Characterization of Pepper leafroll chlorosis virus, a New Polerovirus Causing Yellowing Disease of Bell Pepper in Saudi Arabia.

During the growing seasons of 2014 through 2016, a total of 336 leaf samples from bell pepper (showing leafroll and interveinal yellowing) and arable weeds were collected from Riyadh region, Saudi Arabia. The use of a polerovirus generic reverse transcription (RT)-PCR assay confirmed their presence in the bell pepper samples. Sequencing of the generic amplicon revealed high similarity (87.6 to 98.1% in nt) with four poleroviruses; Tobacco vein distorting virus, Pepper vein yellows virus, Pepper yellows virus, and Pepper yellow leaf curl virus. To further characterize one of these isolates (105D), a larger part of the genome (∼1,300 nt) spanning approximately from the 3' end of ORF2 to the middle of ORF3, was amplified and sequenced. Blasting the resulting sequence revealed the low amino acid and nucleotide identity percentages in the coat protein and movement protein partial genes with viruses deposited in GenBank. Next-generation sequence was used to acquire a larger part of the genome, which resulted in the reconstruction of isolate 105D's partial genome (5,496 nt). Sequence similarity analysis revealed the presence of a divergent polerovirus isolate belonging to a new species that was tentatively named Pepper leafroll chlorosis virus (PeLRCV). Using a specific RT-PCR assay for this isolate confirmed the presence of this new viral species in the symptomatic peppers. Aphid transmission experiments showed that PeLRCV is vectored by Aphis gossypii and that it can infect at least five out of the 15 different plants species tested. Based on our findings, PeLRCV is a new member of genus Polerovirus in the family Luteoviridae.

Characterization of lettuce big-vein associated virus and Mirafiori lettuce big-vein virus infecting lettuce in Saudi Arabia.

During 2014 and 2015, 97 lettuce plants that showed big-vein-disease-like symptoms and seven weed plants were collected from the Riyadh region. DAS-ELISA revealed that 25% and 9% of the lettuce plants were singly infected with LBVaV and MiLBVV, respectively, whereas 63% had a mixed infection with both viruses. The results were confirmed by multiplex reverse transcription polymerase chain reaction using primers specific for LBVaV and MiLBVV. LBVaV and MiLBVV were also detected in Sonchus oleraceus and Eruca sativa, respectively. The nucleotide sequence of LBVaV and MiLBVV Saudi isolates ranged from 94.3-100%, and their similarities to isolates with sequences in the GenBank database ranged from 93.9 to 99.6% and 93.8 to 99.3%, respectively. Olpidium sp. was present in the roots of lettuce plants with big-vein disease and it was shown to facilitate transmission of both viruses.

Evaluation of exposure of pemphigus vulgaris patients to Mycobacterium tuberculosis and Aspergillus fumigatus.

The purpose of this study was to screen pemphigus vulgaris (PV) (autoimmune bullous skin disease) for the presence of immunoglobulin G against Mycobacterium tuberculosis and Aspergillus fumigatus. The sera of 60 PV patients and 28 controls were screened for the presence of immunoglobulin G against M. tuberculosis and A. fumigatus by enzyme-linked immune-sorbent assay. Forty patients were females and 20 were males. The range of IgG against M. tuberculosis was from 0.9 to 152.6 (median = 2.95) in the patients and was from 0 to 2.2 (median = 1.6) in the controls. Seven (11.7 %) patients and none of the controls exceeded the cut-off value. Four patients were on systemic steroids and azathioprine and three did not receive treatment before. The results showed that PV patients had significantly more IgG against M. tuberculosis than the controls; the p value was 0.006. The range of IgG against A. fumigatus was from 1.3 to 76.3 (median = 4.9) in the patients and was from 1 to 105.3 (median = 5.25) in the controls. Six (10 %) patients and eight (28.6 %) controls exceeded the cut-off value. The six patients were on systemic steroids and azathioprine. No significant difference was detected between PV patients and controls regarding exposure to A. fumigatus; the p value was 0.308. PV patients showed significantly more exposure to the M. tuberculosis than the controls. This suggests that M. tuberculosis may contribute to the pathogenesis of PV.

Changes in temporomandibular joint morphology in class II patients treated with fixed mandibular repositioning and evaluated through 3D imaging: a systematic review.

