Linum usitatissimum seeds oil down-regulates mRNA expression for the steroidogenic acute regulatory protein and Cyp11A1 genes, ameliorating letrezole-induced polycystic ovarian syndrome in a rat model.

The safety and effectiveness of nutricetics suggest that they may offer an alternative to pharmaceutical and surgical therapy for hormone-dependent disorders, such as polycystic ovarian syndrome (PCOS). We investigated the effects of Linum usitatissimum seed oil (LSO) on ovarian functionality, its molecular targets, and the oxidative response in hyperandrogenism-induced polycystic ovary. The composition of LSO has been analyzed using ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS). A well-established PCOS rat model orally administered with letrozole daily for 21 days was used to investigate the effect of LSO at doses of 1 and 2 mL/kg body weight for 28 days. The effect on hormonal profile and antioxidant status, histopathology (cell proliferation), and the expression ratio of the steroidogenic acute regulatory protein (StAR) and Cyp11A1 gene were evaluated. LSO exerted beneficial effects on PCOS rat models via restoring glutathione (GSH), malondialdehyde (MDA), beta subunit subunit luteinizing hormone (LH), testosterone levels, and histopathological scoring. Furthermore, LSO reversed the elevated StAR and Cyp11A1 genes in the PCOS rat model. This study demonstrated the molecular and cellular mechanisms of the beneficial effect of LSO against the reproductive and metabolic disorders of PCOS.

Pre-Transplant Marital Status and Hematopoietic Cell Transplantation Outcomes

Background: Evidence about the impact of marital status before hematopoietic cell transplantation (hct) on outcomes after hct is conflicting. Methods: We identified patients 40 years of age and older within the Center for International Blood and Marrow Transplant Research registry who underwent hct between January 2008 and December 2015. Marital status before hct was declared as one of: married or living with a partner, single (never married), separated or divorced, and widowed. We performed a multivariable analysis to determine the association of marital status with outcomes after hct. Results: We identified 10,226 allogeneic and 5714 autologous hct cases with, respectively, a median follow-up of 37 months (range: 1-102 months) and 40 months (range: 1-106 months). No association between marital status and overall survival was observed in either the allogeneic (p = 0.58) or autologous (p = 0.17) setting. However, marital status was associated with grades 2-4 acute graft-versus-host disease (gvhd), p < 0.001, and chronic gvhd, p = 0.04. The risk of grades 2-4 acute gvhd was increased in separated compared with married patients [hazard ratio (hr): 1.13; 95% confidence interval (ci): 1.03 to 1.24], and single patients had a reduced risk of grades 2-4 acute gvhd (hr: 0.87; 95% ci: 0.77 to 0.98). The risk of chronic gvhd was lower in widowed compared with married patients (hr: 0.82; 95% ci: 0.67 to 0.99). Conclusions: Overall survival after hct is not influenced by marital status, but associations were evident between marital status and grades 2-4 acute and chronic gvhd. To better appreciate the effects of marital status and social support, future research should consider using validated scales to measure social support and patient and caregiver reports of caregiver commitment, and to assess health-related quality of life together with health care utilization.

The American Society of Pediatric Hematology/Oncology workforce assessment: Part 2-Implications for fellowship training.

The American Society of Pediatric Hematology/Oncology (ASPHO) solicited information from division directors and fellowship training program directors to capture pediatric hematology/oncology (PHO) specific workforce data of 6 years (2010-2015), in response to an increase in graduating fellows during that time. Observations included a stable number of physicians and advanced practice providers (APPs) in clinical PHO, an increased proportion of APPs hired compared to physicians, and an increase in training-level first career positions. Rapid changes in the models of PHO care have significant implications to current and future trainees and require continued analysis to understand the evolving discipline of PHO.

Laparoscopic and open inguinal hernia repair: Patient reported outcomes in the elderly from a single centre - A prospective cohort study.

