Genome-wide DNase I-hypersensitive site assay reveals distinct genomic distributions and functional features of open chromatin in autopolyploid sugarcane.

The characterization of cis-regulatory DNA elements (CREs) is essential for deciphering the regulation of gene expression in eukaryotes. Although there have been endeavors to identify CREs in plants, the properties of CREs in polyploid genomes are still largely unknown. Here, we conducted the genome-wide identification of DNase I-hypersensitive sites (DHSs) in leaf and stem tissues of the auto-octoploid species Saccharum officinarum. We revealed that DHSs showed highly similar distributions in the genomes of these two S. officinarum tissues. Notably, we observed that approximately 74% of DHSs were located in distal intergenic regions, suggesting considerable differences in the abundance of distal CREs between S. officinarum and other plants. Leaf- and stem-dependent transcriptional regulatory networks were also developed by mining the binding motifs of transcription factors (TFs) from tissue-specific DHSs. Four TEOSINTE BRANCHED 1, CYCLOIDEA, and PCF1 (TCP) TFs (TCP2, TCP4, TCP7, and TCP14) and two ethylene-responsive factors (ERFs) (ERF109 and ERF03) showed strong causal connections with short binding distances from each other, pointing to their possible roles in the regulatory networks of leaf and stem development. Through functional validation in transiently transgenic protoplasts, we isolate a set of tissue-specific promoters. Overall, the DHS maps presented here offer a global view of the potential transcriptional regulatory elements in polyploid sugarcane and can be expected to serve as a valuable resource for both transcriptional network elucidation and genome editing in sugarcane breeding.

H3K27 demethylase SsJMJ4 negatively regulates drought-stress responses in sugarcane.

Sugarcane (Saccharum spp.), a leading sugar and energy crop, is seriously impacted by drought stress. However, the molecular mechanisms underlying sugarcane drought resistance, especially the functions of epigenetic regulators, remain elusive. Here, we show that a S. spontaneum KDM4/JHDM3 group JmjC protein, SsJMJ4, negatively regulates drought-stress responses through its H3K27me3 demethylase activity. Ectopic overexpression of SsJMJ4 in Arabidopsis reduced drought resistance possibly by promoting expression of AtWRKY54 and AtWRKY70, encoding two negative regulators of drought stress. SsJMJ4 directly bound to AtWRKY54 and AtWRKY70, and reduced H3K27me3 levels at these loci to ensure their proper transcription under normal conditions. Drought stress down-regulated both transcription and protein abundance of SsJMJ4, which was correlated with the reduced occupancy of SsJMJ4 at AtWRKY54 and AtWRKY70 chromatin, increased H3K27me3 levels at these loci, as well as reduced transcription levels of these genes. In S. spontaneum, drought stress-repressed transcription of SsWRKY122, an ortholog of AtWRKY54 and AtWRKY70, was associated with increased H3K27me3 levels at these loci. Transient overexpression of SsJMJ4 in S. spontaneum protoplasts raised transcription of SsWRKY122, paralleled with reduced H3K27me3 levels at its loci. These results suggest that the SsJMJ4-mediated dynamic deposition of H3K27me3 is required for an appropriate response to drought stress.

Antibacterial and Anticandidal Activity of the Nanostructural Composite of a Spirothiazolidine-Derivative Assembled on Silver Nanoparticles.

Our aims in this work are the preparation of an ionic liquid based on heterocyclic compounds with Ag nanoparticles and the investigation of its application as an antibacterial and anticandidal agent. These goals were achieved through the fabrication of an ionic liquid based on Ag nanoparticles with 5-Amino-3-(4-fluorophenyl)-N-hexadecyl-7-(4-methylphenyl)-2-H spiro[cyclohexane1,2'-[1,3]thiazolo [4,5-b]pyridine]-6-carbonitrile (P16). The nanostructure of the prepared ionic liquid was characterized using techniques such as FTIR, 1HNMR, 13CNMR, UV, SEM, and TEM. The biological activity of the prepared compound (P16) and its nanocomposites with Ag nanoparticles was tested using five clinical bacteria (Pseudomonas aeruginosa 249; Escherichia coli 141; Enterobacter cloacae 235; Staphylococcus epidermidis BC 161, and methicillin-resistant S. aureus 217), and three Candida species (Candida utilis ATCC 9255; C. tropicalis ATCC 1362, and C. albicans ATCC 20402). The FTIR, 1HNMR, and 13CNMR results confirmed the chemical structure of the synthesized P16 compound. The nanostructure of the prepared ionic liquid was determined based on data obtained from the UV, SEM, and TEM tests. The antibacterial and anticandidal results showed that the biological activity of the compound (P16) was enhanced after the formation of nanocomposite structures with Ag nanoparticles. Moreover, the biological activity of the compound itself (P16) and that of its nanocomposite structure with Ag nanoparticles was higher than that of ampicillin and amphotericin B, which were used as control drugs in this work.

