N-acetylcysteine protects against cuprizone-induced demyelination: histological and immunohistochemical study.

BACKGROUND: Myelination is a sequential process that is tightly controlled by a number of intrinsic and extrinsic factors. Any central nervous system disease in which the neuronal myelin sheath is damaged is referred to as demyelinating disease. The present work was designed to study the histopathological, ultrastructural and immunohistochemical changes in rat brain, mainly corpus callosum (CC), following oral administration of cuprizone (CPZ), and the role of N-acetylcysteine (NAC) in reducing these changes. MATERIALS AND METHODS: Demyelination was induced by CPZ administration for short (4 weeks) and long (8 weeks) periods. NAC was given concomitantly and sequentially for similar periods. Spontaneous recovery after cessation of CPZ followed by no medication was also investigated. At the end of each experimental period, both cerebral hemispheres were extracted and prepared for light and electron microscopic examination and immuno-histochemical study. RESULTS: The obtained results showed a direct proportion between the duration of CPZ administration and the severity of demyelination. The co-administration of CPZ and NAC, had a fair protective impact that was stronger than the sequential administration of the two drugs. Incomplete spontaneous remyelination was observed after cessation of CPZ, being more evident in short than in long period group, indicating that when CPZ administration is prolonged, remyelination is delayed. CONCLUSIONS: In the light of the above results, it could be concluded that NAC has neuroprotective effects and has the potential to be a novel therapeutic approach for the treatment of demyelinating diseases such as multiple sclerosis; however, treatment should begin as soon as the disease manifests.

Incidence and exposure assessment of aflatoxins and ochratoxin A in Egyptian wheat.

Aflatoxins and ochratoxin A occur frequently in grains and are associated with carcinogenic, and nephrotoxic properties. Therefore, the aim of this study was to determine the level of aflatoxins and ochratoxin A contamination in wheat samples obtained from different Egyptian governorates and to assess the effect of gamma irradiation on AFB1 in spiked wheat samples, as well as to evaluate the estimated daily intake and hazard index. Thirty-six wheat grain samples purchased from different sale points were analyzed by High-Performance Liquid Chromatography. Data revealed that 33.33 % of the wheat grain samples were contaminated by aflatoxin B1, whereas only 16.66 % of the wheat samples were above the maximum limits (2 µg/kg) set by the European Commission. Ochratoxin A was only detected in two wheat grain samples, and the results were considered below the maximum limit (5 µg/kg) set by the European Commission. On studying the effect of gamma irradiation on wheat samples spiked by aflatoxin B1 (20 µg/kg), results revealed that aflatoxin B1 was reduced to 1.22 and 0.94 µg/kg for samples gamma-irradiated at a dose of 10 and 20 KGy respectively. Estimated daily intake of ochratoxin A in wheat samples was found to be higher than that of the tolerable daily intake; however, hazard index values were below one, thus demonstrating no threat to human health.

Effect of replacement of antibiotics with thyme and celery seed mixture on the feed intake and digestion, ruminal fermentation, blood chemistry, and milk lactation of lactating Barki ewes.

The study investigated the effect of in-feed administration of dried thyme leaf and celery seed mixture (at 1 : 1 DM basis) compared with salinomycin ionophore on milk production and milk nutritive value of Barki ewes. Thirty ewes (37.5 ± 1.8 kg), divided into 3 treatment groups, were fed: (1) a complete control diet comprising concentrates and fodder maize (Zea mays L.) at 60 : 40 dry matter basis, (2) the control diet plus 20 g of thyme and celery mixture supplementation and (3) the control diet supplemented with 1 g of salinomycin per ewe daily for 90 days. Inclusion of thyme-celery treatment increased (P < 0.05) weight gain, average daily gain, milk yield, milk component yields, and feed efficiency, without affecting milk composition. In addition, the thyme-celery treatment enhanced (P < 0.05) nutrient intake and digestibility, total ruminal volatile fatty acids, branched chain fatty acids, and acetate proportions and decreased ammonia-N concentration. Thyme-celery treatment increased (P < 0.05) serum glucose, thyroxine, and glutamate-pyruvate transaminase concentrations. It is concluded that the thyme and celery mixture (1 : 1 DM basis) at 20 g per lactating ewe daily can replace the salinomycin ionophore. Enhanced feed utilization and lactational performance as well as milk nutritive value for human consumption were observed with the natural additive mixture supplementation.

