Prospective exploratory muscle biopsy, imaging, and functional assessment in patients with late-onset Pompe disease treated with alglucosidase alfa: The EMBASSY Study

Background Late-onset Pompe disease is characterized by progressive skeletal myopathy followed by respiratory muscle weakness, typically leading to loss of ambulation and respiratory failure. In this population, enzyme replacement therapy (ERT) with alglucosidase alfa has been shown to stabilize respiratory function and improve mobility and muscle strength. Muscle pathology and glycogen clearance from skeletal muscle in treatment-naïve adults after ERT have not been extensively examined. Methods This exploratory, open-label, multicenter study evaluated glycogen clearance in muscle tissue samples collected pre- and post- alglucosidase alfa treatment in treatment-naïve adults with late-onset Pompe disease. The primary endpoint was the quantitative reduction in percent tissue area occupied by glycogen in muscle biopsies from baseline to 6 months. Secondary endpoints included qualitative histologic assessment of tissue glycogen distribution, secondary pathology changes, assessment of magnetic resonance images (MRIs) for intact muscle and fatty replacement, and functional assessments. Results Sixteen patients completed the study. After 6 months of ERT, the percent tissue area occupied by glycogen in quadriceps and deltoid muscles decreased in 10 and 8 patients, respectively. No changes were detected on MRI from baseline to 6 months. A majority of patients showed improvements on functional assessments after 6 months of treatment. All treatment-related adverse events were mild or moderate. Conclusions This exploratory study provides novel insights into the histopathologic effects of ERT in late-onset Pompe disease patients. Ultrastructural examination of muscle biopsies demonstrated reduced lysosomal glycogen after ERT. Findings are consistent with stabilization of disease by ERT in treatment-naïve patients with late-onset Pompe disease

Measurements of branching fractions, absolute transition probabilities and J-file sum rule for the 4p(5)5p -\u3e 4p(5)5s transitions array in neutral krypton

We present new results of transition rates for twenty two electric dipole transitions of neutral krypton associated with the 4p55p→4p55 s configurations-based levels covering the wavelength region from 500 to 1000 nm using a krypton filled hollow cathode discharge lamp coupled with a set of four miniature spectrometers. The branching fractions of various dipole allowed transitions were extracted using the observed line intensity ratios, whereas, the absolute values of the transition probabilities were deduced from the measured branching fractions in combination with the known lifetimes of the upper levels. The experimental data are in good agreement with that calculated in the intermediate angular momentum coupling scheme. In addition, line strengths for all the transitions have been extracted using the measured transition probabilities. The J-file sum rule was also tested for each level attached to the 4p55p→4p55 s configurations based on the recently measured and calculated normalized multiplet strengths

Industry 4.0 or Pharma 4.0?

This chapter examines the convergence of Industry 4.0 and Pharma 4.0 in the context of healthcare supply chains. It investigates the potential applications of these industrial revolutions to enhance the flexibility, benefits, challenges, and opportunities of healthcare supply chains. This chapter highlights the application of state-of-the-art technology to create intelligent, adaptable, and personalized supply chain systems for the healthcare and pharmaceutical sectors. The literature on “Pharma Industry 4.0” is reviewed, with a focus on the opportunities for sustainable value creation and pharmaceutical supply chain research. Healthcare supply chain has some serious issues like counterfeit drugs, non-transparent supply chain, unfear track and trace system of medicines and biomedical instruments. The authors identified the potential solutions for these issues with the help of current innovative technologies and practices

A Rare Presentation of Cardiac Aspergilloma in an Immunocompetent Host: Case Report and Literature Review

Cardiac aspergilloma is exceptionally rare with only a handful of cases reported and majority of them being in immunocompromised patients. Here, we present a case of cardiac aspergilloma involving the right and left ventricle in an immunocompetent patient that initially presented with acute limb ischemia. He was later found to have a cardiac mass with histopathological diagnosis confirming Aspergillus species. Despite aggressive medical and surgical interventions, the patient had an unfavorable outcome due to low suspicion of invasive fungal endocarditis given his immunocompetent status. Cardiac aspergilloma should remain in the differential diagnosis of immunocompetent patients as early clinical suspicion will result in early treatment and decreased mortality. Novel therapies are required to decrease mortality in the future from this fatal disease