To estimate the effects of skeletal class II malocclusion treatment using fixed mandibular repositioning appliances on the position and morphology of the temporomandibular joint (TMJ). Two independent reviewers performed comprehensive electronic searches of MEDLINE, EMBASE, EBM reviews and Scopus (until May 5, 2015). The references of the identified articles were also manually searched. All studies investigating morphological changes of the TMJ articular disc, condyle and glenoid fossa with 3D imaging following non-surgical fixed mandibular repositioning appliances in growing individuals with class II malocclusions were included in the analysis. Of the 269 articles initially reviewed, only 12 articles used magnetic resonance imaging and two articles used computed tomography (CT) or cone-beam CT images. Treatment effect on condyle and glenoid fossa was discussed in eight articles. Treatment effect on TMJ articular disc position and morphology was discussed in seven articles. All articles showed a high risk of bias due to deficient methodology: inadequate consideration of confounding variables, blinding of image assessment, selection or absence of control group and outcome measurement. Reported changes in osseous remodelling, condylar and disc position were contradictory. The selected articles failed to establish conclusive evidence of the exact nature of TMJ tissue response to fixed mandibular repositioning appliances.

Thermoluminescence properties of lithium magnesium borate glasses system doped with dysprosium oxide.

We report the impact of dysprosium (Dy(3+)) dopant and magnesium oxide (MgO) modifier on the thermoluminescent properties of lithium borate (LB) glass via two procedures. The thermoluminescence (TL) glow curves reveal a single prominent peak at 190 °C for 0.5 mol% of Dy(3+). An increase in MgO contents by 10 mol% enhances the TL intensity by a factor of 1.5 times without causing any shift in the maximum temperature. This enhancement is attributed to the occurrence of extra electron traps created via magnesium and the energy transfer to trivalent Dy(3+) ions. Good linearity in the range of 0.01-4 Gy with a linear correlation coefficient of 0.998, fading as low as 21% over a period of 3 months, excellent reproducibility without oven annealing and tissue equivalent effective atomic numbers ~8.71 are achieved. The trap parameters, including geometric factor (µg), activation energy (E) and frequency factor (s) associated with LMB:Dy are also determined. These favorable TL characteristics of prepared glasses may contribute towards the development of Li2O-MgO-B2O3 radiation dosimeters.

Intraoperative and delayed wound approximation in closure of skin defects in different areas.

OBJECTIVE: Wound approximation device is an interesting reconstructive option but not well popularised. In this study we present a simple device that can be used for immediate or delayed closure of large dermal wounds in different anatomical areas. METHOD: Patients with acute and chronic wounds were recruited and underwent immediate intra-operative wound approximation and/or delayed wound approximation, with a home-made wound approximation device. RESULTS: Approximation time in the immediate closure group ranged from 20-140 minutes. Satisfactory scars were obtained in 19 patients (76%) and adherent scars developed in 6 patients. Delayed wound approximation was used successfully in closure of 9 defects. CONCLUSION: This simple dermal wound approximation device can be used intraoperatively to successfully close large difficult wounds, located on the trunk and thigh, with minimal complications. The device can also be used to approximate delayed wounds located in regions where closure is particularly problematic, like the lower leg, foot, and scalp. Some modifications of the device are needed to improve its safety and efficacy. Wound tension is detrimental to adequate wound healing and tensile strength, another basic principle that should not be overlooked to avoid wound dehiscence. Wound approximation is adding to reconstructive options, not replacing them, and they must always be considered.

First Report of Watermelon chlorotic stunt virus Infecting Watermelon in Saudi Arabia.