New series of fused pyrazolopyridines: Synthesis, molecular modeling, antimicrobial, antiquorum-sensing and antitumor activities.

New series of fused pyrazolopyridines were prepared and assessed for antimicrobial, antiquorum-sensing and antitumor activities. Antimicrobial evaluation toward selected Gram-positive bacteria, Gram-negative bacteria and fungi indicated that 5-phenylpyrazolopyridotriazinone 4a has good and broad-spectrum antimicrobial activity. In addition, 5-(4-chlorophenyl)pyrazolopyridotriazinone 4b and 5-(4-(dimethylamino)phenyl)pyrazolopyridotriazinone 4c exhibited good activity against the selected Gram-positive bacteria and A. fumigatus, whereas 5-amino-4-phenylpyrazolopyridopyrimidine 6a demonstrated good activity against B. cereus and P. aeruginosa. Furthermore, 6-amino-5-imino-4-phenylpyrazolopyridopyrimidine 7a and 6-amino-4-(4-chlorophenyl)-5-iminopyrazolopyridopyrimidine 7b demonstrated promising activity against the tested Gram-negative bacteria and fungi, and moderate activity against Gram-positive bacteria. Antiquorum-sensing screening over C. violaceum illustrated that 4a, 6a and 7a-c have strong activity. In vitro antiproliferative assessment of the new derivatives against HepG2, HCT-116 and MCF-7 cancer cells revealed that 7a is the most active analog against all tested cell lines. Likewise, 3,7-dimethyl-4-phenylpyrazolopyridopyrimidinone 2a and 6-amino-4-(4-chlorophenyl)-5-iminopyrazolopyridopyrimidine 7b manifested strong activity against all examined cell lines. In vivo antitumor testing of 2a, 7a and 7b against EAC cells in mice indicated that 7a has the highest activity. Cytotoxicity toward WI38 and WISH normal cells was also assessed and results assured that all of the investigated analogs have lower cytotoxicity than doxorubicin. DNA-binding affinity and topoisomerase IIß inhibitory activity were evaluated, and results revealed that 5b, 7a and 7b bind strongly to DNA; in addition, 2a, 4a, 7a and 7b manifested higher topoisomerase IIß inhibitory activity than that of doxorubicin. Analogs 5b, 7a and 7b were docked into topoisomerase IIß, and results indicated that 7a and 7b have the highest binding affinity toward topoisomerase IIß. In silico simulation studies referred that most of the new analogs comply with the optimum needs for good oral absorption. Also, computational carcinogenicity evaluation was predicted.

Optimization unit for real-time applications in unbalanced smart distribution networks.

This paper presents a new generic approach for developing a Jacobian matrix for use with the optimization unit in real-time energy management systems (EMS) for unbalanced smart distribution systems. The proposed formulation can replace approximated calculations for real-time optimal power flow in an optimization unit while providing greater accuracy and requiring less computational time, which is critical for real-time EMS. The effectiveness and robustness of the proposed approach have been tested through simulations with different distribution networks. The simulation results demonstrate a significant reduction in the computational time with the new proposed formulation. Moreover, the results demonstrate the scalability of the proposed approach as the reduction in the computational time is more significant for large practical systems. The proposed approach is characterized by evaluating the scalability and low computational time; thus, it can be used by grid operators in real-time energy management applications for large-scale practical distribution systems.

Synthesis, molecular modeling and biological evaluation of new pyrazolo[3,4-b]pyridine analogs as potential antimicrobial, antiquorum-sensing and anticancer agents.

