Fumaric acid ester–induced renal Fanconi syndrome: evidence of mitochondrial toxicity

Background: Fumaric acid esters (FAEs) are used to treat chronic plaque psoriasis. Fumarate is a crucial component of the Krebs cycle and mitochondrial function. Proximal tubule cells have high energy demands and rely on aerobic respiration. Proximal tubular dysfunction can cause renal Fanconi syndrome and acute kidney injury. We sought to better understand the mechanism for this in the context of FAE therapy. Methods: We describe a case series of 10 patients with FAE-associated Fanconi syndrome. Patients were diagnosed and managed at a tertiary renal tubular disorder clinic, with examination of serum and urine biochemistry. Five patients had a renal biopsy with examination of the specimens by electron microscopy. Results: The median age was 36.5 years [interquartile range (IQR) 32.25–54.25]. The median dose of FAE was 720 mg/day (IQR 390–720). There was low molecular weight proteinuria: the median urinary retinol-binding protein (RBP) at presentation was 8385 μg/mL (IQR 2793–14 600) and the RBP:creatinine ratio was 710 (IQR 390–2415). All patients had hyperphosphaturia [median fractional excretion of phosphate 24.2% (IQR 20.8–26.9), normal range <20%] as well as relative hypophosphataemia, with a median serum phosphate concentration of 0.93 mmol/L (IQR 0.83–0.97). Renal histology showed proximal tubular damage and abnormal mitochondrial morphology. Two patients had a favourable biochemical response to treatment with probenecid. Conclusions: We document for the first time that FAE-associated renal Fanconi syndrome is associated with mitochondrial damage visible on electron microscopy. This effect may be ameliorated by antagonism of the organic anion transporter with probenecid

Effects of electron beam radiation on trait mutation in azuki bean (Vigna angularisi)

Dry seeds of azuki bean (Vigna angularisi), Jingnong 6 and Hebei 801 varieties were irradiated by electron beam of 100, 300, 600, 700 and 900 Gy, respectively. Mutations of leaf shape and color, seed size and shape, trailing, more branching, dwarfing, early or late flowering time and high yield were created in M2 and M3 generations. There were richest variations in Jinnong 6 treated with 600 Gy. Heibei 801 was more sensitive to electron beam radiation than Jingnong 6; more mutation types were produced at 100, 300 and 600 Gy. The pod number per plant, seed number and yield per plant of Jinnong 6 displayed a strikingly negative correlation to radiation dose, while the pod length, pod width, and 100-seeds weight of progenies from Hebei 801 had a significantly negative correlation with the radiation dose, but pod number per plants showed significantly positive correlation. Few of the normal phenotype plant in M2 generation derived mutants of new leaf yellowing, narrow leaf, clustering flower and leaf, kidney or sword leaf in M3 generation. Mutants of kidney and sword leaf, early flowering time from M2 generation could be stably inherited in M3 generation.Keywords: Azuki bean (Vigna angularisi), electron beam radiation, trait mutatio

