This study explores the lived phenomenon of customer experience (CX) across the customer decision journey of two divergent segments of customers in a naturalistic environment. Specifically, the study ...focusses on understanding the similarities and differences with respect to—(a) dimensions of CX, (b) consequences of CX, (c) moderators of CX, and (d) situating CX in customer decision journey. The findings are in congruence with the various theories from cognitive psychology, environmental psychology, and economic geography. The findings contribute to existing research that is primarily focussed on conceptualizing and measuring CX by providing an in-depth analysis of its formation for these two customer segments. Managers can utilize the findings to identify these touchpoints that lead to relevant customer responses. In all, the propositions drawn from the study findings are assimilated in the theoretical framework that adds to the nascent research on CX and customer decision journey.
Mesenchymal stem cells‐conditioned media (MSCs‐CM) contains several growth factors and cytokines, thus may be used as a better alternative to stem cell therapy, which needs to be elucidated. The ...present study was conducted to evaluate the therapeutic potential of caprine, canine, and guinea pig bone marrow‐derived MSCs‐CM in excision wound healing in a guinea pig model. MSCs were obtained from bone marrow, expanded ex vivo and characterized as per ISCT criteria. CM was collected assayed by western blot to ascertain the presence of important secretory biomolecules. Quantitative estimation by enzyme‐linked immunosorbent assay was done for a vascular epidermal growth factor (VEGF) and interleukin‐6 (IL‐6) in caprine MSCs‐CM and optimum time for collection of CM was decided as 72 hr. CM from all the species was lyophilized by freeze‐drying method. Full‐thickness (2 × 2 cm2) excision skin wounds were created in guinea pigs (six animals in each group) and respective lyophilized CM mixed with laminin gel was applied topically at weekly interval. On Day 28, histopathological examinations of healed skin were done by hemotoxylin and eosin staining. MSCs were found to secrete important growth factors and cytokines (i.e., VEGF, transforming growth factor‐β1, fibroblast growth factor‐2, insulin‐like growth factor‐1, stem cell factor, and IL‐6) as demonstrated by immunohistochemistry and western blot assay. It was found that allogenic and xenogenic application of CM significantly improved quality wound healing with minimal scar formation. Thus, MSCs‐CM can be used allogenically as well as xenogenically for quality wound healing.
Mesenchymal stem cells‐conditioned media (MSCs‐CM) contains important biomolecules.
Lyophilized MSCs‐CM mixed with gel can be applied allogenically as well as xenogenically for quality wound healing.
It has better application than MSCs like; can be used fresh, lyophilized and stored at 4°C or −20°C, can be used in the form of gel‐like formulations, and at field level, it can be used by semiskilled personnel also.
Reduced levels of brain gangliosides GD1a, GD1b, GT1b and to a lesser extent GM1 have been found in substantia nigra (SN) from Parkinson's disease (PD) patients, along with decreased gene expression ...for key enzymes (B3Galt4, St3gal2) involved in synthesis of these gangliosides. Based on these observations, the present study examined the extent to which decreased expression of B3GALT4 mRNA and resulting decreased levels of GM1 ganglioside in dopaminergic cells may increase the vulnerability of these cells to degeneration in response to a neurotoxicant exposure that under normal circumstances would not result in neurodegeneration. Differentiated SK-N-SH cells were treated with B3GALT4 siRNA to significantly reduce B3GALT4 mRNA expression and decrease GM1 levels. Exposure of these cells to a low concentration (10 μM) of the neurotoxin MPP+ that previously produced no toxicity resulted in approximately 50% cell loss after B3GALT4 siRNA treatment. This was a similar a degree of cell loss observed with 100 μM MPP+ in normal, differentiated SK-N-SH cells. Addition of GM1 to the culture medium after siRNA treatment was able to significantly protect cells from enhanced MPP+ toxicity. These data suggest that decreased B3GALT4 and GM1 expression can increase cell vulnerability to potentially toxic stressors and that such mechanisms may contribute to dopaminergic neurodegeneration in PD.