Dynamic physiological and transcriptomic changes reveal memory effects of salt stress in maize.

BACKGROUND: Pre-exposing plants to abiotic stresses can induce stress memory, which is crucial for adapting to subsequent stress exposure. Although numerous genes involved in salt stress response have been identified, the understanding of memory responses to salt stress remains limited. RESULTS: In this study, we conducted physiological and transcriptional assays on maize plants subjected to recurrent salt stress to characterize salt stress memory. During the second exposure to salt stress, the plants exhibited enhanced salt resistance, as evidenced by increased proline content and higher POD and SOD activity, along with decreased MDA content, indicative of physiological memory behavior. Transcriptional analysis revealed fewer differentially expressed genes and variations in response processes during the second exposure compared to the first, indicative of transcriptional memory behavior. A total of 2,213 salt stress memory genes (SMGs) were identified and categorized into four response patterns. The most prominent group of SMGs consisted of genes with elevated expression during the first exposure to salt stress but reduced expression after recurrent exposure to salt stress, or vice versa ([+ / -] or [- / +]), indicating that a revised response is a crucial process in plant stress memory. Furthermore, nine transcription factors (TFs) (WRKY40, WRKY46, WRKY53, WRKY18, WRKY33, WRKY70, MYB15, KNAT7, and WRKY54) were identified as crucial factors related to salt stress memory. These TFs regulate over 53% of SMGs, underscoring their potential significance in salt stress memory. CONCLUSIONS: Our study demonstrates that maize can develop salt stress memory, and the genes identified here will aid in the genetic improvement of maize and other crops.

A Systematic Investigation on the Influence of Intumescent Flame Retardants on the Properties of Ethylene Vinyl Acetate (EVA)/Liner Low Density Polyethylene (LLDPE) Blends.

Because of their high filler loadings, commercial-grade clean flame-retardant materials have unstable mechanical properties. To address this issue, intumescent polymers can be used to develop clean flame retardants with very low levels of smoke and toxicity generation. An intumescent flame retardant (IFR) system composed of red phosphorus (RP), zinc borate (ZB), and a terpolymer of ethylene, butyl acrylate, and maleic anhydride (EBM) was used to prepare EVA (ethylene-vinyl acetate) and EVA/LLDPE (linear low-density polyethylene) composites; their mechanical and flammability properties were systematically investigated. The limiting oxygen index (LOI) of the EVA/LLDPE (as base material) composite containing RP and ZB mixed with nonhalogenated flame retardant, mainly magnesium hydroxide (MH) and coadditives, including processing aids and thermal stabilizers, was established. RP was found to have little effect on the tensile properties of EVA/LLDPE 118W/120 phr flame-retardant (MH + RP) composites. There was a minute difference in the effective trend of RP between tensile strength and elongation at break. Following the addition of ZB, the elongation at break of the composites gradually decreased with increasing RP content and then leveled off when the RP content was over 10 phr. Mechanical properties (elongation at break and tensile strength) can be best maintained at below 10 phr content of RP. The mechanical properties decreased with lower amounts of EBM content. In addition, flame retardancy increased when the EBM content decreased. The findings further revealed that MH and RP have poor compatibility, yielding poor mechanical properties. The LOI greatly increased with RP content, even though the total content of flame retardants (main + intumescent flame retardant) was the same in all formulations. Only over 5 phr RP content formulations passed V-0 of the UL-94 test. When under 5 phr, the RP content formulations did not pass V-0 of the UL-94 test.

Strategies towards Producing Non-Polar Dolomite Nanoparticles as Nanofiller for Copolymer Nanocomposite.