eLingua : Issue 1 : March 2014 / Academy of Language Studies

1. “MESRA CERIA” Programme with children of Rumah Kanak-kanak Taman : A total of 35 staff members of The Academy of Language Studies, UiTM Pulau Pinang participated in a community programme called Program Mesra Ceria Bersama Kanak-kanak Rumah Kanak- kanak Taman Bakti on 22 June 2013. This event took place at a welfare home for the neglected and abused children as young as a newborn to as old as 12 years. 92 children were involved in this programme. 2. UiTMPP Inter-Department Indoor Sports Competition : During the recent inter-department indoor sports competition, the Academy of Lan¬guage Studies (ALS) joined forces with PSM, USMB, and ACIS to compete in several indoor sports at UiTM’s main hall. ALS lecturers, Mr Lim Soo Giap, Ms Nurul Bazilah Abd Hamid and Ms Syarifah Norrasyidah Syed Mohri, represented ALS in the badminton doubles while Ms Farhana Shukor represented ALS in the ping-pong competition. 3. ALS Aidilfitri and Deepavali ‘Open House’ : On the 30th August 2013, the department decided to host its ‘Open House’ to celebrate Hari Raya Aidilfitri and Deepavali Day at UiTM Pulau Pinang Hotel. The main objectives of this event were to strengthen relationships between the faculty members and spending a bit of ‘time- off from work to be with col¬leagues. As we have not had such gatherings for quite some time, most of us were looking forward to it. We had such a good time ‘karaoke-ing’ over lunch! We were spoilt for choice when it came to eating; satay, rendang, ketupat, fried beehoon, soto, pizza, cakes, cookies, ice cream, pastries and many more. 4. Kudos to the ALS Faculty Members! : With the unique theme of ‘takeoff and landing’ concept, The Faculty of Hotel and Tourism Management hosted UiTM Penang 2013 Hari Kualiti on December 20th, 2013. ALS UiTM Pulau Pinang had a very good reason to celebrate the day as several of its faculty members were awarded in various categories such as publications, services and innovation. Kudos to Dr. Rushita Ismail, Prof. Madya Hoe Foo Terng, Ms Agelyia Murugan, Mr Budiman Sabri Ahmad, Ms Emily Jothee Mathai, Ms Er Ann Nah, Ms Farina Nozakiah Tazijan, Ms Hanani Ahmad Zubir, Mr Liaw Shun Chone, Mr Lim Teck Heng, Mr Mah Boon Yih, Ms Muriatul Khusmah Musa, Ms Norhafizah Abd Halil, Ms Ong Sheau Fen, Mr Rasaya Marimuthu, Ms Syahirah Ramli, Ms Suzana Ab Rahim, Ms Wan Noorli Razali, Ms Wan Syakira Meor Hissan and Mr Fazrul Azmi Zulkifli. 5. 2nd UPALS ICL 2013 : Academy of Language Studies, UiTM Pulau Pinang had successfully organized its Second International Conference on Languages, the 2nd UPALS ICL 2013 at Traders Hotel, Georgetown, Penang from 29th to 31st May 2013. With the theme “Language in Diverse Environments”, the conference had become a plat¬form for academicians, researchers, practitioners, programme providers and students to share the latest devel¬opment in language teaching and learning in various settings. It had managed to capture the interest of not only the local but also international presenters and participants. Associate Professor Mohd Zaki Abdullah, the former UiTM Pulau Pinang Rector officiated the conference opening ceremony. 6. COLT 2013 : The 2nd International Conference of Language & Teaching (COLT) was held on 7 and 8 November, 2013 at the Park Royal Hotel, Batu Fer- inghi, Penang. It was organized by the Department of Language Studies, Universiti Teknologi MARA Kedah and the opening ceremony was officiated none other by our UiTM Pro-Chancellor, Yang Berbahagia Tan Sri Dato’ Seri Utama Arshad Ayub. The keynote speakers were Prof. Dr. Rod Ellis and Prof. Dr. Ania Lian while the first and second plenary sessions were headed again by Yang Berbahagia Tan Sri Dato Seri Utama Arshad Ayub and Associate Professor Dr. Saadiyah Darus respectively. The conference themed ‘Passing the Baton: Revitalising, Preserving and Sustaining Languages of the World’ attracted 63 papers. From APB UiTM Pulau Pinang itself, there were 4 presenters. 7. A Splash of French Culture : Students from Universiti Teknologi MARA Pulau Pinang were recently given the opportunity to take part in a poster drawing competition orga¬nized by the French Club of the university. Opened to all, students eagerly picked up their long abandoned colour pencils and crayons to rekindle their passion for drawing. The contest which started on the 13th of January and ended on the 7th of February saw an interesting number of partic¬ipants. The theme of the competition revolved around the French culture with a slogan in French. A multitude of skills was applied, intense col¬ors splashed and coupled with a vivid imagination, a vibrant and vivid French cultural landscape was aptly portrayed. On the 14th of February, ten judges from the Academy of Language Studies were invited to choose the winners of the contest. The posters were judged based on five criteria: innovation, imagination, image content, wording and commitment of the participants. 8. Pengenalan Cara Penciptaan Tulisan Cina (Liu Shu) : Skrip Bahasa Cina adalah satu sistem penulisan ideografik, di mana struktur grafik secara langsung berkaitan dengan pengertian. Oleh itu, langkah pertama ke arah penguasaan karaktor Cina adalah untuk mempelajari ciri-ciri komposisi mereka. Dalam kajian komposisi karaktor Cina, terdapat teori tradisional yang dikenali sebagai Liu Shu (enam cara penciptaan tulisan Cina). 9. What a wordie!! : all me crazy but I have been playing word games since I was twelve. Memorizing words and their spellings from a dictionary were what my brother and I together with the next-door teenagers did best before any games played. We were really enthusiastic get¬ting fully prepared for our next scrabble competition. There we were, Duan and Razak, Zamri and I at the hallway of our house. We were the word ad¬dicts in the neighborhood

Machine Learning to Identify Genetic Salt-Losing Tubulopathies in Hypokalemic Patients

Introduction: Clinically distinguishing patients with the inherited salt-losing tubulopathies (SLTs), Gitelman or Bartter syndrome (GS or BS) from other causes of hypokalemia (LK) patients is difficult, and genotyping is costly. We decided to identify clinical characteristics that differentiate SLTs from LK. Methods: A total of 66 hypokalemic patients with possible SLTs were recruited to a prospective observational cohort study at the University College London Renal Tubular Clinic, London. All patients were genotyped for pathogenic variants in genes which cause SLTs; 39 patients had pathogenic variants in genes causing SLTs. We obtained similar data sets from cohorts in Taipei and Kobe, as follows: the combined data set comprised 419 patients; 291 had genetically confirmed SLT. London and Taipei data sets were combined to train machine learning (ML) algorithms, which were then tested on the Kobe data set. Results: Single biochemical variables (e.g., plasma renin) were significantly, but inconsistently, different between SLTs and LK in all cohorts. A decision table algorithm using serum bicarbonate and urinary sodium excretion (FENa) achieved a classification accuracy of 74%. This was superior to all the single biochemical variables identified previously. Conclusion: ML algorithms can differentiate true SLT in the context of a specialist clinic with some accuracy. However, based on routine biochemistry, the accuracy is insufficient to make genotyping redundant