New pyrazolo[3,4-b]pyridine analogs 2-9 were synthesized and subjected to antimicrobial testing toward chosen Gram-negative bacteria, Gram-positive bacteria and fungi. Compound 2 exhibited potent and extended-spectrum antimicrobial activity. Further, 6 and 9c demonstrated remarkable and extended-spectrum antibacterial activity. Antiquorum-sensing activity of the new members was tested over C. violaceum, whereas 9c demonstrated strong efficacy, while 2, 8b and 9b displayed moderate efficacy. In vitro anticancer assay toward HepG2, MCF-7 and Hela cancer cells manifested that 2 and 9c are powerful and extended-spectrum anticancer agents. Additionally, 8a, 8b and 9b showed excellent activity toward the three cancer cells. In vivo anticancer assay over EAC in mice indicated that 2 and 9c have the greatest activity. Moreover, cytotoxicity assay over WISH and W138 normal cells clarified that the checked analogs possess weak cytotoxicity toward the two normal cells. DNA-binding affinity was also tested, whereas 2, 3, 8b, 9b and 9c demonstrated great affinity. Molecular modeling studies revealed that the investigated compounds bind to DNA through intercalation similarly to doxorubicin. In silico studies revealed that the new members are anticipated to show excellent intestinal absorption.

Configuration of the circle of Willis and its two parts among Egyptian: a magnetic resonance angiographic study.

BACKGROUND: We hypothesized that the collateral circulation differs in different ethnic groups. So, the aim of our work was to study variations of the circle of Willis (COW) among Egyptian and to compare our findings with the findings of other nationalities. MATERIALS AND METHODS: One hundred patients were studied using magnetic resonance angiography (3D-TOF-MRA). Frequency and morphologic variations in COW were studied. The diameters of the arteries of the anterior and posterior circle were verified. Finally, the differences among the mean diameters of these arteries regarding age and sex were also studied. RESULTS: Complete, partially complete and incomplete COW were encountered in 28%, 38% and 34% in the studied cases. The incomplete anterior circle was found in 34% (10% isolated incomplete anterior circle and 24% combined incomplete anterior and posterior circles) and the incomplete posterior circle came across in 62% (38% isolated incomplete posterior circle and 24% combined incomplete anterior and posterior circles). Seven anterior circle variations were found. The commonest type was the classical type "a" with a prevalence of 56%, being higher in male (57.1%). The 2nd common type was type "g" (hypoplasia or aplasia of the anterior communicating artery) with a prevalence of 24%, being higher in male (66.7%). Six posterior circle variations were found. The commonest variation was the classic type "a" with a prevalence of 26%, being higher in male (61.5%). Posterior circles types "d, e, h" (18%, 24%, 20%) constituted 62% and were characterised by hypoplasia/absent of the posterior communicating arteries. CONCLUSIONS: The prevalence of complete COW (classic or textbook type) was encountered only 28% of the studied cases. Variations of COW were found to be more common in the posterior circulation (62%). The incomplete anterior circle was found in 34% and it is mostly caused by hypoplasia or aplasia of the anterior communicating artery which was found to be more common compared to the literature.

Design, synthesis, antimicrobial, antiquorum-sensing and antitumor evaluation of new series of pyrazolopyridine derivatives.

New series of pyrazolopyridines 1-15 were synthesized and esteemed for antimicrobial effectiveness against S. aureus, B. cereus, E. coli, P. aeruginosa, C. albicans, A. fumigatus and A. flavus. Analogs 15c and 15d have eminent and broad spectrum antimicrobial activity, while 13a, 15a, 15e and 15f have potent effectiveness on S. aureus and B. cereus. In addition, 12 exhibited excellent effectiveness on E. coli and P. aeruginosa. Compounds 1-15 were also evaluated for antiquorum-sensing efficacy over C. violacium, whereas 11a, 15b, 15e and 15f showed reasonable efficacy. In vitro antitumor testing of the new analogs against HepG2, MCF-7 and Hela cancer cell lines revealed that 1 and 15d have potent and broad spectrum antitumor activity. In addition, 4, 8 and 15f showed prominent effectiveness on the three chosen cancer cell lines. In vivo antitumor assessment toward EAC in mice revealed that compounds 1 and 15d have the highest efficacy. Furthermore, cytotoxicity evaluation against W138 and WISH normal cells indicated that all screened compounds have lower cytotoxicity than doxorubicin over both normal cell lines. The active antimicrobial and antitumor compounds were estimated for DNA-binding affinity. Compounds 1, 15c and 15d exhibited strong affinity, and they were subsequently docked into DNA, where they displayed good interactions with DNA. In silico studies indicated that the new compounds are predicted to exhibit good oral absorption.