BACKGROUND: With those over 65 making up over 16% of the UK's population, surgeons are counselling increasing numbers of elderly patients for hernia repair. Data is currently lacking comparing different repair methods of inguinal hernias in the elderly population with regards to patient reported outcomes. AIM: To compare open and laparoscopic hernia repair in patients >65 years old and those <65 years old with respect to patient reported outcomes. METHOD: As part of a quality assurance process patients receive a telephone consultation day 2 post procedure. This includes an optional survey with questions to quantify pain, general feeling, nausea, dizziness, drowsiness, satisfaction and vomiting since the operation. Patients were then classified into age ≥ 65 years or <65 years and subclassified into totally extraperitoneal (TEP) or open inguinal hernia repair (IHR). RESULTS: Data is presented from patients treated between January 2009 and August 2016, totalling those included 1167 of 2522 (55.5%). Only five patients (4.42%) reported moderate pain; in the >65 TEP group this was significantly lower (10.2% open IHR <65; 6.7% TEP <65; 12.8% open IHR >65). Patient satisfaction with the surgery was satisfied or very satisfied in all patients in all groups. CONCLUSION: Time off work is not an absolute appropriate measure of return to premorbid status with respect to the elderly as a substantial number of >65 year olds have retired. We therefore present this interesting insight into patient perceptions following hernia repair by age group. Overall patients over 65 can expect the same high levels of satisfaction and low levels of pain following either technique for inguinal hernia repair as younger patients.

Cytokeratin 13, Cytokeratin 17, and Ki-67 Expression in Human Acquired Cholesteatoma and Their Correlation With Its Destructive Capacity.

OBJECTIVES: Cholesteatoma is a nonneoplastic destructive lesion of the temporal bone with debated pathogenesis and bone resorptive mechanism. Both molecular and cellular events chiefly master its activity. Continued research is necessary to clarify factors related to its aggressiveness. We aimed to investigate the expression of Ki-67, cytokeratin 13 (CK13) and cytokeratin 17 (CK17) in acquired nonrecurrent human cholesteatoma and correlate them with its bone destructive capacity. METHODS: A prospective quantitative immunohistochemical study was carried out using fresh acquired cholesteatoma tissues (n=19), collected during cholesteatoma surgery. Deep meatal skin tissues from the same patients were used as control (n=8). Cholesteatoma patients were divided into 2 groups and compared (invasive and noninvasive) according to a grading score for bone resorption based upon clinical, radiologic and intraoperative findings. To our knowledge, the role of CK17 in cholesteatoma aggressiveness was first investigated in this paper. RESULTS: Both Ki-67 and CK17 were significantly overexpressed in cholesteatoma than control tissues (P<0.001 for both Ki-67 and CK17). In addition, Ki-67 and CK17 were significantly higher in the invasive group than noninvasive group of cholesteatoma (P=0.029, P=0.033, respectively). Furthermore, Ki-67 and CK17 showed a moderate positive correlation with bone erosion scores (r=0.547, P=0.015 and r=0.588, P=0.008, respectively). In terms of CK13, no significant difference was found between cholesteatoma and skin (P=0.766). CONCLUSION: Both Ki-67 and CK17 were overexpressed in cholesteatoma tissue and positively correlated with bone resorption activity. The concept that Ki-67 can be a predictor for aggressiveness of cholesteatoma was supported. In addition, this is the first study demonstrating CK17 as a favoring marker in the aggressiveness of acquired cholesteatoma.

Pathogenesis and Bone Resorption in Acquired Cholesteatoma: Current Knowledge and Future Prospectives.

Cholesteatoma is a cystic non tumorous lesion of the temporal bone that has the ability to destroy nearby structures by its power to cause bone resorption and as a result, fatal complications prevail. We aimed to conduct a comprehensive review for pathogenesis of acquired cholesteatoma, bone resorption mechanisms, and offer a future vision of this serious disease. We have reviewed different theories for pathogenesis of acquired cholesteatoma including the most relevant and updated ones with special emphasis on the mechanisms of bone resorption through Medline/PubMed research using the keywords 'aetiopathogenesis, bone resorption, acquired cholesteatoma, temporal bone, and cytokines.' In order to strengthen our study, we searched the reference lists of identified reviews. Cholesteatoma is a subject of debate among otolaryngologists since it was prescribed firstly. Over many decades, several theories were postulated for aetiopathogenesis of cholesteatoma with a tendency to follow more than one theory to explain the proper nature of that disease. Until now, the mechanism of bone resorption has yet to be more clarified. In the last century, a leap has occurred in the field of biomolecular cholesteatoma research which improved our knowledge about its pathophysiology and bone destructive mechanism. However, surgery is still the only available treatment. We conclude that discovery of new therapeutic choices for cholesteatoma other than surgery by the use of anti-growth, anti-proliferative, apoptotic agents as well as medications that antagonize osteoclastogenesis should be the main concern in the future clinical and experimental research work. Also, searching for predictors of the aggressiveness of cholesteatoma can affect the timing of intervention and prevent occurrence of complications.

Aspergillus thyroiditis: first antemortem case diagnosed by fine-needle aspiration culture in a pediatric stem cell transplant patient.