•B3GALT4 siRNA significantly reduced B3GALT4 mRNA expression.•B3GALT4 siRNA significantly decreased GM1 levels.•B3GALT4 siRNA enhanced toxic response to low level MPP+.•Decreased B3GALT4 and GM1 expression increases cell vulnerability to toxic stressors.
Prioritizing conservation interventions based on their cost‐effectiveness may enhance global conservation impact. To do this prioritization, conservation decision‐makers need evidence of what works ...where and how much it costs. Yet, the size, representativeness, and strength of the cost‐effectiveness evidence base are unknown. We reviewed conservation cost‐effectiveness studies, exploring the representation of different types of conservation interventions, habitats and locations, and the methods used. Studies were included if they were published in conservation science or related fields before 2017; were peer‐reviewed; reported costs and conservation‐effectiveness or ratios; and were based on empirical data. From an initial search of 13,184 articles, 91 were considered eligible. We found that the number of cost‐effectiveness studies were growing but remain small. Many common conservation interventions were poorly represented, and there were large geographical biases, with few studies in the world's more biodiverse regions. This sparse and patchy evidence may result from challenges faced when conducting cost‐effectiveness analysis. However, some of these challenges are not unique to cost‐effectiveness studies, and others could be overcome through the use of standardized reporting methods. The reward for overcoming these challenges, and strengthening the evidence base, could be a significant and much‐needed improvement in global conservation.
Summary We identified an adolescent young woman with new-onset diabetes. Due to suspicious family history, she underwent genetic testing for common monogenic diabetes (MODY) genes. We discovered that ...she and her father carry a novel variant of uncertain significance in the HNF1A gene. She was successfully transitioned from insulin to a sulfonylurea with excellent glycemic control. Based on her family history and successful response to sulfonylurea, we propose that this is a novel pathogenic variant in HNF1A. This case highlights the utility of genetic testing for MODY, which has the potential to help affected patients control their diabetes without insulin. Learning points HNF1A mutations are a common cause of monogenic diabetes in patients presenting with early-onset diabetes and significant family history. Genetic testing in suspected patients allows for the identification of mutations causing monogenic diabetes. First-degree relatives of the affected individual should be considered for genetic testing. The use of sulfonylurea agents in patients with HNF1A-MODY can reduce dependence on insulin therapy and provide successful glycemic control.
Anatabine is a minor tobacco alkaloid, which is also found in plants of the Solanaceae family and displays a chemical structure similarity with nicotine. We have shown previously that anatabine ...displays some anti-inflammatory properties and reduces microgliosis and tau phosphorylation in a pure mouse model of tauopathy. We therefore investigated the effects of a chronic oral treatment with anatabine in a transgenic mouse model (Tg PS1/APPswe) of Alzheimer's disease (AD) which displays pathological Aβ deposits, neuroinflammation and behavioral deficits. In the elevated plus maze, Tg PS1/APPswe mice exhibited hyperactivity and disinhibition compared to wild-type mice. Six and a half months of chronic oral anatabine treatment, suppressed hyperactivity and disinhibition in Tg PS1/APPswe mice compared to Tg PS1/APPswe receiving regular drinking water. Tg PS1/APPswe mice also elicited profound social interaction and social memory deficits, which were both alleviated by the anatabine treatment. We found that anatabine reduces the activation of STAT3 and NFκB in the vicinity of Aβ deposits in Tg PS1/APPswe mice resulting in a reduction of the expression of some of their target genes including Bace1, iNOS and Cox-2. In addition, a significant reduction in microgliosis and pathological deposition of Aβ was observed in the brain of Tg PS1/APPswe mice treated with anatabine. This is the first study to investigate the impact of chronic anatabine treatment on AD-like pathology and behavior in a transgenic mouse model of AD. Overall, our data show that anatabine reduces β-amyloidosis, neuroinflammation and alleviates some behavioral deficits in Tg PS1/APPswe, supporting further exploration of anatabine as a possible disease modifying agent for the treatment of AD.