New pyrazolopyridine analogs: Synthesis, antimicrobial, antiquorum-sensing and antitumor screening.

New pyrazolopyridine analogs were prepared and tested for antimicrobial efficacy toward Staphylococcus aureus, Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa, Candida albicans, Aspergillus fumigatus and Aspergillus flavus. Results revealed that compound 6 has prominent and broad spectrum antimicrobial activity. Compound 8 showed good antibacterial efficacy over the four tested bacterial strains. In addition, compounds 2-4 displayed interesting efficacy over S. aureus, B. cereus and P. aeruginosa as well as moderate efficacy toward E. coli, C. albicans, A. fumigatus and A. flavus. Furthermore, compounds 9 and 10 exhibited interesting efficacy over P. aeruginosa. Antiquorum-sensing efficacy of the same analogs toward Chromobacterium violaceum was also examined, whereas compounds 3, 4 and 6 displayed acceptable activity. In vitro antitumor assay of the new pyrazolopyridines toward liver (HepG2), breast (MCF-7) and cervix (Hela) cancer cells illustrated that compounds 2 and 5 have the highest antitumor activity over the three cell lines. Moreover, compound 4 exhibited interesting efficacy on all tested cell lines, whereas compound 7 showed good activity on MCF-7 cells. The most active in vitro antitumor analogs, 2, 4, 5 and 7 were assessed for in vivo antitumor efficacy on Ehrlich ascites carcinoma (EAC) cells, whereas compound 5 displayed the highest efficacy. In addition, cytotoxicity testing toward W138 and WISH normal cells revealed that all tested analogs are less cytotoxic than doxorubicin. The new analogs were evaluated for DNA-binding affinity, whereas compounds 2, 4 and 5 displayed the highest affinity. In silico studies concluded that all the new pyrazolopyridines are foreseen to have excellent oral absorption.

The [4†+†4] thermocyclization of 9-anthraldehyde: synthesis, crystal structure, experimental and theoretical UV spectra, natural bonding orbital analysis and prediction of third-order nonlinear optical properties.

The dimer of 9-anthraldehyde, namely heptacyclo[8.6.6.62,9.03,8.011,16.017,22.023,28]octacosa-3,5,7,11,13,15,17(22),18,20,23(28),24,26-dodecaene-1,9-carbaldehyde, C30H20O2, has been synthesized by refluxing an ethanol solution in the presence of M(ClO4)2 and 1,3-diaminopropan-2-ol (M = Co2+ or Cu2+). Its structure has been determined by single-crystal X-ray diffraction, showing it to be a new polymorph, referred to as polymorph II, in the monoclinic space group P21/n. It is compared with the previously reported triclinic modification [Ehrenberg (1968). Acta Cryst. B24, 1123-1125], which is referred to as polymorph I. The asymmetric unit of polymorph II contains two half molecules located on crystallographic centres, while the asymmetric unit of polymorph I includes one half molecule, also located on a crystallographic centre. Time-dependent density functional theory (TD-DFT) at the RB3LYP level using the 6-31G(d,p) basis set was applied. The predicted electronic absorption spectrum is in good agreement with the experimental one. The analysis of the calculated electronic absorption spectrum of polymorph II was carried out in order to assign the observed electronic transitions and to determine their character. A natural bonding orbital (NBO) analysis was executed at the same level to evaluate charge-transfer, intramolecular hydrogen-bonding interactions and hyperconjugative interactions. The third-order nonlinear optical (NLO) properties of the compound were appraised by the ZINDO/sum-over-states method in both static and dynamic states. The orientationally averaged (isotropic) value of γ for the compound is greater than the corresponding value of 4-nitroaniline (pNA).