Aspergillus thyroiditis (AT) has historically been considered a postmortem diagnosis in immunocompromised patients; most have disseminated disease. This report summarizes the clinical challenge of diagnosing AT. It also highlights the value of the early use of thyroid fine-needle aspiration culture and the need for a high index of suspicion to reach the final diagnosis before disease dissemination.

The effect of magnesium sulphate infusion on the incidence and severity of emergence agitation in children undergoing adenotonsillectomy using sevoflurane anaesthesia.

This randomised, controlled, double-blind study investigated the effects of intra-operative magnesium sulphate administration on the incidence of emergence agitation in children undergoing adenotonsillectomy using sevoflurane anaesthesia. Seventy children were randomly allocated to receive a 30 mg.kg(-1) bolus of intravenous magnesium sulphate after induction of anaesthesia followed by a continuous infusion of 10 mg.kg(-1).h(-1) or an equal volume of saline 0.9%. All children received titrated sevoflurane anaesthesia adjusted to maintain haemodynamic stability. The Pediatric Anesthesia Emergence Delirium scale and the Children's Hospital of Eastern Ontario Score were used for the assessment of postoperative emergence agitation and pain, respectively. Emergence agitation was more common in the control group than in the magnesium group (23 (72%) and 12 (36%), respectively (p = 0.004)), with a relative risk of 0.51 (95% CI 0.31-0.84), an absolute risk reduction of 0.35 (95% CI 0.10-0.54), and number needed to treat of 3 (95% CI 2-9). Postoperative pain scores were comparable in the two groups. Magnesium sulphate reduces the incidence and severity of emergence agitation in children undergoing adenotonsillectomy using sevoflurane anaesthesia and is not associated with increased postoperative side-effects or delayed recovery.

Assessment of musculoskeletal function and mood in haemophilia A adolescents: a cross-sectional study.

Haemophilia A is characterized by the occurrence of frequent spontaneous intra-articular and intramuscular bleeding. If inadequately treated, it results in progressive damage to joints and muscles leading to crippling deformities and musculoskeletal dysfunction. These complications result in lifelong chronic pain and disability that may greatly affect the patients' mood. We aimed to evaluate the musculoskeletal function in our haemophilia A patients and its correlation to depressed mood in these patients and determine the impact of degree of factor VIII deficiency, different replacement therapy regimens and frequency of hemarthrosis, on both musculoskeletal function and mood. A cross-sectional study was carried out on 50 adolescent haemophilia A patients. Musculoskeletal function was assessed using Functional Independence Score for Hemophilia (FISH) and mood status was assessed using Beck Depression Inventory-Short Form (BDI-SF). The mean FISH score was 23.32 ± 4.69 (range 13-28) and the tasks that obtained lower scores were step climbing, squatting and walking. Of our 50 patients included, 16(32%) were not depressed, 18(36%) were with mild depression, 11(22%) were with moderate depression and 5(10%) were with severe depression. There was a highly significant negative correlation between mean FISH score and mean BDI-SF score (P < 0.001). The better the replacement therapy regimen, the better the musculoskeletal function that could be obtained in haemophilia A patients and the better the mood.

Degradation pathways of a corticotropin-releasing factor antagonist in solution and solid states.

Stability of the 1,3,5-triazine derivative (1), a corticotropin-releasing factor inhibitor, was studied in acidic solutions and in solid formulations. Degradant structures were elucidated using liquid chromatography/mass spectrometry (LC/MS) and nuclear magnetic resonance (NMR). Compound 1 was found to undergo hydrolysis via two pathways. Pathway 1 involves three hydrolysis steps of the triazine ring. Pathway 2 proceeds through hydroxy substitution of the amino group on the triazine ring followed by its hydrolysis, eventually resulting in the formation of the same degradant as pathway 1. Stability of 1 in the tablets was dependent on the manufacturing process and degradation appeared to proceed more rapidly in amorphous regions created during processing. Pathways 1 and 2 were observed in the tablets and degradation rate was enhanced at high humidity condition. In addition to pathways 1 and 2, degradation in the tablet formulations was found to proceed through a third pathway involving nucleophilic displacement of the ether methoxy group by the triazine N-3. The resulting imidazolidinium intermediate was found to undergo a series of hydrolytic steps finally leading to the same end degradant as pathways 1 and 2. This intermediate was observed at a lower concentration in the tablet at the high humidity conditions and at very low concentrations in acidic solutions.

The postoperative histologic changes in the nasal mucosa following treatment with amoxycilline or rifampicin: preliminary findings.