A case series to illustrate difficulties faced in diagnosis, management and subsequent therapeutic approach patients presenting with HLH secondary to lymphoma. A retrospective review of patients ...treated for HLH and lymphoma in Clinical Hematology department of a tertiary care hospital in North India, was performed from Jan 2017 to April 2019. Follow up was included till September 2019. Diagnosis of HLH was made using HLH 2004 criteria along with H score. Only patients who fulfilled HLH 2004 criteria were included. Nine patients were treated during above period, three patients with Hodgkins lymphoma, two patients had DLBCL and four patients had T-cell lymphoma. All patients presented with features of HLH and underlying lymphoma was detected on further evaluation. All patients had H score above the cut off value for diagnosis of HLH. Out of 9 patients, 6 received lymphoma directed chemotherapy and 1 was given only steroids, 1 received IVIG with steroids. 1 died early, before institution of therapy. Out of the 6 patients who received chemotherapy, all attained remission status but two patients had early relapse. In the remaining 3 patients who could not be started on chemotherapy, all died within 3 weeks of presentation. Underlying lymphoreticular malignancy should be actively searched in adult patients presenting with HLH. Early diagnosis and initiation of disease specific therapy with or without specific HLH directed treatment can improve the historical poor prognosis.
Wolfram syndrome (WFS) is an autosomal recessive disorder associated with juvenile-onset diabetes mellitus, optic atrophy, diabetes insipidus, and sensorineural hearing loss. We sought to elucidate ...the relationship between genotypic and phenotypic presentations of Wolfram syndrome which would assist clinicians in classifying the severity and prognosis of Wolfram syndrome more accurately.
Patient data from the Washington University International Registry and Clinical Study for Wolfram Syndrome and patient case reports were analyzed to select for patients with two recessive mutations in the WFS1 gene. Mutations were classified as being either nonsense/frameshift variants or missense/in-frame insertion/deletion variants. Missense/in-frame variants were further classified as transmembrane or non-transmembrane based on whether they affected amino acid residues predicted to be in transmembrane domains of WFS1. Statistical analysis was performed using Wilcoxon rank-sum tests with multiple test adjustment applied via the Bonferonni correction.
A greater number of genotype variants correlated with earlier onset and a more severe presentation of Wolfram syndrome. Secondly, non-sense and frameshift variants had more severe phenotypic presentations than missense variants, as evidenced by diabetes mellitus and optic atrophy emerging significantly earlier in patients with two nonsense/frameshift variants compared with zero or one nonsense/frameshift variants. In addition, the number of transmembrane in-frame variants demonstrated a statistically significant dose-effect on age of onset of diabetes mellitus and optic atrophy among patients with either one or two in-frame variants.
The results contribute to our current understanding of the genotype-phenotype relationship of Wolfram syndrome, suggesting that alterations in coding sequences result in significant changes in the presentation and severity of Wolfram. The impact of these findings is significant, as the results will aid clinicians in predicting more accurate prognoses and pave the way for personalized treatments for Wolfram syndrome.
We assess the magnitude and the extent of recent change of significant human footprint within protected areas, key biodiversity areas and the habitat range of 308 lowland forest specialist birds in ...Sundaland, a global hotspot of biodiversity in Southeast Asia. Using the most recent human footprint dataset, we find that 70% of Sundaland has been heavily modified by humans. This represents a 55% increase in areas under intense human pressure since 1993. Areas under intense human pressure covered on average 50% of the extent of key biodiversity areas, 78% of each protected area and 38% of the range of lowland forest specialist birds. The results imply that the actual level of protection by protected areas is only one‐third to half of that on paper once human footprint is accounted for. While all protected areas were impacted by human pressures, those managed strictly for biodiversity conservation presented the largest increases. These results highlight an exceptionally high human footprint across Sundaland and an impending further deepening of the biodiversity crisis across the region.
PDF
