The Interrelated Multifactorial Actions of Cortisol and Klotho: Potential Implications in the Pathogenesis of Parkinson's Disease.

The pathogenesis of Parkinson's disease (PD) is complex, multilayered, and not fully understood, resulting in a lack of effective disease-modifying treatments for this prevalent neurodegenerative condition. Symptoms of PD are heterogenous, including motor impairment as well as non-motor symptoms such as depression, cognitive impairment, and circadian disruption. Aging and stress are important risk factors for PD, leading us to explore pathways that may either accelerate or protect against cellular aging and the detrimental effects of stress. Cortisol is a much-studied hormone that can disrupt mitochondrial function and increase oxidative stress and neuroinflammation, which are recognized as key underlying disease mechanisms in PD. The more recently discovered klotho protein, considered a general aging-suppressor, has a similarly wide range of actions but in the opposite direction to cortisol: promoting mitochondrial function while reducing oxidative stress and inflammation. Both hormones also converge on pathways of vitamin D metabolism and insulin resistance, also implicated to play a role in PD. Interestingly, aging, stress and PD associate with an increase in cortisol and decrease in klotho, while physical exercise and certain genetic variations lead to a decrease in cortisol response and increased klotho. Here, we review the interrelated opposite actions of cortisol and klotho in the pathogenesis of PD. Together they impact powerful and divergent mechanisms that may go on to influence PD-related symptoms. Better understanding of these hormones in PD would facilitate the design of effective interventions that can simultaneously impact the multiple systems involved in the pathogenesis of PD

Dysfunctional uterine bleeding: ormeloxifene versus combined oral contraceptive pills

Background: Dysfunctional uterine bleeding is abnormal bleeding that occurs in the absence of recognizable pelvic pathology, general medical disease, or pregnancy.  Globally, health care systems are focusing on low morbidity and low cost therapeutic interventions. Hence, medical treatment for DUB is high on the priority list. This comparative study was conducted to analyse the efficacy of ormeloxifene and combined oral contraceptive pills in reducing the blood loss and endometrial thickness in cases of DUB.Methods: This prospective study was conducted on women with dysfunctional uterine bleeding, who attended Gynaecology OPD at Hind Institute of Medical Sciences, between August 2015 and April 2016. After applying inclusion and exclusion criteria, 72 women diagnosed with DUB were enrolled randomly in two groups A and B. Group A was treated by Ormeloxifene and Group B patients were treated with combined oral contraceptive pills for three consecutive cycles. The efficacies of the studied drugs were compared by analyzing the mean change in the pre and post treatment PBAC score, haemoglobin level and endometrial thickness using unpaired t-test.Results: Ormeloxifene was found to be significantly more effective (p <0.0001) than OCPs in controlling the menstrual blood loss (79% reduction in group A Vs 55.5% reduction in group B). Reduction in endometrial thickness was also more in the group receiving Ormrloxifene, however this was statistically not significant (p = 0.19). No major side effect observed with the use of Ormeloxifene.Conclusions: Ormeloxifene can be an effective and safe therapy in the treatment of Dysfunctional uterine bleeding

In vivo imaging of cellular proliferation in colorectal cancer using positron emission tomography

Background and aims: Positron emission tomography (PET) using 18F labelled 2-fluoro-2-deoxy-D-glucose (18FDG) is an established imaging tool, although the recent development of a biologically stable thymidine analogue [18F] 3'-deoxy-3-fluorothymidine (18FLT) has allowed PET to image cellular proliferation by utilising the salvage pathway of DNA synthesis. In this study, we have compared uptake of 18FLT and 18FDG with MIB-1 immunohistochemistry to evaluate the role of PET in quantifying in vivo cellular proliferation in colorectal cancer (CRC). Patients and methods: Patients with resectable, primary, or recurrent CRC were prospectively studied. Thirteen lesions from 10 patients (five males, five females), median age 68 years (range 54–87), were evaluated. Patients underwent 18FDG and 18FLT PET scanning. Tracer uptake within lesions was quantified using standardised uptake values (SUVs). Histopathological examination and MIB-1 immunohistochemistry were performed on all lesions, and proliferation quantified by calculating a labelling index (% of MIB-1 positively stained nuclei within 1500 tumour cells). Results: Histology confirmed adenocarcinoma in 12 of 13 lesions; the remaining lesion was reactive. All eight extrahepatic lesions were visualised using both 18FLT and 18FDG. Three of the five resected liver metastases were also avid for 18FLT and showed high proliferation, while the remaining two lesions which demonstrated no uptake of 18FLT had correspondingly very low proliferation. There was a statistically significant positive correlation (r =0.8, p<0.01) between SUVs of the tumours visualised with 18FLT and the corresponding MIB-1 labelling indices. No such correlation was demonstrated with 18FDG avid lesions (r =0.4). Conclusions: 18FLT PET correlates with cellular proliferation markers in both primary and metastatic CRC. This technique could provide a mechanism for in vivo grading of malignancy and early prediction of response to adjuvant chemotherapy