Characteristics of systemic lupus erythematosus in a sample of the Egyptian population: a retrospective cohort of 1109 patients from a single center.

Introduction Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that can vary among different ethnic and racial groups. Objective The objective of this paper is to study the prevalence of various manifestations of SLE in a sample of the Egyptian population. Patients and methods Information in this study was derived from the medical records of SLE patients who sought medical advice at a private clinic in Cairo from January 1980 to June 2016. Results This study included 1109 SLE patients, of whom 114 (10.3%) were males and 995 were females (89.7%). Mean age of onset was 25.89 ± 10.81 years, while the median of disease duration from the onset of the disease till the last recorded visit was 26 months. The most common cumulative manifestations were arthritis (76.7%), malar rash (48.5%), leukopenia (45.7%), and photosensitivity (45.6%). A total of 33.1% of the patients had nephritis, and neuropsychiatric lupus was present in 6.4% of the patients. Secondary antiphospholipid syndrome was present in 11.5% of the patients. Antinuclear antibody and anti-double-stranded deoxyribonucleic acid were present in 1060/1094 (96.9%) and 842/1062 (79.3%) of the patients, respectively. Antiphospholipid antibodies were present in 266/636 (41.8%) of the patients, anti-Smith in 54/240 (22.5%), anti-SSA/Ro in 61/229 (20.4%), and anti-SSB/La in 32/277 (11.6%) of the patients. Male patients had a statistically higher prevalence of nephritis ( p = 0.01), whereas arthritis and alopecia were statistically higher in females ( p = 0.012 and p = 0.006, respectively). Patients with juvenile onset had a statistically higher prevalence of nephritis and seizures ( p < 0.001 and p = 0.012, respectively). Conclusions Arthritis and malar rash represented the most common clinical manifestations. Male and juvenile-onset patients had a predilection toward a more severe disease. These results are in agreement with many studies conducted in the Middle East and worldwide. On the other hand, major organ involvement was exceptionally low, which is contradictory to several reports from the Middle East and across the globe.

Synthesis, antimicrobial, antiquorum-sensing and antitumor activities of new benzimidazole analogs.

New benzimidazole analogs were prepared and tested for antimicrobial efficacy toward Escherichia coli ATCC 12435, Bacillus cereus UW 85, Staphylococcus aureus ATCC 29213, Candida albicans and Aspergillus fumigatus 293. Results indicated that compound 10 has potent and broad spectrum antimicrobial activity. In addition, 4b and 5c showed eminent antimicrobial efficacy toward B. cereus, S. aureus, C. albicans and A. fumigatus. Furthermore, 12 and 14 demonstrated interesting antifungal activity toward C. albicans. Antiquorum-sensing efficacy of the new compounds toward Chromobacterium violacium ATCC 12472 was also examined. In vitro antitumor screening of the new benzimidazoles toward HepG2, HCT-116 and MCF-7 cancer cell lines demonstrated that 4b and 5b,c are the most potent analogs toward all tested cell lines. The three potent in vitro antitumor analogs were further assessed for in vivo antitumor activity toward EAC in mice, and in vitro cytotoxicity toward W138 normal cell line. Results revealed that 4b has the highest in vivo activity, and that the three tested analogs are less cytotoxic than 5-FU toward W138 normal cell line. The most active antimicrobial and antitumor analogs were examined for DNA-binding affinity, whereas 4b and 5c displayed the highest affinity. The in silico studies illustrated that all of the new benzimidazoles meet the optimal requirements for good oral absorption and bioavailability. Moreover, in silico toxicity assessment has been reported.

Thick cement usage in percutaneous vertebroplasty for malignant vertebral fractures at high risk for cement leakage.

