Sodium valproate, a potential repurposed treatment for the neurodegeneration in Wolfram syndrome (TREATWOLFRAM): trial protocol for a pivotal multicentre, randomised double-blind controlled trial.

Introduction: Wolfram syndrome (Spectrum Disorder) is an ultra-rare monogenic form of progressive neurodegeneration and diabetes mellitus. In common with most rare diseases, there are no therapies to slow or stop disease progression. Sodium valproate, an anticonvulsant with neuroprotective properties, is anticipated to mediate its effect via alteration of cell cycle kinetics, increases in p21 expression levels and reduction in apoptosis and increase in Wolframin protein expression.

The benefits of flushing with Lemuru fish oil as a source of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on the performance of reproductive parameters in Garut ewes.

This study aimed to evaluate and analyze the effects of a flushing diet containing Docosahexaenoic acid (DHA) and Eicosapentaenoic acid (EPA) from Lemuru (Sardinella sp) fish oil on the reproductive performance parameters of Garut ewes. Forty (n = 40) primiparous Garut ewes aged 12-14 months with an average body weight of 28.92 ± 4.

Use of irradiated chitosan as a matrix for slow-release urea and fermentation characteristics of slow-release urea supplementation in ruminant rations.

Background And Aim: Irradiated chitosan can be used as a matrix for slow-release urea (SRU) production. This study aimed to (1) determine the optimal formulation of irradiated chitosan matrix for controlling nitrogen release and (2) evaluate the characteristics of SRU fermentation based on irradiated chitosan as a feed supplement.

Materials And Methods: In the first phase of the investigation, four chitosan-based SRU formulations with varying amounts of acrylamide (3 and 5 g) and gamma irradiation (5 and 10 kGy) were evaluated.

Utilization of Primary Health Care Under National Health Insurance in Samarinda Municipality, East Kalimantan Province, Indonesia.

Aim: In Indonesia, basic community health services are provided to all citizens through Primary Health Care (PHC) settings under the National Health Insurance (NHI) scheme. The insurance is compulsory and provides basic community health needs. Based on a gatekeeper concept, the PHC is deemed to be the first contact point for all basic healthcare needs.

Evaluation of rations containing bioconverted cacao pod as fiber source for small ruminant.

This study aimed to evaluate the potential use of bioconverted cacao pod (BCP) as a substitute for forage in the total mixed ration (TMR) for a small ruminant. In the in vitro experiment, the control TMR (30% forage and 70% concentrate) was substituted with two different levels of BCP (15% and 30%) and two different types of BCP ( BCP-pc and BCP-tv). Based on the in vitro evaluation, the best ration was then chosen for the in vivo experiment, in which male goats were fed a control TMR, the TMR containing 15% BCP-pc (RC), and TMR containing 15% bioconverted palm kernel meal (RP).

Analysis of autophagy deficiency and cytotoxicity in autophagy-deficient human embryonic stem cell-derived neurons.

Autophagy, a catabolic process governing cellular and energy homeostasis, is essential for cell survival and human health. Here, we present a protocol for generating autophagy-deficient (ATG5) human neurons from human embryonic stem cell (hESC)-derived neural precursors. We describe steps for analyzing loss of autophagy by immunoblotting.

The diversity and quality of forages and their potency as herbal anthelmintic for swamp buffalo in Brebes District, Central Java.

Background And Aim: Swamp buffaloes play an important role in the rural economy of Indonesia. They consume various forages during their grazing time, including those with anti-parasitic potential. However, the information about the type and quality of forages and their potential as a natural anthelmintic for swamp buffalo is very limited.

Depletion of WFS1 compromises mitochondrial function in hiPSC-derived neuronal models of Wolfram syndrome.

Mitochondrial dysfunction involving mitochondria-associated ER membrane (MAM) dysregulation is implicated in the pathogenesis of late-onset neurodegenerative diseases, but understanding is limited for rare early-onset conditions. Loss of the MAM-resident protein WFS1 causes Wolfram syndrome (WS), a rare early-onset neurodegenerative disease that has been linked to mitochondrial abnormalities. Here we demonstrate mitochondrial dysfunction in human induced pluripotent stem cell-derived neuronal cells of WS patients.

Atherosclerotic Lesion of the Carotid Artery in Indonesian Cynomolgus Monkeys Receiving a Locally Sourced Atherogenic Diet.

The atherosclerotic lesion is a principal hallmark of atherosclerotic animal models. This study aimed to assess lesions of the carotid artery in Indonesian cynomolgus monkeys exposed to an IPB-1 atherogenic diet. A total of 20 adult male cynomolgus monkeys received the local IPB-1 diet for two years.