Poly (ethylene-co-vinyl acetate) (PEVAc) is a copolymer endowed with high elasticity and resilient properties, potentially utilized in various applications. However, the tensile strength of this copolymer is insufficient for use in certain applications that require enough strength to tolerate high external tension or stress. In this study, dolomite was proposed as a nanofiller to reinforce the PEVAc. Raw dolomite was physically and chemically modified in order to improve its mix ability and interfacial adhesion between the PEVAc and dolomite. Initially, the size of dolomite was reduced by combining the ball-milling and tip-sonication methods. SEM, TEM, and XRD were used to characterize the morphology/structure of the raw dolomite and the size-reduced dolomite. Then, a particle size analysis was performed to confirm the average particle size. Our results show that the particle size of dolomite was reduced from 150 µm to 441.4 nm by the physical modification process (size reduction). Based on the TEM analysis, the Feret diameter (df) of the dolomite particles was also reduced from ~112.78 µm to ~139.58 nm only. This physically modified dolomite is referred as dolomite nanoparticles (DNPs), since one or more of its dimensions is less than 100 nm (e.g., thickness and width). To further improve the dolomite and PEVAc matrix interactions, chemical modification of the DNPs were performed by treating the DNPs with stearic acid, forming non-polar dolomite nanoparticles (NP-DNPs). The presence of stearic acid in dolomite was confirmed through FTIR and contact angle analyses. A PEVAc nanocomposite film with NP-NPDs as a nanofiller appeared more homogeneous and exhibited the highest increment in tensile strength and elongation at break. These findings indicated that the combination of ball milling and tip sonication is an efficient method for producing very fine dolomite particles up to the nano-size range, whereas chemical surface modifications improved the compatibility between the dolomite and the copolymer. The combination of these physical and chemical modifications helped to develop a homogeneous copolymer nanocomposite system with improved tensile properties.

Facile approaches for determination of Bromhexine Hydrochloride and its active metabolite Ambroxol Hydrochloride using Eosin Y.

New validated Spectroscopic methods were developed to assay Bromhexine Hydrochloride and its active metabolite Ambroxol Hydrochloride separately in pure form and pharmaceutical formulations. The spectrophotometric assay (method I) shows complex formation between each of the drugs and Eosin Y at 540nm at pH 3.6 and 3.4mL of 4×10-4M Eosin for Bromhexine and Ambroxol. The Spectrofluorimetric assay (method II) depends on quenching eosin native fluorescence by the studied drugs, which measured at 540nm after excitation at 302nm. The spectrophotometric absorbance-concentration plot is rectilinear over the ranges (1.0-5.0) and (1.0-10.0) µg/mL for bromhexine and ambroxol with LOD of 0.31 and 0.14µg/mL and LOQ of 0.94 and 0.42µg/mL for the two drugs respectively. The fluorometric-concentration plot is linear along the range (1.0-5.0) µg/mL and (1-10) µg/mL for the two drugs respectively with LOD of 0.13µg/mL and 0.22µg/mL and LOQ of 0.4µg/mL and 0.65µg/mL for the two drugs, respectively. Developed assays have been validated in agreement with ICH recommendations and they were used in the analysis of commercial drug formulations containing the two mucolytic drugs and the results were matching with those obtained by the comparison method.

Disentangling trait, occasion-specific, and accumulated situational effects of psychological distress in adulthood: evidence from the 1958 and 1970 British birth cohorts.

BACKGROUND: The trajectories of psychological distress differ between individuals, but these differences can be difficult to understand because the measures contain both consistent and situational features; however, in longitudinal studies these sources of information can be disentangled. In addition to occasion-specific features, interindividual differences can be decomposed into two sources of information: trait and carry-over effects between neighboring occasions that are not related to the trait (i.e. accumulated situational effects). METHODS: To disentangle these three sources of variance throughout adulthood, the consistency (trait and accumulated situational effects) and occasion specificity of nine indicators of psychological distress from the Malaise Inventory were examined in two birth cohorts, the 1958 National Child Development Study (NCDS58), and the 1970 British Cohort Study (BCS70). RESULTS: The scale was administered at ages 23, 33, 42, and 50 in NCDS58 (n = 7147), and at ages 26, 30, 34, and 42 in BCS70 (n = 6859). For each psychological symptom, more variance was consistent than occasion-specific. The majority of the consistency was due to trait variance as opposed to accumulated situational effects, indicating that an individual predisposed to be distressed at the beginning of the study remained more likely to be distressed over the whole period. Symptoms of rage were notably more consistent among males than females in both cohorts (78.1% and 81.3% variance explained by trait in NCDS58 and BCS70, respectively), and among females in the NCDS58 (69%). CONCLUSIONS: Symptoms of psychological distress exhibited high stability throughout adulthood, especially among men, due mostly to interindividual trait differences.

