The Effects of Incubation Length and Temperature on the Specificity and Sensitivity of the BANA (N‐Benzoyl‐DL‐Arginine‐Naphthylamide) Test

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141244/1/jper0848.pd

Potential of Endangered Local Donkey Breeds in Meat and Milk Production

The problem of the erosion of animal genetic resources is evident in certain local donkey breeds, and their long-term sustainability can be achieved by economically repositioning them. To develop alternative and sustainable commercial programs, the meat and milk production characteristics of Istrian donkey and Littoral Dinaric donkey breeds were investigated. The meat production characteristics were examined in mature males, whose carcasses were dissected, and meat composition was determined using NIT spectrophotometry and gas chromatography. Milk yield and milk composition were determined in jennies in second or subsequent lactations by measuring milk volume and using infrared spectrometry and gas chromatography. Compared to the Littoral Dinaric donkey, the Istrian donkey has a higher carcass weight and dressing percentage (p < 0.001). The share of boneless meat in relation to live weight was 28.27% in the Istrian donkey and 26.18% in the Littoral Dinaric donkey. The absolute masses of primal cuts of meat in E, I, and II classes were significantly greater in Istrian donkeys than in Littoral Dinaric donkeys (p < 0.01), although the differences in the proportions of primal cuts were not significant. The breed did not have a significant impact on the color, pH, or meat composition. A significant influence of breed on milk yield, lactose, protein, and the fat content of milk was observed (p < 0.01). A significant influence of breed on the ratio of n-6/n-3 PUFA fatty acids in donkey milk was observed (p = 0.002). The values of the atherogenic and thrombogenic indexes were favorable, considering potential beneficial effects of donkey milk and meat on consumer health. The findings of this research suggest that local donkey breeds hold significant potential for meat and milk production, focusing on the uniqueness and quality of their products rather than the quantity of meat and milk they can produce

Dissolved organic matter in continental hydro-geothermal systems: insights from two hot springs of the East African Rift valley

Little is known about the quantity and quality of dissolved organic matter (DOM) in waters from continental geothermal systems, with only a few reports available from the Yellowstone US National Park. In this study, we explored the chemodiversity of DOM in water samples collected from two geothermal hot springs from the Kenyan East African Rift Valley, a region extremely rich in fumaroles, geysers, and spouting springs, located in close proximity to volcanic lakes. The DOM characterization included in-depth assessments performed by negative electrospray ionization Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). Reduced, saturated and little aromatic DOM compounds were dominant in the hot spring waters collected from either the Ol Njorowa gorge (ON) or the south shore of the soda-saline Lake Elementaita (ELM). Oxygen-poor and sulfur-bearing DOM molecules prevailed in ON, probably reflecting abiotic sulfurization from sulfide-rich geofluids. Nitrogen-bearing aliphatic and protein-like molecules were abundant in ELM, possibly perfusing through the organic-rich sediments of the adjacent Lake Elementaita. Notably, the heat-altered DOM of ancient autochthonous derivation could represent an overlooked source of aliphatic organic carbon for connected lentic environments, with a potential direct impact on nutrient cycling in lakes that receive geothermal water inputs

A New Adenovirus Based Vaccine Vector Expressing an Eimeria tenella Derived TLR Agonist Improves Cellular Immune Responses to an Antigenic Target

Adenoviral based vectors remain promising vaccine platforms for use against numerous pathogens, including HIV. Recent vaccine trials utilizing Adenovirus based vaccines expressing HIV antigens confirmed induction of cellular immune responses, but these responses failed to prevent HIV infections in vaccinees. This illustrates the need to develop vaccine formulations capable of generating more potent T-cell responses to HIV antigens, such as HIV-Gag, since robust immune responses to this antigen correlate with improved outcomes in long-term non-progressor HIV infected individuals.. Moreover, we show that these improved responses were dependent upon improved TLR pathway interactions.The data presented in this study illustrate the potential utility of Ad-based vectors expressing TLR agonists to improve clinical outcomes dependent upon induction of robust, antigen specific immune responses

Dystrophin expression in muscle following gene transfer with a fully deleted ("Gutted") adenovirus is markedly improved by Trans-acting adenoviral gene products

Helper-dependent adenoviruses (HDAd) are Ad vectors lacking all or most viral genes. They hold great promise for gene therapy of diseases such as Duchenne muscular dystrophy (DMD), because they are less immunogenic than E1/E3-deleted Ad (first-generation Ad or FGAd) and can carry the full-length (Fl) dystrophin (dys) cDNA (12 kb). We have compared the transgene expression of a HDAd (HDAdCMVDysFl) and a FGAd (FGAdCMV-dys) in cell culture (HeLa, C2C12 myotubes) and in the muscle of mdx mice (the mouse model for DMD). Both vectors encoded dystrophin regulated by the same cytomegalovirus (CMV) promoter. We demonstrate that the amount of dystrophin expressed was significantly higher after gene transfer with FGAdCMV-dys compared to HDAdCMVDysFl both in vitro and in vivo. However, gene transfer with HDAdCMVDysFl in the presence of a FGAd resulted in a significant increase of dystrophin expression indicating that gene products synthesized by the FGAd increase, in trans, the amount of dystrophin produced. This enhancement occurred in cell culture and after gene transfer in the muscle of mdx mice and dystrophic golden retriever (GRMD) dogs, another animal model for DMD. The E4 region of Ad is required for the enhancement, because no increase of dystrophin expression from HDAdCMVDysFl was observed in the presence of an E1/E4-deleted Ad in vitro and in vivo. The characterization of these enhancing gene products followed by their inclusion into an HDAd may be required to produce sufficient dystrophin to mitigate the pathology of DMD by HDAd-mediated gene transfer