Effects of Early Intervention With Maternal Fecal Bacteria and Antibiotics on Liver Metabolome and Transcription in Neonatal Pigs

The establishment of a stable bacterial flora in early life is associated with host metabolism. Studies of fecal microbiota transplantation (FMT) and antibiotics on neonatal pig mainly focused on intestinal development and mucosal immunity, but the information on metabolism is lacking. The objective of this study was to investigate the responses of metabolome and transcriptome in the livers of neonatal piglets that were orally inoculated with maternal fecal bacteria suspension and amoxicillin (AM) solution. Five litters of Duroc × Landrace × Yorkshire neonatal piglets were used as five replicates and nine piglets in each litter were randomly assigned to the control (CO), AM or FMT groups. Neonatal piglets in three groups were fed with 3 mL saline (0.9%), AM solution (6.94 mg/mL) or fecal bacteria suspension (&gt;109/mL), respectively, on days 1–6. At the age of 7 and 21 days, one piglet from each group in each litter was sacrificed, and the serum and liver were collected for analysis. The RNA sequencing analysis showed that the mRNA expressions of arachidonate 12-lipoxygenase (ALOX12), acetyl-CoA acyltransferase 2 (ACAA2), cytochrome P450 family 1 subfamily A member 2 (CYP1A2), glutamic–pyruvic transaminase 2 (GPT2) and argininosuccinate synthase 1 (ASS1) were downregulated (P &lt; 0.05) by AM on day 7, and that the mRNA expressions of arachidonate 15-lipoxygenase (ALOX15), CYP1A2 and GPT2 were downregulated (P &lt; 0.05) by FMT on day 7. GC-MS analysis showed that AM and FMT treatments mainly affected fatty acid metabolism and amino acid metabolism on days 7 and 21. AM and FMT both reduced (P &lt; 0.05) the blood levels of triglycerides and low density lipoprotein cholesterol (LDL-C) on day 7. AM reduced (P &lt; 0.05) the blood level of cholesterol on day 21, and FMT reduced the blood levels of cholesterol, triglycerides and LDL-C on day 21. These results indicate that early intervention with FMT or AM can reduce fatty acid oxidative catabolism and amino acid biosynthesis of neonatal piglets, which provides a reference for regulation host metabolism through early intervention in animal production and even human health

Skepticism and Euroskepticism in British Politics

This article provides an analysis of the variants of Euroskepticism voiced in the British political discourse on furthering integration of the United Kingdom with Europe

MASEP gamma knife radiosurgery for secretory pituitary adenomas: experience in 347 consecutive cases

<p>Abstract</p> <p>Background</p> <p>Secretory pituitary adenomas are very common brain tumors. Historically, the treatment armamentarium for secretory pituitary adenomas included neurosurgery, medical management, and fractionated radiotherapy. In recent years, MASEP gamma knife radiosurgery (MASEP GKRS) has emerged as an important treatment modality in the management of secretory pituitary adenomas. The goal of this research is to define accurately the efficacy, safety, complications, and role of MASEP GKRS for treatment of secretory pituitary adenomas.</p> <p>Methods</p> <p>Between 1997 and 2007 a total of 347 patients with secretory pituitary adenomas treated with MASEP GKRS and with at least 60 months of follow-up data were identified. In 47 of these patients some form of prior treatment such as transsphenoidal resection, or craniotomy and resection had been conducted. The others were deemed ineligible for microsurgery because of body health or private choice, and MASEP GKRS served as the primary treatment modality. Endocrinological, ophthalmological, and neuroradiological responses were evaluated.</p> <p>Results</p> <p>MASEP GKRS was tolerated well in these patients under the follow-up period ranged from 60 to 90 months; acute radioreaction was rare and 17 patients had transient headaches with no clinical significance. Late radioreaction was noted in 1 patient and consisted of consistent headache. Of the 68 patients with adrenocorticotropic hormone-secreting(ACTH) adenomas, 89.7% showed tumor volume decrease or remain unchanged and 27.9% experienced normalization of hormone level. Of the 176 patients with prolactinomas, 23.3% had normalization of hormone level and 90.3% showed tumor volume decrease or remain unchanged. Of the 103 patients with growth hormone-secreting(GH) adenomas, 95.1% experienced tumor volume decrease or remain unchanged and 36.9% showed normalization of hormone level.</p> <p>Conclusion</p> <p>MASEP GKRS is safe and effective in treating secretory pituitary adenomas. None of the patients in our study experienced injury to the optic apparatus or had other neuropathies related with gamma knife. MASEP GKRS may serve as a primary treatment method in some or as a salvage treatment in the others. However, treatment must be tailored to meet the patient's symptoms, tumor location, tumor morphometry, and overall health. Longer follow-up is required for a more complete assessment of late radioreaction and treatment efficacy.</p