Multiple organ resection for large paraganglioma a case report.

Paragangliomas represent a group of neuroendocrine tumours which occur in various localizations. Most of them produce catecholamines, and in advanced cases present with typical symptoms and signs such as palpitations, headache and hypertension. The only curative treatment is radical resection. About one-quarter of paragangliomas are malignant, defined by the presence of distant metastases. There are multiple treatment options for unresectable metastatic tumours. They include radionuclid therapy, chemotherapy, and radiotherapy, although none of them are curative. Cytoreductive surgery can also be considered, especially when the goal is to decrease symptoms related to advanced disease. We present a rare case of a large paraganglioma of the left retroperitoneum. Despite radical surgery, early recurrence of the disease was observed.

Correlation of survival length after pancreaticoduodenectomy for pancreatic head adenocarcinoma depending on tumor characteristics detected by means of computed tomography and resection margins status.

Pancreatic carcinoma is an aggressive tumor with a grim prognosis. Accurate staging is essential for indicating surgery in patients with borderline resectable tumors. This paper examines the correlation between pre-operation characteristics of tumors found on CT, infiltration of individual resection margins as confirmed by a pathologist, and the survival of patients with resectable pancreatic head ductal adenocarcinoma. This prospective cohort study involved patients operated on for pancreatic head adenocarcinoma, which was clearly resectable based on the staging CT and intraoperative observation between 2011-2014. Only patients without postoperative complications who underwent adjuvant chemotherapy were analyzed. Seventy-nine patients were assessed, of which 16 (20.3%) had R0 resection and 63 (79.7%) had R1 resection. Patients with R1 results had up to 2.7 times higher risk of death than patients with R0 resection. We found a trend towards shorter survival associated with a closer relationship of the tumor to the superior mesenteric vein/portal vein (SMV/PV) wall in the pre-operation CT examination. Patients with a tumor interface between the vein wall of up to 180 ° circumference had up to 1.97 times higher risk of death than patients without (p=0.131). The results of our work confirmed that in our center, even surgically treated, clearly resectable pancreatic head tumors still have a high occurrence of positive surgical margins (R1 resection) and that tumors with R1 resection had statistically significantly reduced survival compared to R0 resection. A trend for shorter overall survival was found after tumor resection depending on the increasing interface between the tumor and the SMV/PV wall, but this result was not statistically significant.

Reproductive tract development and histomorphometric analysis of testes in neonatal Zaraibi kids raised on milk replacer supplemented with sodium butyrate.

This study aimed to determine the effect of sodium butyrate (SB) on reproductive tract development and histomorphometric analysis of testes in neonatal kids, as well as on their growth, antioxidant status and some blood metabolites. Thirty-six neonatal Zaraibi kids were divided immediately after 4-5 days from birth into three equal groups (12 kids/ each). The first group (G1) received milk replacer (MR) at a rate of 10% of the body weight until the weaning. The second group (G2) received 9.7% MR supplemented with 0.3% SB. The third group (G3) received whole milk and served as a control. The results revealed that there was significant (p < .001) increase in total and daily gain between the G2 and G1 groups, whereas there was no significant change between G2 and G3 groups. Body condition score was slightly increased (p > .05) in G2 compared with G1. Serum total protein and cholesterol levels were significantly decreased in treated groups compared with the G3 group, on reverse globulin and glucose levels had no significant changes. Also, T3 and testosterone concentrations were significantly (p < .0001 & p < .05) higher in G3 and G2 than G1. Antioxidant status was enhanced through decreasing the oxidative marker and increasing antioxidant enzymes activity in G2. Testis parameters in G3 and G2 kids had the highest values, compared with G1. G1 and G2 had thin basement membrane of seminiferous tubules with few Leydig cells and pyknotic germinal epithelium, while G3 showed thick basement membrane, mild wide interstitial spaces with many Leydig cells. The tubular diameter was also significantly larger in the G3 and G2. It could be concluded that MR supplemented with SB can be used as alternative whole milk in suckling goat kids for maintaining reproductive tract and kids' performance through improving the antioxidant status.