Double-minute chromosomes in the leukocytes of a patient with a previous history of cervical carcinoma

Double-minute chromosomes (DMs) were observed in repeated samples in the leukocytes of a patient with a previous history of cervical carcinoma. The most interesting cytogenetic finding was the coexistence of DMs and a dicentric chromosome along with chromosome- and chromatid-type breaks and gaps. This observation suggests that DMs might originate through the breakage of existing chromosomes. The presence of DMs in leukocytes may also indicate the possibility that certain common agents cause DMs in tumor cells as well as in normal cells

Achieving Circularity is a Distant Dream: Entrepreneurial Barriers to Circular Business Models in SMEs of Emerging Economies

Purpose: Circularity has acted as an essential phenomenon for Small and Medium Enterprises (SMEs) in emerging economies, pressuring entrepreneurs to its adoption in their businesses. During the adoption and implementation of circularity, entrepreneurs or circular entrepreneurs (to be precise) are facing various challenges to its effective functioning. However, the scholarly literature has offered limited research into this phenomenon. Thus, the purpose of this research is to identify the various barriers and sub-barriers for circular entrepreneurs to adopt circularity in SMEs of emerging economies. Design/methodology/approach: A combined qualitative and quantitative approach was employed to achieve the objectives of the study. In the first stage, through an extensive literature review, a list of barriers was identified and in the second stage, a deductive approach was employed to finalize the barriers. Finally, Best-Worst Method (BWM), a multi-criteria decision-making (MCDM) method, was used to analyze the significant importance of the barriers. Findings: The findings of the study suggested the ‘financial barrier’ as the first-ranked barrier in the adoption of Circular Business Models (CBMs), followed by the ‘regulatory and operational barriers’ as the top second and third barriers. In terms of sub-barriers, ‘lack of access to funding and capital’ has been identified as the top sub-barrier in the adoption of CBM, followed by ‘excessive regulations and red tape’ and ‘challenges due to ambiguity of the concept’. Practical implications: To transition from a circular to a linear business approach considerably quicker and smoother, entrepreneurs may utilize the findings of this study as a blueprint for the steps to overcome the barriers in a linear to a circular transition. Originality: This research differentiates from other studies due it solicited input directly from the people who are most familiar with the challenges of making the transition from linear to CBM, i.e. the entrepreneurs themselves

Achieving the Sustainable Development Goals through Net Zero Emissions: Innovation-Driven Strategies for Transitioning from Incremental to Radical Lean, Green and Digital Technologies

This work adopts a resource-based view for strategically managing firms’ tangible and intangible resources based on lean and green philosophies to explore the role of digital technologies in achieving NZE and the SDGs.This research outlines three contemporary issues. First, it assesses the theory-driven approaches and real-world datasets from conference of parties (COP) meetings. Second, adopting the VRIO (Valuable, Rare, Inimitable, Organized) framework, 25 identified digital technology-based values are obtained by digitalization-based integrated lean-green approaches that may enable manufacturing firms to pursue SDGs via net-zero emissions. Four scenarios of digital technology adoption and integration level of lean and green manufacturing pathways are proposed, differentiated by the degree of radical/ incremental interests in innovation and sustainable advantage types. Third, the study highlights that the achievement of NZE by SDGs may be possible only by adopting digital technologies and high-level integration of lean and green

Can Industry 5.0 Technologies Overcome Supply Chain Disruptions? - A Perspective Study on Pandemics, War, and Climate Change Issues

Industry 5.0 (I5.0) is the next industrial revolution that will leverage human intervention in collaboration with intelligent, logical, and smart machines to attain even more user-preferred and resource-efficient manufacturing and supply chain solutions. The main aim of this article is to study I5.0 technologies in supply chains when these are affected by disruptive phenomena such as those created by wars, climate change or pandemics. A systematic literature review methodology was conducted to understand the present knowledge connected with this theme. This study summarises 194 research articles from the period 2009 to 2022 to understand the present knowledge connected with this theme. The research findings show a significant gap related to the adoption of I5.0 technologies to prevent or overcome supply chain disruptions. 194 articles, including journal and review articles, were identified in the literature. The study provides a novel and insightful concept related to I5.0 within the context of supply chain disruptions. The potential applications of I5.0 and Industry 4.0 are elaborately discussed in three areas, namely: (1) disruptions in supply chains due to pandemics; (2) disruptions in supply chains due to war; and (3) disruptions in supply chains due to climate change. Finally, this study highlights research implications and proposes future research avenues that will contribute to further exploring the adoption of I5.0 technologies to prevent, manage and overcome disruptions in supply chains

Nucleolar organizer regions in patients with precancerous and cancerous lesions of the uterine cervix

Nucleolar organizer regions (Ag-NORs) were studied in patients with cervical precancerous and cancerous lesions along with controls. The data revealed a statistically significant decrease of Ag-NORs in cancer patients, as well as in women with severe precancerous lesions as compared with controls. A similar decrease in the amount of Ag-staining was also observed in both cancer and severe dysplasia cases. The study suggests a possible relationship of Ag-NOR activity to malignancy