Black soldier fly as feed ingredient for ruminants.

This paper is a review of some experiments using black soldier fly (BSF) and its by-product to explore their nutritional value, production potential in Indonesia and its application in the ration of ruminants. Evaluation on the effect of milk replacer, creep feed containing BSF, BSF frass and the possibility to use lactic acid bacteria from BSF as probiotics are presented. Utilization of BSF larvae in milk replacer as skim and cream milk substitute showed that there were similarity on physiological, hematological status and performance of goat kids compared to those offered goat milk or commercial milk replacer.

WFS1 protein expression correlates with clinical progression of optic atrophy in patients with Wolfram syndrome.

Background: Wolfram syndrome (WFS) is a rare disorder characterised by childhood-onset diabetes mellitus and progressive optic atrophy. Most patients have variants in the gene. We undertook functional studies of variants and correlated these with WFS1 protein expression and phenotype.

Stimulation of follicle growth and development during estrus in Ettawa Grade does fed a flushing supplement of different polyunsaturated fatty acids.

Background And Aim: Flushing with the manipulation of fatty acids, particularly polyunsaturated fatty acids, like linoleic and α-linolenic acids in the ration, is a strategy to raise the nutritional status of the female mammals to improve ovarian function and follicle development. This study was designed to investigate the effectiveness of flushing supplementation with different types of polyunsaturated and saturated fatty acids in stimulating follicle growth and development during estrus in Ettawa Grade does with a low initial body condition score (BCS ≤2).

Materials And Methods: Eighteen Ettawa Grade does in the second parity, with an average body weight of 32.

Prevalence and risk factors of trematode infection in swamp buffaloes reared under different agro-climatic conditions in Java Island of Indonesia.

Background And Aims: This study was conducted to estimate the prevalence and intensity and to identify the associated risk factors and impact of trematode infection in swamp buffaloes reared under different agro-climatic conditions in Java, Indonesia.

Materials And Methods: A total of 580 fecal samples were collected from swamp buffaloes in five different agro-climatic areas in Banten and Central Java Provinces, Indonesia. The fecal samples were examined using the Danish Bilharziasis Laboratory Technique to determine the prevalence and intensity of trematode infection.

Metabolic and morphometric changes in Indonesian cynomolgus monkeys (Macaca fascicularis) fed an atherogenic diet composed of locally sourced ingredients.

Background And Aim: This study was designed to determine the effects of a new atherogenic diet formulated at Institut Pertanian Bogor (IPB) (Bogor, Indonesia) on metabolic, morphometric, and carotid artery imaging of cynomolgus monkeys.

Materials And Methods: A total of 20 adult male cynomolgus monkeys fed IPB-1 atherogenic diet for 1 year. Total plasma cholesterol (TPC), high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, and morphometric measurements were evaluated at baseline and monthly during the study.

Monogenic diabetes syndromes: Locus-specific databases for Alström, Wolfram, and Thiamine-responsive megaloblastic anemia.

We developed a variant database for diabetes syndrome genes, using the Leiden Open Variation Database platform, containing observed phenotypes matched to the genetic variations. We populated it with 628 published disease-associated variants (December 2016) for: WFS1 (n = 309), CISD2 (n = 3), ALMS1 (n = 268), and SLC19A2 (n = 48) for Wolfram type 1, Wolfram type 2, Alström, and Thiamine-responsive megaloblastic anemia syndromes, respectively; and included 23 previously unpublished novel germline variants in WFS1 and 17 variants in ALMS1. We then investigated genotype-phenotype relations for the WFS1 gene.

Lowering Chitin Content of Cricket (Gryllus assimilis) Through Exoskeleton Removal and Chemical Extraction and its Utilization as a Ruminant Feed in vitro.

Background And Objective: Cricket contains high crude protein level but it also contains considerable amount of chitin that may impede nutrient digestion and decrease production performance of animal. This experiment aimed to decrease chitin content of cricket (C) through exoskeleton removal (CER) or by chemical extraction (CCE).

Materials And Methods: Nutritional evaluation of cricket was performed in two experiments.

Sarco(endo)plasmic reticulum ATPase is a molecular partner of Wolfram syndrome 1 protein, which negatively regulates its expression.

Wolfram syndrome is an autosomal recessive disorder characterized by neurodegeneration and diabetes mellitus. The gene responsible for the syndrome (WFS1) encodes an endoplasmic reticulum (ER)-resident transmembrane protein that is involved in the regulation of the unfolded protein response (UPR), intracellular ion homeostasis, cyclic adenosine monophosphate production and regulation of insulin biosynthesis and secretion. In this study, single cell Ca(2+) imaging with fura-2 and direct measurements of free cytosolic ATP concentration ([ATP]CYT) with adenovirally expressed luciferase confirmed a reduced and delayed rise in cytosolic free Ca(2+) concentration ([Ca(2+)]CYT), and additionally, diminished [ATP]CYT rises in response to elevated glucose concentrations in WFS1-depleted MIN6 cells.