PURPOSE: To assess the feasibility and safety of transpedicular percutaneous vertebroplasty (PVP) using thick bone cement in patients with intractable metastatic vertebral pain and at high risk for cement leakage. METHODS: Unilateral transpedicular PVP using firm bone cement was performed in 77 patients with intractable pain due to vertebral metastases in the thoracolumbar spine, who had one or more relative contraindication to PVP. Primary outcome measures were the severity of pain as assessed on a 100-mm visual analogue scale and daily morphine consumption. Secondary outcome measures were the degree of disability and the incidence of procedure-related adverse outcomes. The outcome measures were assessed at the preoperative visit and at 1 day, 1 week, 4 weeks and 12 weeks after the procedure. RESULTS: Sixty-three (81.8%) patients completed the 12-week follow-up period. There were 30 men and 33 women, with a mean age of 58±11 (SD) [range: 34-81 years]. Compared with pre-procedure value, all post-procedure pain scores were significantly lower (P<0.0001). Likewise, there was a statistically significant reduction in daily morphine consumption at all follow-up times (P<0.0001). The ambulation score, ADL, and ODI were all significantly lower at all assessment times compared with pre-procedure values (P<0.0001). No serious adverse effects were observed. CONCLUSION: PVP using thick bone cement could be administered with reasonable safety to patients suffering from intractable pain caused by vertebral metastases who were at high risk for cement leakage. The procedure was associated with significant improvement of pain and disability.

Synthesis and biological evaluation of a new series of benzimidazole derivatives as antimicrobial, antiquorum-sensing and antitumor agents.

New benzimidazole derivatives were synthesized and assessed for antimicrobial efficacy toward Escherichia coli, Bacillus cereus, Staphylococcus aureus, Candida albicans and Aspergillus fumigatus 293. Results indicated that compounds 3c and 3n have promising activity toward S. aureus, whereas 3i exhibited remarkable efficacy toward B. cereus. Moreover, compound 3c was proved to be the most active antifungal analog toward C. albicans. On the other hand, 3n displayed the highest activity against A. fumigatus 293. Antiquorum-sensing activity of the same compounds was also tested against Chromobacterium violacium ATCC 12472, whereas compounds 3c-f, 3i-k and 3m-o showed acceptable activity. In vitro antitumor testing of these compounds toward liver cancer (HepG2), colon cancer (HCT-116) and breast cancer (MCF-7) cell lines revealed that compound 3p has the highest potency against the three tested cell lines. Moreover, 3f, 3m and 3n displayed promising activity toward all tested cell lines. Compounds 3f, 3m, 3n and 3p were esteemed for in vivo antitumor activity against EAC cells. The active antimicrobial and antitumor analogs, 3a, 3c, 3f, 3i-k, 3m, 3n and 3p were assessed for DNA-binding affinity, and results indicated that 3c, 3f, 3i, 3k and 3n have strong DNA-binding affinity. The computational studies affirmed that almost all of the inspected compounds meet the optimal requirements for good absorption and oral bioavailability.

Benign phyllodes tumours of the breast: (Over) treatment of margins - A literature review.

BACKGROUND: Phyllodes tumours form a small group of fibroepithelial breast lesions (2-3%). They are classified as benign, borderline, or malignant. (1). Benign phyllodes tumours are the largest subgroup of phyllodes tumours (50-80%), (2) A margin of 1 cm has been suggested as standard of care for all groups of phyllodes tumours.3-6 METHODS: We performed a literature review from January 2009 to April 2016 including the non-English literature. We compared studies taking a 1 mm margin, 10 mm margin and studies with focal margin involvement. RESULTS: We included 12 studies with overall 1702 patients. The range of therapeutic margins differed widely between studies. There is no consensus between studies what constitutes a clear or involved margin. There was a high percentage of margin involvement for benign phyllodes tumours (7.6-43.7%). Despite these inconsistencies, the recurrence rate after excision of benign phyllodes tumours was low in most studies (112 recurrences of 1052 benign phyllodes tumours - 11%; range 0-43%). There is no difference of the recurrence rate between studies aiming for a 10 mm margin (7.9%) compared to a 1 mm margin (5.7%) (p 0.124). The recurrence rate increases when there are tumour cells at the margin (12.9%) (p 0.006). CONCLUSION: There is no difference in recurrence rates between a 1 and a 10 mm margin. 1 mm is an acceptable margin for benign phyllodes tumours. The recurrence rate increases if there is focal margin involvement.