Our experience with transanal total mesorectal excision (TaTME) procedures in middle and distal rectal tumors.

INTRODUCTION: Transanal total mesorectal excision (TaTME) is a relatively new approach in surgical treatment of rectal cancer. There are no clear indications when to choose this strategy. It is a technically demanding procedure for the surgeon with a long learning curve, which should also be taken into account in evaluation of this method. The results of both oncological and postoperative complications must be properly evaluated to explore the benefit of TaTME. The aim of this study is to assess the potential benefit of TaTME compared to other alternatives in middle and distal rectal tumors. METHODS: Retrospective evaluation of patients undergoing TaTME procedure performed by one team of surgeons between October 2014 and June 2019. The authors analyzed demographic indicators of the group of patients, tumor characteristics, specimen quality, early postoperative complications and the possibility of stoma reversal. RESULTS: A total of 93 patients underwent TaTME procedure for middle and distal rectal cancer. Mean BMI was 27.6 (4.8). T3 or T4 tumor was found in 73 (78.5%) patients, 68 (73.1%) patients had positive lymph nodes and 12 (12.9%) patients were treated for synchronous metastatic rectal cancer. Neoadjuvant therapy was used in 80 (86%) patients. Conversion to open laparotomy was necessary in one case (1%). Stapled anastomosis was performed in 37 (39.7%) cases, handsewn in 56 (60.2%). A positive circumferential resection margin (CRM) was found in 10 (10.7%) cases. Distal resection margin (DRM) was positive in 3 (3.2%) patients. Pathological analysis showed a complete mesorectum in 18 patients (19.4%), nearly complete in 39 (41.9%) and an incomplete mesorectum in 36 (38.7%). Complications in the first 30 days after primary surgery were observed in 38 (40.8%) patients, mainly for anastomotic leak (19 patients, 20.4%). Reoperation was required in 7 (7.5%) patients. Permanent colostomy had to be performed in 4 (4.3%) cases. No patient died after surgery. CONCLUSION: In a selected group of patients it is possible to perform resection using this approach with acceptable postoperative morbidity and quality of the specimen. We used TaTME procedure in patients expected to have difficult TME due to obesity, size and distal localization of tumor. The incidence of conversion to open surgery was very low. Further studies for long term oncological outcomes are needed.

Knowledge and awareness of brain death among Saudi population.

OBJECTIVE: To examine the knowledge and awareness of brain death among the Saudi population and to identify what is needed to improve awareness in this community. METHODS: We conducted a cross-sectional study across various regions of the Kingdom of Saudi Arabia from July-December 2018. Data was collected from a sample of the general population via a questionnaire, which obtained sociodemographic data and included questions about assessments and guidelines for brain death. We conducted descriptive statistics, as well chi-square tests to compare between groups, with statistical significance considered at p less than or equal 0.05. RESULTS: We recruited 1244 participants with a mean age of 27.17+/-9.84 (female: n=992; 79.7%, male: n=252; 20.3%). Of these, 1208 (97.1%) were Saudi, 444 (35.7%) were married and 800 (64.3%) were single. The majority had a university degree (n=837; 67.3%), 676 (54.3%) were currently students, approximately a third of whom were from health specialties (n=393; 31.6%), and 192 (15.4%) were unemployed. A mean score of knowledge of 5.53+/-2.61 was observed, equivalent to 42%. There was a significant difference in total knowledge score depending on marital status, region, and educational level and specialization. In contrast, there was no significant difference in knowledge depending on gender, age, nationality, or place of work. CONCLUSION: Our results suggest that Saudi Arabians have little to moderate knowledge about brain death. Education and work-based awareness programs about brain death are needed, particularly regarding prevention and causes.

Affective instability across the lifespan in borderline personality disorder - a cross-sectional e-diary study.