Are Patient Self-Reported Outcome Measures Sensitive Enough to Be Used as End Points in Clinical Trials?: Evidence from the United Kingdom Glaucoma Treatment Study

Purpose The United Kingdom Glaucoma Treatment Study (UKGTS) demonstrated the effectiveness of an intraocular pressure-lowering drug in patients with glaucoma using visual field progression as a primary outcome. The present study tested the hypothesis that responses on patient-reported outcome measures (PROMs; secondary outcome measure) differ between patients receiving a topical prostaglandin analog (latanoprost) or placebo eye drops in UKGTS. Design Multicenter, randomized, triple-masked, placebo-controlled trial. Participants Newly diagnosed glaucoma patients in the UKGTS with baseline and exit PROMs (n = 182 and n = 168 patients from the treatment and placebo groups, respectively). Methods In the UKGTS (trial registration number, ISRCTN96423140), patients with open-angle glaucoma were allocated to receive latanoprost (treatment) or placebo; the observation period was 24 months. Patients completed general health PROMs (European Quality of Life in 5 Dimensions [EQ-5D] and 36-item Short Form [SF-36]) and PROMs specific to glaucoma (15-item Glaucoma Quality of Life [GQL-15] and 9-item Glaucoma Activity Limitation [GAL-9]) at baseline and exit from the trial. Percentage changes between measurement on PROMs were calculated for each patient and compared between treatment arms. In addition, differences between stable patients (n = 272) and those with glaucomatous progression (n = 78), as determined by visual field change (primary outcome), were assessed. Main Outcome Measure PROMs on health-related and vision-related quality of life. Results Average percentage change on PROMs was similar for patients in both arms of the trial, with no statistically significant differences between treatment and placebo groups (EQ-5D, P = 0.98; EQ-5D visual analog scale, P = 0.88; SF-36, P = 0.94, GQL-15, P = 0.66; GAL-9, P = 0.87). There were statistically significant differences between stable and progressing patients on glaucoma-specific PROMs (GQL-15, P = 0.02; GAL-9, P = 0.02), but not on general health PROMs (EQ-5D, P = 0.62; EQ-5D visual analog scale, P = 0.23; SF-36, P = 0.65). Conclusions Average change in PROMs on health-related and vision-related quality of life was similar for the treatment and placebo groups in the UKGTS. The PROMs used may not be sensitive enough to function as primary end points in clinical trials when participants have newly diagnosed early-stage glaucoma

Kinetin riboside and its ProTides activate the Parkinson's disease associated PTEN-induced putative kinase 1 (PINK1) independent of mitochondrial depolarization

Since loss of function mutations of PINK1 lead to early-onset Parkinson’s disease, there has been growing interest in the discovery of small molecules that amplify the kinase activity of PINK1. We herein report the design, synthesis, serum stability and hydrolysis of four kinetin riboside ProTides. These ProTides, along with kinetin riboside, activated PINK1 in cells independent of mitochondrial depolarization. This highlights the potential of modified nucleosides and their phosphate prodrugs as treatments for neurodegenerative diseases

Hearing in adults with Pompe disease

Hearing loss has been recognized as an important cause of morbidity in infants with Pompe disease, a metabolic disorder caused by deficiency of acid α-glucosidase. It is unknown whether hearing is also affected in adult Pompe patients. We have studied the prevalence, severity, and type of hearing loss in 58 adult patients using tympanometry and pure-tone audiometry. Compared to normative data (International Organisation for Standardisation standard 7029), 72% of patients had impaired hearing thresholds at one or more frequencies in at least one ear. All measured frequencies were equally affected. All patients had a sensorineural type of hearing loss, pointing to cochlear or retrocochlear pathology. Categorised according to the standards of the World Health Organisation 21% of patients had a clinically relevant hearing loss (16% slight, 3% moderate, 2% profound). Though this suggests that hearing loss occurs in a considerable number of patients with Pompe disease, this prevalence is similar to that in the general population. Therefore, we conclude that hearing loss is not a specific feature of Pompe disease in adults

Facial-muscle weakness, speech disorders and dysphagia are common in patients with classic infantile Pompe disease treated with enzyme therapy

Classic infantile Pompe disease is an inherited generalized glycogen storage disorder caused by deficiency of lysosomal acid α-glucosidase. If left untreated, patients die before one year of age. Although enzyme-replacement therapy (ERT) has significantly prolonged lifespan, it has also revealed new aspects of the disease. For up to 11 years, we investigated the frequency and consequences of facial-muscle weakness, speech disorders and dysphagia in long-term survivors. Sequential photographs were used to determine the timing and severity of facial-muscle weakness. Using standardized articulation tests and fibreoptic endoscopic evaluation of swallowing, we investigated speech and swallowing function in a subset of patients. This study included 11 patients with classic infantile Pompe disease. Median age at the start of ERT was 2.4 months (range 0.1-8.3 months), and median age at the end of the study was 4.3 years (range 7.7 months −12.2 years). All patients developed facial-muscle weakness before the age of 15 months. Speech was studied in four patients. Articulation was disordered, with hypernasal resonance and reduced speech intelligibility in all four. Swallowing function was studied in six patients, the most important findings being ineffective swallowing with residues of food (5/6), penetration or aspiration (3/6), and reduced pharyngeal and/or laryngeal sensibility (2/6). We conclude that facial-muscle weakness, speech disorders and dysphagia are common in long-term survivors receiving ERT for classic infantile Pompe disease. To improve speech and reduce the risk for aspiration, early treatment by a speech therapist and regular swallowing assessments are recommended