The relationship between the dimensions of the internal auditory canal and the anomalies of the vestibulocochlear nerve.

BACKGROUND: Internal auditory canal (IAC) stenosis and vestibulocochlear nerve (VCN) abnormalities have been reported to be associated with sensorineural hearing loss. Previous studies classified the normal dimensions of the IAC and its anomalies with no consideration of the VCN. Other studies categorised the VCN development in only stenotic canals. In the present study, an anatomical classification of the normal dimensions of the IAC and its anomalies and their association with malformations of the VCN and its subdivisions were described. MATERIALS AND METHODS: Retrospective review was undertaken for children ranged from 1 to 10 years. A total of 764 canals were investigated for pre-operative assessment of cochlear implantation. Other 100 canals of normal hearing ears were included as the control group. The maximum anteroposterior diameter, considered the width of the canal, was measured in axial plane and the length of the canal was identified in coronal plane. The canals were categorised normal: if they are from 3 to 8 mm, patulous: if they are more than 8 mm, stenotic: if they are less than 3 mm and atretic if absent, using multislice computed tomography. The VCN trunks and their subdivisions were investigated using magnetic resonance imaging. RESULTS: Internal auditory canals were found normal in 66% with a mean width: 5.27 ± ± 0.68, patulous in 17% with a mean width 113% more than that of the control group (p = 0.000), stenotic in 13% with a mean width 73% less as compared to that of the control group (p = 0.000) and atretic in 4% of the experimental canals. The VCN trunks were found normal with well-developed subdivisions in 77.8% of the normal canals, 98.4% of the patulous canals, and 19.2% of the stenotic canals. The VCN trunks were normal with hypoplastic subdivisions in 11.3% of the normal canals, 1.6% in the patulous canals, and 61.6% in the stenotic canals with a mean width 52% less than that of the normal trunk with developed subdivisions. Hypoplastic VCN trunks with absent subdivisions were reported in 7.3% of the normal canals, 11.1% of the stenotic canals and in 3.2% of the atretic canals. The VCN trunks were not found in 3.6% of the normal canals, in 8.1% of the stenotic canals and in 96.8% of the atretic canals. CONCLUSIONS: Internal auditory canal formation was dependent on the process of development and growth of the eighth cranial nerve and its subdivisions that greatly affected the completion of IAC canalisation. This paper could serve as a reference providing a quantitative classification of the relationship between the dimensions of the IAC and the development of the VCN trunk and its subdivisions.

Renin-Angiotensin-Aldosterone system blockade in diabetic kidney disease: A critical and contrarian point of view.

Diabetes mellitus is the most common cause of end-stage renal disease (ESRD) worldwide. Diabetic kidney disease (DKD) is associated with high morbidity and cardiovascular mortality. A number of guidelines and recommendations have been issued over the years recommending the use of renin-angiotensin-aldosterone system (RAAS) blockade in the management of DKD. This critical analysis takes a contrarian view, based on a selection of key clinical trials in the field, to argue that albuminuria should not be considered a target for treatment but instead a surrogate marker of DKD progression. The review also challenges, through a careful and critical analysis of a number of key clinical trials, the dogma that RAAS blockade's benefits in DKD is beyond mere good blood pressure control. While selective and somewhat biased the authors make compelling arguments to shed serious doubt over the strength of the evidence upon which the current guidelines favoring the use of RAAS blockade in DKD are based.

A study to establish international diagnostic reference levels for paediatric computed tomography.