In the Saudi Arabian deserts, watermelon [Citrullus lanatus (Thunb.)] is cultivated in the lowlands and wadis (washes) where water accumulates following rainfall, and where heat, salt, and drought stress are common constraints on production. During the spring of 2014, watermelon leaves exhibited yellowing and severe chlorotic mottling symptoms. The foliar symptoms were reminiscent of Watermelon chlorotic stunt virus (WmCSV), a bipartite begomovirus previously reported in several neighboring countries (1,3). Ten samples were collected from three farms in the Leith region, where 100% of the watermelon plants were symptomatic. Total nucleic acids were extracted from the symptomatic watermelon plants and were subjected to PCR using WmCSV DNA-A specific primers designed based on a complete genome sequence (GenBank Accession No. AJ012081), WmCSVF-3'-CGTGCTGTTGCCCCCACTGT-5' and WmCSVR-3'-CCTGCATATCTCGTGCCAGAATC-5' to obtain an expected size fragment of 1,111 bp located between the nucleotide (nt) coordinates 400-1510. The amplicons (one per sample) were cloned, and the DNA sequence was determined for each and used to search the NCBI database. The top hits for sequences obtained from all 10 samples were to WmSCV sequences, with shared nt identity values of 97 to 98%. To clone the full-length begomoviral DNA-A and DNA-B components, nucleic acids were subjected to rolling circle amplification (RCA) (2). The RCA products were cloned into the pGEM7 plasmid vector using the unique restriction sites, identified as HindIII for DNA-A, and as EcoRI for DNA-B, respectively. Ten DNA-A clones and two DNA-B component clones were sequenced. The DNA-A components ranged in size from 2,751 (KM066100) to 2,752 bp (KJ939448), whereas the DNA-B components were 2,757 bp in size (KJ939447). Analysis of the viral sequences from the DNA-A clones indicated they had the characteristics of a typical genome of a begomovirus DNA-A component that consist of a hairpin stem-loop structure in the intergenic region, two tandem copies of the iteron (TGGAGAC) located between the nt coordinates 2675 and 2680, 2682 and 2688 predicted to be involved in Rep binding, and six predicted genes encoding proteins with high sequence identity to those encoded by other WmCSV isolates. The 10 DNA-A component sequences were aligned with sequences for previously described WmCSV isolates available in GenBank using Muscle, followed by pairwise comparisons using SDT software (4). The analysis revealed that the cloned DNA-A components shared 99 to 100% nt sequence identity with each other, and 97 to 98% nt identity with WmCSV isolates reported from Yemen (AJ012081), Jordan (EU561237), Iran (AJ245652), and Sudan (AJ245650). Further, the WmCSV DNA-B from Saudi Arabia shared the highest nt identity with sequences from Yemen (AJ012082) at 96%, Iran (AJ245653) at 95%, and only 94% with DNA-B from both Sudan (AJ245651) and Jordan (EU561236). To our knowledge, this is the first report of WmCSV in Saudi Arabia. WmCSV poses a serious threat to the production of this highly valued crop in Saudi Arabia and considerably reduces crop yield (1). References: (1) I. D. Bedford et al. Eur. J. Plant Pathol. 100:243, 1994. (2) A. Idris et al. Plant Dis. 97:910, 2007. (3) A. Kheyr-Pour et al. Phytopathology 90:629, 2000. (4) B. Muhire et al. Arch. Virol. 158:1411, 2013.

First Report of Tomato spotted wilt virus in Lettuce Crops in Saudi Arabia.

A survey for viruses in open field lettuce crops was carried out in March 2014 in the Al-Uyaynah area, central region of Saudi Arabia. In one plot, more than 50% of the lettuce plants (Lactuca sativa; hybrid: Romaine), with the majority of the affected plants in the edges of the plot, were showing virus-like symptoms such as necrotic lesions, necrosis of the lamina of the younger leaves, and leaf curling, indicating a possible infection by a Tospovirus, possibly Tomato spotted wilt virus (TSWV). Most of them were dead when the field was visited again 3 weeks later. Samples from 10 symptomatic and two asymptomatic plants were collected. Five of the samples from symptomatic and two from asymptomatic plants were mechanically inoculated onto Nicotiana benthamiana and N. glutinosa (three indicator plants of each species were used for each sample) using 0.1 M phosphate buffer (pH 7) containing 0.01M Na2SO3 mM. All the symptomatic lettuce samples were also tested serologically using polyclonal antisera (3) against TSWV, CMV, and by using monoclonal antibodies against potyviruses. Moreover, total RNA was extracted (1) and detection of TSWV was also attempted with reverse transcription (RT)-PCR using species specific primers (4) for a 276-bp fragment of the L RNA segment. In both serological and molecular methods, positive and negative controls were included. All the mechanically inoculated plants with tissue from the symptomatic lettuce plants of N. benthamiana showed chlorotic local lesions followed by systemic top necrosis 2 to 3 weeks post inoculation. Similarly, all inoculated N. glutinosa plants showed necrotic local lesions followed by systemic chlorosis. However, all the indicator plants mechanically inoculated with tissue from asymptomatic lettuce plants gave no reaction. All the symptomatic lettuce samples reacted positively, while asymptomatic samples reacted negatively in ELISA tests with TSWV antiserum and the presence of the virus was further confirmed by RT-PCR by using specific primers (method A) (4). PCR products of two randomly selected positive samples were directly sequenced and BLAST analysis of the obtained sequences (Accession Nos. KJ701035 and KJ701036) revealed 99% nucleotide and 100% amino acid identity with the deposit sequence in NCBI from South Korea (KC261947). Regarding mechanical inoculation, 10 days post-inoculation, both indicator plants showed typical symptoms of TSWV infection, such as necrotic local lesions, systemic necrotic patterns, and leaf deformation. None of the symptomatic plants was found to be infected with either CMV or potyvirus. To our knowledge, this is the first report of TSWV naturally infecting lettuce in Saudi Arabia; therefore, insect vector and weed management are necessary measures to control the virus spread to other crops such as tomato and pepper (2). References: (1) E. Chatzinasiou et al. J. Virol. Meth. 169:305, 2010. (2) E. K. Chatzivassiliou. Plant Dis. 92:1012, 2008. (3) E. K. Chatzivassiliou et al. Phytoparasitica 28:257, 2000. (4) R. A. Mumford et al. J. Virol. Meth. 46:303, 1994.