OBJECTIVE: Longitudinal and cross-sectional studies suggest that affective instability is inversely related to greater age in borderline personality disorder (BPD). However, existing studies relied on retrospective self-reports of perceived instability. We examined affective instability in everyday life in patients with BPD and healthy controls (HCs) by age in a cross-sectional e-diary study. METHODS: Two hundred and sixty female participants between 14 and 53 years of age (130 patients with BPD and 130 HCs) carried an e-diary over 4 days. The e-diaries emitted a prompting signal in approximately hourly intervals asking participants to rate their current affective state, that is valence (ranging from pleasant to unpleasant) and tense arousal (ranging from calm/relaxed to restless/under tension). RESULTS: Multilevel analyses revealed a significant interaction of age and group predicting affective instability (valence: F(1,255.6)  = 7.59; P < 0.01; tense arousal: F(1,252)  = 6.08; P < 0.01), suggesting that affective instability significantly declines with greater age in patients with BPD. Controlling for the number of comorbid disorders and BPD severity did not change the results, illustrating an inverse relationship between age and affective instability in BPD (significant interaction of age*group for valence: F(1,238.7)  = 5.74; P < 0.02 and tense arousal: F(1,235.2)  = 5.28; P < 0.02). CONCLUSION: Affective instability during daily life declines with greater age in BPD. This decline is irrespective of comorbidity and BPD severity.

Hip preservation surgery for adolescents and young adults with Post-Perthes Sequelae.

BACKGROUND: Impingement ensures a narrow arc of pathologic loading in adolescent hips with sequelae of Perthes Disease. Proper surgical interference when the hip is still in the pre-arthritic stage restores function and protects the young hip from early degenerative changes. METHODS: Osteochondroplasty at the femoral head-neck junction and relative lengthening of the femoral neck by distal transfer of the greater trochanter was performed for 12 adolescents with combined intra-articular/extra-articular impingement due to sequelae of Perthes disease in terms of coxa magna, coxa plana, coxa brevis, with an overriding greater trochanter. The safe surgical hip dislocation approach was performed in all cases. Patients were followed for an average of 24 months. RESULTS: The Harris hip scores improved from an average of 58 preoperatively (range 50 to 69) to 94 postoperatively (range 91 to 97) at latest follow up. The range of hip flexion improved from a preoperative value of 84.2° (range, 60 to 105°) to value of 120.8° (range, 95 to 130°). Changes in hip flexion averaged 28.6° (range, 15 to 45°). Mean internal rotation increased to 26° ± 12°, and abduction to 38° ± 11°. Alpha angle improved to 40° ± 8°. The mean of center-trochanteric distance improved from an average of -18 mm to -1 mm. No osteonecrosis or chondrolysis was noted up to the time of the latest follow up. CONCLUSION: Elimination of narrow arc of pathologic loading due to impingement is the main advantage of the proposed surgical technique. Other advantages include increased abductor lever arm and restoration of hip joint range of motion with normalization of the loading conditions, and hence future development of degenerative arthritis and the anticipated need for a future joint replacement surgery could be prevented or delayed. Femoral head vascularity is well maintained with the proven safety of the presented surgical approach.

Assessment of the Medial Longitudinal Arch in children with Flexible Pes Planus by Plantar Pressure Mapping.

INTRODUCTION: Plantar Pressure mapping was introduced as a new modality for assessment of the height of the medial longitudinal arch of the foot. Therefore, the aim of this study is to correlate the plantar pressure mapping readings of arch index contact force ratio (AICFR) in children with flexible pes planus with radiographic measurements and static plantar footprints in order to determine the reliability of pressure mapping as a modality for the assessment and follow up of the flat foot deformity. PATIENTS AND METHODS: Radiographic measurements, foot prints, and pressure mapping scans were recorded for each foot at initial presentation and at latest follow up in 28 children (56 feet) with flexible pes planus. RESULTS: A positive correlation of pressure mapping results was found with the talo-first metatarsal angle, the calcaneal pitch angle, as well as the footprint scans (P < 0.001). CONCLUSION: This study demonstrated that plantar pressure mapping is a reliable and effective tool in screening, diagnosis, and follow up of children with flexible pes planus.

A FEMALE PATIENT WITH DUPLICATION OF 7p13-pter ASSOCIATED WITH DEL 20p13pter RESULTING FROM MALSEGREGATED PATERNAL 7;20 BALANCED TRANSLOCATION.