The article reports results from the largest international dose survey in paediatric computed tomography (CT) in 32 countries and proposes international diagnostic reference levels (DRLs) in terms of computed tomography dose index (CTDI vol) and dose length product (DLP). It also assesses whether mean or median values of individual facilities should be used. A total of 6115 individual patient data were recorded among four age groups: <1 y, >1-5 y, >5-10 y and >10-15 y. CTDIw, CTDI vol and DLP from the CT console were recorded in dedicated forms together with patient data and technical parameters. Statistical analysis was performed, and international DRLs were established at rounded 75th percentile values of distribution of median values from all CT facilities. The study presents evidence in favour of using median rather than mean of patient dose indices as the representative of typical local dose in a facility, and for establishing DRLs as third quartile of median values. International DRLs were established for paediatric CT examinations for routine head, chest and abdomen in the four age groups. DRLs for CTDI vol are similar to the reference values from other published reports, with some differences for chest and abdomen CT. Higher variations were observed between DLP values, based on a survey of whole multi-phase exams. It may be noted that other studies in literature were based on single phase only. DRLs reported in this article can be used in countries without sufficient medical physics support to identify non-optimised practice. Recommendations to improve the accuracy and importance of future surveys are provided.

Subclinical sacroiliitis in brucellosis. Clinical presentation and MRI findings.

PURPOSE: The aim of this work was to detect subclinical sacroiliac joint involvement in patients with brucellosis and study their clinical and laboratory features. PATIENTS AND METHODS: The study included 100 brucellosis patients being followed-up in the Gastroenterology and Hepatology Unit, Theodor Bilharz Research Institute and Cairo University outpatient clinics. A thorough history, physical examination, routine laboratory tests, and abdominal ultrasound were obtained for all patients. Extended rheumatological examination was performed including clinical testing for sacroiliitis and enthesitis. None of the patients reported a history of back pain or any symptoms suggestive of sacroiliitis during the course of the infection. Plain x-ray and MRI scan of the sacroiliac joints were performed for all patients. RESULTS: Asymptomatic sacroiliitis was present in 24 % of the brucellosis patients; none of the patients had tenderness over their spine with preserved lumbar spine mobility. Sacroiliitis was mainly unilateral being bilateral in 20.83 %. There was an obvious relationship with animal contact and occupation of the patients. Osteoarticular involvement was common (67 %) including arthralgias, arthritis, myalgias, spondylitis, enthesitis and bursitis, being clearly higher in those with sacroiliitis. The MRI scan showed blurring of the margins in 66.67 %, widening in 25 %, narrowing in 54.17 %, erosions in 20.83 %, and sclerosis in 12.5 %. CONCLUSION: Osteoarticular manifestations of brucellosis are prevalent and subclinical sacroiliitis is evident, a finding that may classify these patients as having brucellar spondyloarthropathy (BSA). Referring brucellosis patients for rheumatological assessment has the advantage of early assessment of asymptomatic cases with sacroiliitis which is commonly overlooked.

Sodium ascorbate as a quorum sensing inhibitor of Pseudomonas aeruginosa.

AIMS: Quorum sensing circuits regulate virulence factors in Pseudomonas aeruginosa and coordinate bacterial pathogenicity. We are interested in exploring available medications for their antiquorum sensing activity. METHODS AND RESULTS: First, we determined the MIC of ascorbate against Ps. aeruginosa strain PAO1, and all further experiments used concentrations below the MIC so that results could not be caused by reduced viability. Tests of subinhibitory concentrations of sodium ascorbate on cell signals were performed using a reporter strain assay. Sub-MICs of sodium ascorbate resulted in significant reduction of the signalling molecules C4-HSL and 3-oxo-C12-HSL (P < 0·01). The influence of sub-MIC of sodium ascorbate on virulence factors was also determined and ascorbate treatment led to significant depression of elastase, protease and haemolysin activities. In addition, inhibition of pyocyanin production, attenuation of biofilm formation and alteration of Pseudomonas motility was observed. Analysis by RT-PCR tested the effect of ascorbate on the expression of QS regulatory genes. Expression of QS regulatory genes, lasI, lasR, rhlI, rhlR, pqsR and pqsA, was repressed compared to untreated Ps. aeruginosa PAO1, confirming that ascorbate QS inhibition works on gene expression at the molecular level. CONCLUSION: Sodium ascorbate, even at low concentrations, inhibited QS and related virulence factors of Ps. aeruginosa PAO1. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrated that sodium ascorbate could function as signal modulator and virulence inhibitor in Ps. aeruginosa.