First Report of Tomato chlorosis virus (ToCV) in Tomato Crops in Saudi Arabia.

During January 2014, open field and greenhouse tomato (Solanum lycopersicum L.) crops in the peripheral areas of Riyadh region (Al-Aflaj, Al-Kharj, Al-Waseel, and Al-Dalam), Saudi Arabia, were surveyed. In all surveyed tomato crops, yellowing symptoms were observed on the lower leaves, possibly infected by a whitefly transmitted crinivirus (family Closteroviridae) such as Tomato chlorosis virus (ToCV) and/or Tomato infectious chlorosis virus (TICV). Dense population of whiteflies (Bemisia tabaci G.) were present in all affected plants. Incidence of the yellowing disease varied between four greenhouses and three open field tomato crops, but in the majority of the tomato crops surveyed, symptoms typical of Begomovirus infection such as severe stunting, degeneration, upward cupping, distortion and interveinal yellowing of upper leaves, and flower abortion were also observed. Tomato yellow leaf curl virus (TYLCV) is endemic in Saudi Arabia causing severe crop losses (1). Twenty-six leaf samples from 24 symptomatic and two asymptomatic plants from four fields (three greenhouses and one open field crop) were collected and were processed in the lab at King Saud University. Whitefly transmission on tomato indicator plants was carried out using B. tabaci to fulfill Koch's postulates. Two hundred virus-free B. tabaci adults were confined to one of the collected symptomatic tomato sample singly infected with ToCV for a 48-h acquisition access period, followed by a 48-h inoculation access period on five healthy tomato plants Hybrid Super Strain B, using 40 whiteflies per plant. Crinivirus detection following transmission was conducted by RT-PCR. Total RNA was extracted from 26 collected leaf samples using the Total RNA Purification Kit and analyzed by SCRIPT One-Step RT-PCR Kit (Jena Bioscience). First, the degenerate primers HS-11/HS12 were used for amplification of a 587-bp fragment of the HSP70 gene of ToCV and TICV (3). Second, the RT-PCR product was subjected to a nested PCR using specific primers TIC-3/TIC-4 and TOC-5/TOC-6, for the detection of both TICV and ToCV, respectively (2). Finally, degenerate primers (AV494/AC1048) were used for detection of begomoviruses (4). No fragment was amplified by TIC-3/TIC-4 primer whereas TOC-5/TOC-6 amplified a size of 463 bp in all 24 symptomatic tested samples, including one mixed infection with TYLCV detected by AV494/AC1048. Asymptomatic samples did not produce any amplicon regarding TICV, ToCV, and Begomovirus detection. The amplicons of four positive fragments, each from one field, were further sequenced in both directions and all obtained sequences (KJ433488, KJ433489, KJ433490, and KJ433491) analyzed with BLAST and revealed 99% identity with the most closely deposited sequences in NCBI from Japan (AB513442) and Brazil (JQ952601). In the transmission tests, ToCV was detected to all tomato indicator plants which revealed yellowing symptoms 6 weeks post inoculation, whereas no transmission was obtained when non-viruliferous whitefly adults fed on two asymptomatic tomato leaves. To our knowledge, this is the first report of ToCV infecting tomato crops in Saudi Arabia. Further studies are being carried out to study epidemiology and genetic diversity of this virus associated with yellowing diseases of tomato in different regions of Saudi Arabia. This finding is important for the tomato crops and possibly other virus hosts as may cause serious epidemics and crop losses. References: (1) A. M. Ajlan et al. Arab J. Biotech. 10:179, 2007. (3) C. I. Dovas et al. Plant Dis. 86:1345, 2002. (2) J. Navas-Castillo et al. Plant Dis. 84:835, 2000. (4) S. D. Whyatt and J. K. Brown. Phytopathology 86:1288, 1996.