This study examines the postoperative histologic changes in the nasal mucosa following treatment with amoxycilline or rifampicin. Three groups of nasal mucosal biopsies were obtained from 20 patients having undergone nasal surgery (partial middle turbinectomy). The first group was obtained immediately before surgery (control group). The second and third groups were taken postoperatively (after the first and 6 weeks of amoxycilline or rifampicin therapy, 10 patients each). The histologic changes in the nasal mucosa and the density of seromucinous glands were examined using histochemical methods and image analyzer. Amoxycilline treatment was associated with squamous metaplasia and a statistically significant reduction in the percent area of the seromucinous glands compared to the control group (p < 0.05). Rifampicin therapy was associated with minimal reduction in the density of the seromucinous glands and absence of metaplastic changes. In nasal surgeries, rifampicin but not amoxycilline had a beneficial effect on postoperative nasal mucosa status.

NIR chemical imaging to guide/support BMS-561389 tablet formulation development.

The objective of this study was to determine whether the particle size of extra-granular tartaric acid affects the uniformity of its distribution within BMS-561389 tablets. A near-infrared imaging technique was used to assess the distribution of tartaric acid near the surface of tablet tops and bottoms. Three batches of BMS-561389 tablets were manufactured using three lots of granular tartaric acid having different particle size distributions. Near-Infrared chemical images were acquired on the tops and bottoms of 15 tablets from each lot. Spectra were collected from 1350 to 1600 nm in 10 nm increments and 16 co-added scans at each wavelength. Data were analyzed using ISys 3.1 (Spectral Dimensions, Inc.) Chemical Imaging Software. Data analysis consisted of preprocessing, principal component analysis, and image analysis of the principal component scores image. It was feasible to map tartaric acid particles near the surface of BMS-561389 tablets using near infrared chemical imaging. The tartaric acid particle size statistics based on image analysis results correlated well with pre-compaction measurements using a laser-light scattering method. The image analysis results indicate that segregation of tartaric acid between tablet tops and bottoms was apparent in tablets lots containing both the largest and intermediate-size tartaric acid particles. For tablets made with the smallest tartaric acid particles, differences between tablet tops and bottoms in either the number of tartaric acid particles or the percent tablet surface area covered by tartaric acid were not statistically different at the 95% confidence level.

The role of genetic susceptibility in head and neck squamous cell carcinoma.

Our research is an additional genetic study to uncover the molecular mechanisms involved in head and neck squamous cell carcinoma (HNSCC) pathogenesis by studying loss of heterozygosity (LOH) and microsatellite instability (MSI) in both premalignant and malignant patients and to highlight the genotype of HNSCC in Upper Egypt. Patients with HNSCC from various parts of the world may have unique genotypes and this is the first genetic study of HNSCC in Sohag 500 KM to the south of Cairo. We performed a prospective study of 41 patients with precancerous and 79 patients with cancerous laryngeal, esophageal, nasopharyngeal, nasal and oral lesions, and 50 controls (The control patients were cases admitted for ear surgery or simple nasal surgery, from whom we took biopsy from mucosal lining of nasopharynx). The present study included 170 individuals who were admitted to the Ear, Nose and Throat department, Sohag University Hospital, Sohag, in Egypt in the period between April 2001 and March 2003. Samples which were taken by punch biopsy were frozen and stored at -80 degrees C and were subjected to histopathological examination. We investigated LOH and MSI by using six microsatellite markers located at chromosomes 3, 5, 9, and 17. The markers used were D3S1286, D9S171, D9S753, D17S654, D17S695, and CFS1-R. LOH was in all premalignant and malignant lesions at 5q33.3-q34 and 13% of Controls. LOH at 17p21 was absent in all premalignant lesions and was found in 53% of malignant lesions and 12.4% of Controls. In premalignant lesions, LOH was at 3pter-3p24.2 (73% of cases), at 9p21 (46%), at 9q21.1-22.3 (37%), and at 17p13 (37%). These percents increased in malignant lesions to 87, 80, 67, and 63%, respectively. They were 14, 19.4, 17, and 19% in controls. Examination of LOH could improve diagnosis, adds additional confidence, in HNSCC by DNA extraction from suspicious lesions in high-risk groups (smokers and alcoholics) and LOH at 3p/9p seems to be of particular value for early detection and definition of progression risk. If there are high percent of LOH at these chromosomes, active intervention should be done (chemoprevention and regular follow up head and neck examination for very early detection and management).

Soil solid-phase controls lead activity in soil solution.

