance early graft function. A larger trial with long-term follow-up of renal function is warranted to confirm the clinical benefit of titrating IV crystalloid administration to maintain a given CVP in this population.

Indication of Quantitative Multiple Disease Resistance to Foliar Pathogens in Pinus radiata D.Don in New Zealand.

Increasing resistance against foliar diseases is an important goal in the Pinus radiata D.Don breeding program in New Zealand, and screening for resistance has been in place for some time, since the late 1960s. The current study presents results of four progeny trials within the breeding program to investigate whether multiple disease resistance could be detected against three different needle diseases in P. radiata: Dothistroma needle blight (DNB) caused by Dothistroma septosporum, Cyclaneusma needle cast (CNC) caused by Cyclaneusma minus, and red needle cast (RNC) caused by Phytophthora pluvialis. Four progeny trials in the North Island of New Zealand were available to estimate heritabilities and between-trait genetic correlations. Two of the trials were assessed for DNB, involving 63 full-sib families. A third trial was assessed for CNC, involving 172 half-sib families, and a fourth trial was assessed for RNC, involving 170 half-sib families. Disease resistances had moderate estimates of heritability (0.28-0.48) in all trials. We investigated the potential for multiple disease resistance to the three foliar diseases by estimating genetic correlations between disease resistances using a spatial linear mixed model. The correlation between DNB and CNC resistance was favorable and strong (0.81), indicating that genotypes that are highly resistant to DNB also have a high resistance to CNC. These results suggest that selection based on resistance to DNB could allow for simultaneous indirect selection for resistance to CNC, usually only expressed at a later age. This would allow selections to be made earlier due to the earlier expression of DNB than CNC and reduce the number of expensive disease assessments being undertaken. Conversely, genetic correlation estimates for RNC with DNB and CNC were close to zero, and very imprecise. As such, later-age assessments for this disease would still be required.

Genome-wide association mapping for dominance effects in female fertility using real and simulated data from Danish Holstein cattle.

Exploring dominance variance and loci contributing to dominance variation is important to understand the genetic architecture behind quantitative traits. The objectives of this study were i) to estimate dominance variances, ii) to detect quantitative trait loci (QTL) with dominant effects, and iii) to evaluate the power and the precision of identifying loci with dominance effect through post-hoc simulations, with applications for female fertility in Danish Holstein cattle. The female fertility records analyzed were number of inseminations (NINS), days from calving to first insemination (ICF), and days from the first to last insemination (IFL), covering both abilities to recycle and to get pregnant in the female reproductive cycle. There were 3,040 heifers and 4,483 cows with both female fertility records and Illumina BovineSNP50 BeadChip genotypes (35,391 single nucleotide polymorphisms (SNP) after quality control). Genomic best linear unbiased prediction (BLUP) models were used to estimate additive and dominance genetic variances. Linear mixed models were used for association analyses. A post-hoc simulation study was performed using genotyped heifers' data. In heifers, estimates of dominance genetic variances for female fertility traits were larger than additive genetic variances, but had large standard errors. The variance components for fertility traits in cows could not be estimated due to non-convergence of the statistical model. In total, five QTL located on chromosomes 9, 11 (2 QTL), 19, and 28 were identified and all of them showed both additive and dominance genetic effects. Among them, the SNP rs29018921 on chromosome 9 is close to a previously identified QTL in Nordic Holstein for interval between first and last insemination. This SNP is located in the 3' untranslated region of gene peptidylprolyl isomerase like 4 (PPIL4), which was shown to be associated with milk production traits in US Holstein cattle but not known for fertility-related functions. Simulations indicated that the current sample size had limited power to detect QTL with dominance effects for female fertility probably due to low QTL variance. More females need to be genotyped to achieve reliable mapping of QTL with dominance effects for female fertility.

Dermatoses among automobile mechanics in Mansoura, Egypt.

This cross-sectional study was carried out in Mansoura, Egypt to assess the prevalence of occupational dermatoses and their possible risk factors on a convenience sample of car mechanics. Sociodemographic and occupational data were collected, and clinical examination was done. Prevalence of skin diseases was 45.4% and that of exclusively occupational skin diseases was 9.2%. Irritant contact dermatitis, eczema, and tar/oil acne were the most common types (4.6%, 3.1%, 3.1%, respectively). The logistic regression analysis revealed that the risk of occupational dermatoses increased significantly with lack of use of personal protective equipment, longer duration of work, and presence of workplace chemicals (adjusted odds ratio [95% CI] were 7.2 [2.7, 19.0], 4.3 [1.7, 10.9], and 3.7 [1.3, 10.5], respectively). Health education and safety measures are essential for prevention and control of hazardous workplace practices and exposure.

Use of the Bonfils Intubation Fiberscope in patients with limited mouth opening.

Airway management of patients with very limited mouth opening remains a challenge for the anaesthetist. We describe the use of the Bonfils Intubation Fiberscope for awake intubation in two patients with a very limited mouth opening. In the first case, a 60-year-old 80 kg female, scheduled for a right modified radical mastectomy for infiltrating ductal carcinoma (15 mm mouth opening, a short thick neck, limited neck extension, and a Mallampati class 4 airway), the Bonfils was advanced via the retromolar technique. In the second patient, a 34-year-old male, scheduled for a surgical tracheotomy for right tonsillar cancer, due to a neoplastic infiltration of the right temporomandibular joint (7 mm mouth opening and limited neck movement), the Bonfils was advanced using the midline approach. The Bonfils is a reusable, rigid, straight fiberoptic device with a curved tip, is 5 mm in diameter, and has several advantages: it is quick and easy to use, more cost effective than a flexible fiberscope, and is safe in expert hands, thanks to its smaller diameter. Our conclusion is that awake BIF intubation is a reliable, atraumatic, and well-tolerated procedure to secure a safe airway in patients with a limited mouth opening.