Does nonlinear blood-brain barrier transport matter for (lower) morphine dosing strategies?

Morphine blood-brain barrier (BBB) transport is governed by passive diffusion, active efflux and saturable active influx. This may result in nonlinear plasma concentration-dependent brain extracellular fluid (brainECF) pharmacokinetics of morphine. In this study, we aim to evaluate the impact of nonlinear BBB transport on brainECF pharmacokinetics of morphine and its metabolites for different dosing strategies using a physiologically based pharmacokinetic simulation study. We extended the human physiologically based pharmacokinetic LeiCNS-PK3.0, model with equations for nonlinear BBB transport of morphine. Simulations for brainECF pharmacokinetics were performed for various dosing strategies: intravenous (IV), oral immediate (IR) and extended release (ER) with dose range of 0.25-150 mg and dosing frequencies of 1-6 times daily. The impact of nonlinear BBB transport on morphine CNS pharmacokinetics was evaluated by quantifying (i) the relative brainECF to plasma exposure (AUCu,brainECF/AUCu,plasma) and (ii) the impact on the peak-to-trough ratio (PTR) of concentration-time profiles in brainECF and plasma. We found that the relative morphine exposure and PTRs are dose dependent for the evaluated dose range. The highest relative morphine exposure value of 1.4 was found for once daily 0.25 mg ER and lowest of 0.1 for 6-daily 150 mg IV dosing. At lower doses the PTRs were smaller and increased with increasing dose and stabilized at higher doses independent of dosing frequency. Relative peak concentrations of morphine in relation to its metabolites changed with increasing dose. We conclude that nonlinearity of morphine BBB transport affects the relative brainECF exposure and the fluctuation of morphine and its metabolites mainly at lower dosing regimens.

Effects of lifestyle physical activity and sedentary behaviour interventions on disease activity and patient- and clinician- important health outcomes in rheumatoid arthritis: a systematic review with meta-analysis.

BACKGROUND: Lifestyle physical activity (PA) is defined as any type of PA undertaken as part of daily life. It can include engagement in activities of daily living (i.e., household chores, gardening, walking to work), incidental PA, walking and/or reducing sedentary or sitting behaviours (SB). Regular PA is recommended for people with Rheumatoid Arthritis (RA) to reduce disease activity and systemic inflammation, as well as to improve patient- and clinician-important health outcomes. However, there is no summarised evidence of the effectiveness of interventions specifically targeting lifestyle PA and SB in this population. The aims of this systematic review with meta-analysis were to evaluate interventions targeting lifestyle PA and/or SB on 1) disease activity; 2) PA, SB and 3) patient- and clinician-important outcomes in people with RA. METHODS: Eight databases [Medline, Cochrane Library CENTRAL, Web of Science, PsychINFO, Cumulative Index to Nursing & Allied Health Literature, Scopus, Excerpta Medica database and Physiotherapy Evidence Database] were searched from inception-August 2022. Inclusion criteria required interventions to target lifestyle PA and/or SB, conducted in adults with RA, assessing patient- and/or clinician-important outcomes. RESULTS: Of 880 relevant articles, 16 interventions met the inclusion criteria. Meta-analyses showed statistically significant effects of interventions on disease activity (standardised mean difference = -0.12 (95% confidence interval = -0.23 to -0.01, I2 = 6%, z = 2.19, p = .03), moderate-to-vigorous PA, light/leisure PA, steps, functional ability, and fatigue. Whereas, no intervention effects were visualised for total PA, pain, anxiety or quality of life. CONCLUSIONS: Lifestyle PA interventions led to increased PA, reductions in SB and improvements in disease activity and other patient- and/or clinician-important health outcomes in people with RA. Future interventions should be less heterogenous in content, structure, focus and outcome measures used to aid understanding of the most effective intervention components for improving health. More SB interventions are needed to determine their effectiveness at producing clinical benefits.

Acral lesions of vitiligo: why are they resistant to photochemotherapy?