Lead pollution of the environment is synonymous with civilization. It has no known biological function, and is naturally present in soil, but its presence in food crops is deemed undesirable. The concern regarding Pb is mostly due to chronic human and animal health effects, rather then phytotoxicity. However, not much is known about the chemistry and speciation of Pb in soils. We determined the activity of Pb2+, in near neutral and alkaline soils, representative of alluvial, desertic and calcareous soils of Egypt, using the competitive chelation method. Lead activity ranged from 10(-6.73) to 10(-4.83) M, and was negatively correlated with soil and soil solution pH (R2 = -0.92, P < 0.01 and R2 = -0.89, P < 0.01, respectively). It could be predicted in soil solution from the equation: log(Pb2+) = 9.9 - 2pH. A solubility diagram for the various Pb minerals found in soil was constructed using published thermodynamic data obtained from the literature, and our measured Pb2+ activities compared with this information. The measured Pb2+ activities were undersaturated with regard to the solubility of PbSiO3 in equilibrium with SiO2 (soil). However, they were supersaturated with regard to the solubilities of the Pb carbonate minerals PbCO3 (cerussite) and Pb3(CO3)2(OH)2 in equilibrium with atmospheric CO2 and hydroxide Pb(OH)2. They were also supersaturated with regard to the solubilities of the Pb phosphate minerals Pb3(PO4)2, Pb5(PO4)3OH, and Pb4O(PO4)2 in equilibrium with tricalcium phosphate and CaCO3. The activity of Pb2+ was not regulated by any mineral of known solubility in our soils, but possibly by a mixture of Pb carbonate and phosphate minerals.

Screening for amyloid in subcutaneous fat tissue of Egyptian patients with rheumatoid arthritis: clinical and laboratory characteristics.

OBJECTIVE: To screen for amyloid and to assess associated clinical and laboratory characteristics in Egyptian patients with rheumatoid arthritis (RA). METHODS: Abdominal subcutaneous fat aspirates were consecutively collected from 112 patients (103 women, nine men) having RA for five years or more. To detect amyloid, fat smears were stained with Congo red and the concentration of amyloid A protein in fat tissue was measured. Clinical, radiological, and laboratory characteristics of the patients were assessed. RESULTS: Amyloid was detected in eight (7%) of the fat smears stained with Congo red. Compared with the Congo red stain, the sensitivity for detecting amyloid by measurement of amyloid A protein in fat tissue was 75% and the specificity was 100%. The amount of amyloid found was small for both methods. The median disease duration of the eight amyloid patients was significantly longer (17 years) than that of the non-amyloid patients (10 years). Bronchopulmonary disease and constipation were more common, whereas proteinuria and chronic renal insufficiency were not. The number of swollen joints and the number of red blood cells were significantly lower in the amyloid group. CONCLUSIONS: Quantification of amyloid A protein and staining with Congo red are strongly concordant methods of screening for amyloid in fat tissue. The prevalence of amyloid in Egyptian patients with RA is 7%. Proteinuria is not a discriminating feature, whereas long disease duration, constipation, bronchopulmonary symptoms, and a moderate to low number of red blood cells may help to identify the arthritic patients with amyloid.

Cadmium content of wheat grain from a long-term field experiment with sewage sludge.

Grain Cd concentrations were determined in the wheat (Triticum aestivum L.) cultivars Soissons, Brigadier, and Hereward grown in 1994,1996, and 1999, respectively, in soils of a long-term field experiment to which sewage sludges contaminated with Zn, Cu, Ni, or Cr had previously been added. Soil pore water soluble Cd and free Cd2+ increased linearly with increasing total soil Cd (R2=0.82 and 0.84, respectively; P<0.001). Similarly, soil pore water free Cd2+ increased linearly with increasing soil pore water soluble Cd (R2=0.98; P<0.001). There was no evidence of a plateau in soil pore water Cd concentrations with increasing soil Cd concentrations. Grain Cd concentrations were significantly correlated with total soil Cd (P<0.001), soil pore water Cd (P<0.001), and free Cd2+ (P<0.001). A slight curvilinear relationship between grain Cd and soil Cd was apparent, but there was no plateau, even at the maximum soil Cd concentration of about 2.7 mg kg(-1). The relationship between soil pore water Cd and grain Cd was linear for all three cultivars. The slopes were in the order 1994 > 1996 > 1999, with more Cd being taken up into the grain by Soissons grown in 1994, and least by Hereward grown in 1999. For Soissons, Cd concentration in the grain greater than the EU limit (0.24 mg kg(-1) dry wt.) occurred at soil Cd less than the current UK limit of 3 mg kg(-1) for soils receiving sewage sludge. In contrast, for Brigadier and Hereward, grain Cd concentrations were near to and less than the EU limit, respectively, at soil Cd concentrations of 3 mg kg(-1).