Duplication of the short arm of chromosome 7 is a genomic disorder presenting with distinctive facies including hypertelorism, large anterior fontanel, and intellectual disability. A 2½-year-old Egyptian girl was referred because of cleft palate and dysmorphic features. She showed clinical manifestations of duplication of 7p, along with atypical features of corpus callosum hypogenesis and skeletal anomalies. Chromosome analyses revealed unbalanced translocations involving the short arms of chromosomes 7 and 20 due to malsegregation of a paternal balanced translocation 7;20. Fluorescence in situ hybridization analysis (FISH) of the female patient showed partial trisomy 7p and a subtelomeric monosomy 20p. Thus, the karyotype of our patient is 46,XX,der(20) (7pter --> 7p13::20p13 --> 20qter). In this report, we present the clinical phenotype of this patient with duplication of 7p and review the literature.

Micronucleus assay as a biomarker for chromosome malsegregation in young mothers with Down syndrome children.

The aim of the present study is to test the susceptibility of chromosome 21 malsegregation in young mothers of Down syndrome children using combined micronucleus (MN) assay and FISH analysis. The present study included 62 Egyptian young mothers (age < 30 y) who were divided into 22 mothers of DS offspring and 40 age matched controls. All subjects were subjected to chromosomal analysis, micronucleus assay, and FISH analysis. High statistical significant difference was found between mothers of Down syndrome (MDS) and the controls in the MN percentage (P=0.034). Also there was high statistical significant difference between MDS and the controls in the percentage of positive malsegregation (P =0.0001). The specificity of combined MN% with FISH was 90%, while the sensitivity was 63.6%. Combined MN-FISH test is highly specific but moderately sensitive in assessing the risk of having children with DS in young mothers.

Quantifying treatment delays in adolescents and young adults with cancer at McGill University.

BACKGROUND: Since the end of the 1980s, the magnitude of survival prolongation or mortality reduction has not been the same for adolescents and young adults (ayas) with cancer as for their older and younger counterparts. Precise reasons for those observations are unknown, but the differences have been attributed in part to delays in diagnosis and treatment. In 2003 at the Jewish General Hospital, we developed the first Canadian multidisciplinary aya oncology clinic to better serve this unique patient population. The aim of the present study was to develop an approach to quantify diagnosis delays in our aya patients and to study survival in relation to the observed delay. METHODS: In a retrospective chart review, we collected information about delays, treatment efficacy, and obstacles to treatment for patients seen at our aya clinic. RESULTS: From symptom onset, median time to first health care contact was longer for girls and young women (62 days) than for boys and young men (6 days). Median time from symptom onset to treatment was 173 days; time from first health care contact to diagnosis was the largest contributor to that duration. Delays in diagnosis were shorter for patients who initially presented to the emergency room, but compared with patients whose first health contact was of another type, patients presenting to the emergency room were 3 times more likely to die from their disease. CONCLUSIONS: Delays in diagnosis are frequently reported in ayas with cancer, but the duration of the delay was unrelated to survival in our sample. Application of this approach to larger prospective samples is warranted to better understand the relation between treatment delay and survival in ayas-and in other cancer patient groups.

Stability-Indicating Spectrofluorimetric Methods for the Determination of Metolazone and Xipamide in Their Tablets. Application to Content Uniformity Testing.

A highly sensitive, simple and rapid stability-indicating spectrofluorimetric method was developed for the determination of metolazone (MET) and xipamide (XPM) in their tablets. The proposed method is based on the measurement of the native fluorescence of MET in methanol at 437 nm after excitation at 238 nm and XPM in alkaline methanolic solution at 400 nm after excitation at 255 nm. The fluorescence-concentration plots were rectilinear over the range of 2.0- 20.0 ng/mL for MET and 0.2- 2.0 µg/mL for XPM, with lower detection limits (LOD) of 0.35 ng/mL and 0.02 µg/mL and a lower quantification limit (LOQ) of 1.05 ng/mL and 0.07 µg/mL for MET and XPM, respectively. The method was successfully applied to the analysis of MET and XPM in their commercial tablets and the results were in good agreement with those obtained using the official and comparison methods, respectively. Furthermore, content uniformity testing of the studied pharmaceutical tablets was also conducted. The application of the proposed method was extended to stability studies of MET and XPM after exposure to different forced degradation conditions, such as acidic, alkaline, oxidative and photolytic degradation conditions, according to ICH Guidelines. Moreover, the method was utilized to investigate the kinetics of the alkaline, acidic and photolytic degradation of MET. The apparent first-order rate constants and half-life times were calculated. Proposals for the degradation pathways for both MET and XPM were postulated.