BACKGROUND: Acral lesions of vitiligo are usually resistant to conventional lines of treatment as well as surgical interventions. OBJECTIVE: To clarify causes underlying resistance of acral lesions to pigmentation in vitiligo by studying some of the factors associated with mechanisms of repigmentation following photochemotherapy. METHODS: The study included twenty patients with active vitiligo. Skin biopsies were taken from lesional and perilesional skin of areas expected to respond (trunk and proximal limb) and skin of acral areas, before and after PUVA therapy. Sections were stained with H and E, Melan-A, MHCII, CD1a, SCF and c-kit protein. RESULTS: Before treatment acral areas showed significantly lower hair follicle density, melanocyte density, Langerhans cell (LC) density, epidermal MHCII expression, lesional SCF expression and perilesional c-kit expression. Following treatment with PUVA in both non-responsive acral and repigmenting non-acral lesions identical immunohistochemical changes in the form of significant decrease in LC density, epidermal MHC-II and SCF expression were observed. CONCLUSION: The surprisingly similar histochemical changes in response to PUVA in acral and non-acral lesions did not manifest with clinical repigmentation except in non-acral ones. Factors such as inherent lower melanocyte density, lower melanocyte stem cell reservoirs and/or lower baseline epidermal stem cell factor may be considered as possible play makers in this respect.

Resistance to low-dose aspirin therapy among patients with acute coronary syndrome in relation to associated risk factors.

BACKGROUND: A substantial proportion of patients have recurrence of vascular events despite daily intake of low-dose aspirin therapy. Therefore, different patients may require different aspirin dosages to achieve complete inhibition of platelet function. OBJECTIVE: The aim of this work was to measure the response to low-dose aspirin therapy (150 mg/day) among patients with unstable angina or non-ST-segment elevation myocardial infarction and to find out whether titrating aspirin dosage to 300 mg/day, would provide a better therapeutic response in the resistant cases. Moreover, we also aimed to study any association between aspirin non-responsiveness and atherothrombotic risk factors. METHODS: The antiplatelet effect of 150 mg/day aspirin was studied prospectively in 50 consecutive patients with unstable angina or non-ST-segment elevation myocardial infarction. Platelet aggregation was measured using optical platelet aggregometry and serum thromboxane B(2) level. Aspirin resistance was defined as collagen (1 µg/mL) and adenosine diphosphate (ADP) (5 µmol/L)-induced platelet aggregation of ≥ 40% when compared with control values. Twenty healthy age- and sex-matched individuals were taken as a control group. All patients were subjected to complete medical history (risk factors, medications), thorough clinical examination, ECG, coronary angiography and laboratory investigations including: complete haemogram, coagulation, kidney, liver and lipid profiles, fasting blood glucose and glycated haemoglobin (HbA(1C) ). RESULTS: Eleven of 50 patients (22%) were found to be aspirin resistant. A highly significant difference was found between the mean values of ADP, collagen-induced platelet aggregation percentage and thromboxane B(2) level after aspirin 150 mg/day when compared with the corresponding mean values after aspirin 300 mg/day among the resistant patients (66 ± 7.01%, 62 ± 4.34% and 620 ± 64.58 pg/mL, respectively, vs. 26.87 ± 2.85%, 16.5 ± 3.8% and 77 ± 11.3 pg/mL) indicating enhanced response to aspirin after escalating the dose. The presence of atherothrombotic risk factors (hypertension, smoking, family history of ischaemic heart disease and previous MI) were not statistically different between aspirin-resistant and aspirin-sensitive patients. However, there was a highly significant difference between the aspirin sensitive and the resistant patients regarding the other risk factors (diabetes mellitus and dyslipidaemia) (P < 0.01). CONCLUSION: There is inter-individual variability in response to the antiplatelet effect of standard doses of aspirin (150, 300 mg/day). The response to aspirin 300 mg/day is enhanced in resistant patients when compared to 150 mg/day. There was a significant association between aspirin resistance and atherothrombotic risk factors (diabetes, hyperlipidaemia and obesity).

Role of oxidative stress in angiogenesis and the therapeutic potential of antioxidants in breast cancer.

The escalation of cancer cases globally, especially breast cancer, is of concern. Angiogenesis is hallmark of cancer pathogenesis and plays an important role in cancer progression and metastasis. Pro-angiogenic agents, secreted by tumor cells, form new blood vessels, and produce reactive oxygen species (ROS). ROS promote angiogenesis via two major pathways: namely Vascular Endothelial Growth Factor (VEGF) dependent and non-VEGF dependent pathways. As a consequence of unbalanced ROS overproduction and low antioxidants levels, oxidative stress occurs and promotes angiogenesis in breast cancer tissues. Thus, the potential use of antioxidants as a preventive therapy in breast cancer. Preclinical studies depict that vitamins A and E may counter oxidative stress resulting in reduction of metastasis and viability of breast cancer. Furthermore, clinical studies demonstrate a decline in breast cancer risk in postmenopausal women upon the consumption of antioxidants. Herein, we discuss various pro-angiogenic agents that may play an important role in breast cancer angiogenesis. Moreover, the contribution of oxidative stress in inducing the angiogenic process is extensively reviewed here. Furthermore, the findings of pre-clinical and clinical studies on the use of antioxidants, namely vitamins A and E, in breast cancer are deliberated upon, along with the role of angiogenesis in cancer therapy.