Perlman syndrome: overgrowth, Wilms tumor predisposition and DIS3L2.

Perlman syndrome is a rare autosomal recessively inherited congenital overgrowth syndrome characterized by polyhydramnios, macrosomia, characteristic facial dysmorphology, renal dysplasia and nephroblastomatosis and multiple congenital anomalies. Perlman syndrome is associated with high neonatal mortality and, survivors have developmental delay and a high risk of Wilms tumor. Recently a Perlman syndrome locus was mapped to chromosome 2q37 and homozygous or compound heterozygous mutations were characterized in DIS3L2.

Vacuolar-type H+-ATPase V1A subunit is a molecular partner of Wolfram syndrome 1 (WFS1) protein, which regulates its expression and stability.

Wolfram syndrome is an autosomal recessive disorder characterized by neurodegeneration and diabetes mellitus. The gene responsible for the syndrome (WFS1) encodes an endoplasmic reticulum (ER)-resident transmembrane protein that also localizes to secretory granules in pancreatic beta cells. Although its precise functions are unknown, WFS1 protein deficiency affects the unfolded protein response, intracellular ion homeostasis, cell cycle progression and granular acidification.

Identification of homozygous WFS1 mutations (p.Asp211Asn, p.Gln486*) causing severe Wolfram syndrome and first report of male fertility.

Wolfram syndrome (WFS) is a neurodegenerative genetic condition characterized by juvenile-onset of diabetes mellitus and optic atrophy. We studied clinical features and the molecular basis of severe WFS (neurodegenerative complications) in two consanguineous families from Iran. A clinical and molecular genetic investigation was performed in the affected and healthy members of two families.

Germline mutations in DIS3L2 cause the Perlman syndrome of overgrowth and Wilms tumor susceptibility.

Perlman syndrome is a congenital overgrowth syndrome inherited in an autosomal recessive manner that is associated with Wilms tumor susceptibility. We mapped a previously unknown susceptibility locus to 2q37.1 and identified germline mutations in DIS3L2, a homolog of the Schizosaccharomyces pombe dis3 gene, in individuals with Perlman syndrome.

Mutation analysis of HIF prolyl hydroxylases (PHD/EGLN) in individuals with features of phaeochromocytoma and renal cell carcinoma susceptibility.

Germline mutations in the von Hippel-Lindau disease (VHL) and succinate dehydrogenase subunit B (SDHB) genes can cause inherited phaeochromocytoma and/or renal cell carcinoma (RCC). Dysregulation of the hypoxia-inducible factor (HIF) transcription factors has been linked to VHL and SDHB-related RCC; both HIF dysregulation and disordered function of a prolyl hydroxylase domain isoform 3 (PHD3/EGLN3)-related pathway of neuronal apoptosis have been linked to the development of phaeochromocytoma. The 2-oxoglutarate-dependent prolyl hydroxylase enzymes PHD1 (EGLN2), PHD2 (EGLN1) and PHD3 (EGLN3) have a key role in regulating the stability of HIF-α subunits (and hence expression of the HIF-α transcription factors).

Analysis of VHL Gene Alterations and their Relationship to Clinical Parameters in Sporadic Conventional Renal Cell Carcinoma.

PURPOSE: This study aimed to carry out a comprehensive analysis of genetic and epigenetic changes of the von Hippel Lindau (VHL) gene in patients with conventional (clear cell) renal cell carcinoma and to determine their significance relative to clinicopathologic characteristics and outcome. EXPERIMENTAL DESIGN: The VHL status in 86 conventional renal cell carcinomas was determined by mutation detection, loss of heterozygosity (LOH), and promoter methylation analysis, extending our original cohort to a total of 177 patients. Data were analyzed to investigate potential relationships between VHL changes, clinical parameters, and outcome.

Germline SDHB mutations and familial renal cell carcinoma.

Familial renal cell carcinoma (RCC) is a heterogeneous disorder that is most commonly caused by germline mutations in the VHL, MET, and FLCN genes or by constitutional chromosome 3 translocations. However, for many patients with familial RCC, the genetic basis of the disease is undefined. We investigated whether germline mutations in fumarate hydratase (FH) or succinate dehydrogenase subunit genes (SDHB, SDHC, SDHD) were associated with RCC susceptibility in 68 patients with no clinical evidence of an RCC susceptibility syndrome.