Photoexcitation and photoionization from the 2p53p[5/2]2,3 levels in neon

We present measurements of the excitation spectra from the 2p53p [5/2]3,2 levels in neon using two-step laser excitation and ionization in conjunction with an optogalvanic detection in dc and rf discharge cells. The 2p53p [5/2]3,2 intermediate levels have been approached via the collisionally populated 2p53s [3/2]2 metastable level. The Rydberg series 2p5(2P3/2)nd [7/2]4 (12 ⩽ n ⩽ 44), 2p5(2P3/2)ns [3/2]2 (13 ⩽ n ⩽ 35) and the parity forbidden transitions 2p5(2P3/2)np [5/2]3 (13 ⩽ n ⩽ 19) have been observed from the 2p53p [5/2]3 level, whereas the 2p5(2P3/2)nd [7/2]3 (12 ⩽ n ⩽ 44), 2p5(2P3/2)ns [3/2]2 (13 ⩽ n ⩽ 35), and 2p5(2P1/2)nd′ [5/2]3 (9 ⩽ n ⩽ 12) Rydberg series have been observed from the 2p53p[5/2]2 level in accordance with the ΔJ = ΔK = ± 1 selection rules. The photoionization cross sections from the 2p53p [5/2]3 intermediate level have been measured at eight ionizing laser wavelengths (399, 395, 390, 385, 380, 370, 364, and 355 nm) and that from the 2p53p [5/2]2 level at 401.8 nm. These measurements are in excellent agreement with the experimental values reported in the literature, while the experimental data lie much below the theoretically calculated photoionization cross sections curve

Delicate Patterns of Colligations: A Corpus-based Study of Prepositions

The term colligation evidently highlights syntagmatic patterns of language. Basically, it investigates grammatical attractions between different lexical items based on their grammatical category (Firth, 1968). However, the concept collocation only discusses the lexical attraction between different lexicons. The aim of this study is to find out different colligations’patterns of preposition: to, in and into in native corpus of English language; LOCNESS. A quantitative approach has been underpinned in present study to find out grammatical patterns and their distribution. Benson et al. (1986) identified eight different grammatical collocations (colligations) in which the patterns G1, G5, and G8 particularly discussed distinctive colligation patterns of preposition. So, researcher follows this framework and tries to identify different colligation patterns of selected words to, in and into as preposition. For this purpose, corpus has been tagged by MAT tagger. The task of identification of different kind colligation patterns of selected words has been accomplished by corpus analysis toolkit AntConc 3.4 4. The findings notify us about the distribution of different kinds of colligation/grammatical patterns and their delicate offshoots. These colligations can be helpful for pedagogical purpose to teach ESL pupils about grammatical patterns of words rather than only rely on cramming based learning activities in the due to arbitrary nature of lexical collocations

Evaluation of Silicon Supplementation for Drought Stress under Water-Deficit Conditions: An Application of Sustainable Agriculture

Drought is a key abiotic stress that confines agriculture development worldwide. Silicon (Si) is commonly considered to be a valuable element for resistance against drought and for sustainable agriculture. To investigate the morpho-physiological and biochemical characteristics of Gerbera jamesonii plants, a pot experiment was conducted under greenhouse conditions and exposed to water stress (60% FC) and well-watered (100% FC) conditions. Foliar application of Si was carried out after ten days (48 days after sowing) of drought treatment and was repeated weekly, while well-water was regarded as control. Water deficiency significantly abridged the morphological attributes, pigments, and stress-related metabolites and negatively affected the photosynthetic apparatus in drought-stressed gerbera plants. However, Si supplementation by 40 mg L-1 produced increased leaf area (31%), stem length (25%), flower diameter (22%), plant fresh biomass (17%), total chlorophyll (48%), and concentration of carotenoids (54%) in water-stressed plants. Similarly, the accretion of a total free amino acid (41%) and the activities of peroxidase, catalase, superoxide dismutase, ascorbate peroxidase, glycinebetaine, total soluble proteins, total free proline, and malondialdehyde were enhanced by 44%, 31%, 53%, 33%, 330%, 61%, 51%, and 66%, respectively, under drought stress in comparison with control conditions. Meanwhile, the photosynthetic rate (89%), the transpiration rate (12%), and stomatal conductance (55%) were significantly enhanced in water-deficit gerbera leaves with Si supplementation. This study proposes that the foliar application of Si is a viable and convenient method of improving the performance of elegant gerbera flower plants in regions of the world that are facing severe water deficiency