Management of Maxillofacial Gunshot Injuries With Emphasis on Damage Control Surgery During the Yemen Civil War. Review of 173 Victims From a Level 1 Trauma Hospital in Najran, Kingdom of Saudi Arabia.

Study Design: Studies on the concept of Damage Control Surgery (DCS) in the management of firearm injuries to the oral and maxillofacial region are still scarce, hence the basis for the current study. Objectives: The objectives of the current study is to share our experience in the management of maxillofacial gunshot injuries with emphasis on DCS and early definitive surgery. Methods: This was a retrospective study of combatant Yemeni patients with maxillofacial injuries who were transferred across the border from Yemen to Najran, Kingdom of Saudi Arabia. Demographics and etiology of injuries were stored. Paths of entry and exit of the projectiles were also noted. Also recorded were types of gunshot injury and treatment protocols adopted. Data was stored and analyzed using IBM SPSS Statistics for Windows Version 25 (Armonk, NY: IBM Corp). Results: A total of 408 victims, all males, were seen during the study period with 173 (42.4%) males sustaining gunshot injuries to the maxillofacial region. Their ages ranged from 21 to 56 years with mean ± SD (27.5 ± 7.6) years. One hundred and twenty-one (70.0%) victims had extraoral bullet entry, while 53 (30.0%) victims had intraoral entry route. Ocular injuries, consisting of 25 (14.5%) cases of ruptured globe and 6 (3.5%) cases of corneal injuries, were the most commonly associated injuries. A total of 78 (45.1%) hemodynamically unstable victims had DCS as the adopted treatment protocol while early definitive surgery was carried out in 47(27.2%) hemodynamically stable victims. ORIF was the treatment modality used for the fractures in 132 (76.3%) of the victims. Conclusions: We observed that 42.4% of the war victims sustained gunshot injuries. DCS with ORIF was the main treatment protocol adopted in the management of the hemodynamically unstable patients.

Endothelin receptor A-specific stimulation of glomerular inflammation and injury in a streptozotocin-induced rat model of diabetes.

AIMS/HYPOTHESIS: Activation of endothelin receptor-A (ET(A)) increases glomerular permeability to albumin (P(alb)) and elevates pro-inflammatory markers in hyperglycaemic rats. METHODS: Male Sprague-Dawley rats were given streptozotocin (n = 32) or saline (sham; n = 32). Half of the animals in each group received the ET(A)-selective antagonist, ABT-627 (atrasentan; orally), beginning immediately after hyperglycaemia was confirmed. Glomeruli were isolated by sieving techniques and P(alb) determined from the change in glomerular volume induced by oncotic gradients of albumin. Glomerular nephrin levels were assessed by immunofluorescence, whereas urinary nephrin was measured by immunoassay. RESULTS: At 3 and 6 weeks after streptozotocin injection, proteinuria was significantly increased compared with sham controls and significantly reduced by ABT-627 treatment. P(alb) was also increased at 3 and 6 weeks post-streptozotocin. ABT-627 had no effect on P(alb) or protein excretion in sham control rats. In glomeruli isolated from hyperglycaemic rats, incubation with BQ-123, a selective ET(A) antagonist, reduced P(alb), whereas BQ-788, a selective endothelin receptor-B antagonist had no effect (n = 6 rats per group, 5-8 glomeruli per rat). Glomerular and plasma content of soluble intercellular adhesion molecule-1 and monocyte chemoattractant protein-1 were significantly increased 6 weeks after streptozotocin (ELISA). ABT-627 attenuated these increases. After 6 weeks of hyperglycaemia, glomerular nephrin content was decreased with a concurrent increase in urinary nephrin excretion. ABT-627 prevented glomerular nephrin loss in hyperglycaemic rats (n = 5-8 rats per group; eight groups). CONCLUSIONS/INTERPRETATION: These observations support the hypothesis that endothelin-1, via the ET(A) receptor, directly increases P(alb), possibly via nephrin loss, as well as early inflammation in the hyperglycaemic rat.

Polychlorobornane components of toxaphene: structure-toxicity relations and metabolic reductive dechlorination.

2,2,5-endo,6-exo,8,9,10-Heptachlorobornane and four derivatives of this heptachlorobornane, with an additional chlorine atom at position 3-exo,8,9, or 10, account for a major portion of the acute toxicity of toxaphene and for up to 23 percent of toxaphene composition as analyzed by open tubular column gas-liquid chromatography with an electron capture detector. Both in several organisms and model environmental systems and on photolysis, this heptachlorobornane undergoes facile reductive dechlorination at the geminal-dichloro group and sometimes dehydrochlorination.

Toxaphene, a complex mixture of polychloroterpenes and a major insecticide, is mutagenic.

Toxaphene, the most widely used chlorinated insecticide, is mutagenic in the Salmonella test without requiring liver homogenate for activity. This insecticide is a complex mixture (more than 177 polychloroterpenes) with carcinogenic activity in rodents. Some but not all of the mutagenic components are easily separated from the insecticidal ingredients.

Minimal genomic variability in Merremia mosaic virus isolates endemic in Merremia spp and cultivated tomato in Puerto Rico.

Merremia mosaic virus (MerMV), a bipartite begomovirus, was identified for the first time as a pathogen of commercial tomato plantings. Infection of tomato by MerMV caused mild leaf curling and yellow foliar mosaic symptoms. Herein, the MerMV was identified in symptomatic Merremia quinquefolia and M. aegyptia (Convolvulaceae) plants exhibiting bright yellow or yellow-green foliar mosaic symptoms, respectively. The full-length begomoviral components were amplified from total DNA isolated from two wild species of Merremia and commercial tomato plants during 1991-1998. The DNA was subjected to rolling circle amplification, restriction digestion, and DNA sequencing. The resultant 19 and 26 apparently full-length DNA-A and DNA-B components were ~ 2557 and ~ 2492 bases, respectively. The 140-base common region was 97.9% identical between DNA-A and -B components, a predictive evidence for cognate DNA-A and -B components. Although the DNA-A components were highly conserved at 96-100%, the DNA-B components diverged at ~ 89 to 100%, respectively. The overall clonal genomic features strongly suggested that MerMV lineage has been under host-selection for some time, and only recently, has undergone a host-shift, putatively, from wild convolvulaceous species to tomato (Solanaceae). Phylogenetically, MerMV grouped with other bipartite begomoviruses indigenous to the Caribbean region, with MerMV DNA-A components forming three clusters, and the DNA-B components grouped in one clade. Both clades contained only one closet relative, an isolate of MerMV from Venezuela, MerMV-VE. Biolistic inoculation of M. quinquefolia and tomato seedlings with the DNA-A and -B components of PR68 and PR80 resulted in development of symptoms like those observed in naturally-infected species, respectively.

Sleep-Disordered Breathing Is Associated with Reduced Mandibular Cortical Width in Children.

INTRODUCTION: Evidence from the adult population suggests that sleep-disordered breathing (SDB) (i.e., obstructive sleep apnea [OSA]) is negatively associated with bone mineral density. Whether a similar association exists in children with SDB has not been investigated. Using the mandibular cortical width (MCW) as a proxy for skeletal bone density, we investigated if children at risk of SDB or diagnosed with OSA have a reduced mandibular cortical width compared to children without SDB. METHODS: Two retrospective cross-sectional studies were performed. The first study included comparison of MCW between 24 children with polysomnographically (PSG) diagnosed OSA and 72 age- and sex-matched control children. The second study included a cohort of children in which SDB was suggested by the Pediatric Sleep Questionnaire (PSQ) ( n = 101). MCW was measured from panoramic radiographs. RESULTS: Multiple-predictors regression analysis from the first study indicated that in children with a severe form of SDB, as induced by OSA severity, there was a negative association with MCW (ß = -0.290, P = 0.049). Moreover, PSG-diagnosed OSA children had thinner MCW (2.9. ± 0.6mm) compared to healthy children (3.5 ± 0.6 mm; P = 0.002). These findings were further supported by the second study illustrating that PSQ total scores were negatively associated with MCW (ß = -0.391, P < 0.001). CONCLUSIONS: Findings suggest that children at risk for or diagnosed with SDB exhibit reduced mandibular cortical width that purportedly may reflect alterations in bone homeostasis. KNOWLEDGE TRANSFER STATEMENT: We report that sleep-disordered breathing (including its severe form, obstructive sleep apnea) in children is associated with reduced mandibular cortical width. This association might be a direct consequence of reduced bone health to sleep-disordered breathing or a reflection that reduced bone formation underlies the development of sleep-disordered breathing. Our findings suggest that mandibular cortical width can be used as an adjunct diagnostic parameter for the diagnosis of sleep-disordered breathing.