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Learning outcomes: At the end of the case discussion, students should be able to:▪ analyse and discuss networks as a form of social capital;▪ identify and discuss alternative growth strategies for an small, medium, micro enterprise (SMME) in the context of prevailing challenges;▪ use the six domains of the entrepreneurship ecosystem to identify and discuss factors that enhance and challenge a business with particular reference to an SMME;and▪ analyse and understand the key dimensions of entrepreneurial behaviour using the case protagonist as an example. Case overview/synopsis: Nhlanhla Dlamini, the managing director of Maneli Pets based in Johannesburg, South Africa had opened an office in Cincinnati in the USA in July 2019 to take over the distribution and marketing of the company's high-quality protein pet treats. Just over eight months later, the COVID-19 pandemic exploded across the world resulting in unprecedented disruption to people's lives, world trade and the global economy.Now, in June 2022, Dlamini contemplated the successes and challenges he had experienced since starting Maneli Pets in 2016, not least of which was parting company with US-based Novel Dog LLC, which had previously marketed and distributed the pet treats. He had built an internationally accredited factory from scratch, produced pet products and a brand that was appealing to the competitive international market, and exported to 12 countries around the world. However, Dlamini had also faced the retrenchment of a large number of staff, the breakdown of the relationship with Novel Dog, the difficulties of setting up a distribution business in the USA along with overseeing the South African factory, and in September 2019, his co-founder, Sipha Ndawonde, had left Maneli Pets.Maneli Pets had served Dlamini's philanthropic purpose of creating jobs and contributing to the growth of the South African economy. Despite the setback of parting ways with Novel Dog, he hoped to continue to create jobs and return to and exceed the staff numbers he had achieved by 2018, regardless of the hard work involved.In his dual position of managing director of Maneli Pets, based in Johannesburg, and sales director of the distribution and marketing arm, Nandi Pets Inc. in Cincinnati, Dlamini had a global view of the companies' financials that he realised had been missing initially. Would the new structure of Maneli Pets he had created in 2019 in a pre-pandemic world see the company profitable by the end of 2022? What else could he do to take the company to the next level? Complexity academic level: MBA, Masters in Management, Postgraduate Diploma in Business, Executive Education short courses. Supplementary materials: Teaching notes are available for educators only. Subject code: CSS 3: Entrepreneurship. © 2023, Emerald Publishing Limited.
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Learning outcomes: The learning outcomes focus on enabling students to view operational model changes critically, as they pertain to: ■ evaluating different management styles and uses of the ADKAR change management model in decision-making moments in times of crisis (such as COVID-19) in non-profit organisations (NPOs);■ evaluating different ways in which NPOs pivot to sustainability, including the use of social enterprise models and change management;■ anticipating and managing change in institutional formations through new technologies;■ articulating trade-offs between grant and non-grant resource mobilisation for African philanthropy;and ■ application of change management theory to organisations' sustainability journeys. Case overview/synopsis: In May 2020, working from her home office just over one month into a nationwide lockdown because of the COVID-19 pandemic, Masego Madzwamuse, chief executive officer (CEO) of the Southern Africa Trust (the Trust), knew that it could once again be at a crossroads. In 2015, the Trust had found itself in a quandary when its primary donor gave notification of its intention to withdraw its funding. The Trust had responded by making changes to its structure and strategy. Now, with uncertainty rife throughout South Africa, the CEO knew that she had to consider whether the changes that had been implemented over the past five years had prepared the Trust not only to respond to, but also to survive the pandemic and continue its vital work long into the future. Complexity academic level: Postgraduate Diploma in Management, MBA, Masters in Management. Supplementary materials: Teaching notes are available for educators only. Subject code: CSS 11: Strategy. © 2023, Emerald Publishing Limited.
ABSTRACT
Learning outcomes: At the end of the case discussion, students should be able to:▪ analyse and discuss networks as a form of social capital;▪ identify and discuss alternative growth strategies for an small, medium, micro enterprise (SMME) in the context of prevailing challenges;▪ use the six domains of the entrepreneurship ecosystem to identify and discuss factors that enhance and challenge a business with particular reference to an SMME;and▪ analyse and understand the key dimensions of entrepreneurial behaviour using the case protagonist as an example. Case overview/synopsis: Nhlanhla Dlamini, the managing director of Maneli Pets based in Johannesburg, South Africa had opened an office in Cincinnati in the USA in July 2019 to take over the distribution and marketing of the company's high-quality protein pet treats. Just over eight months later, the COVID-19 pandemic exploded across the world resulting in unprecedented disruption to people's lives, world trade and the global economy.Now, in June 2022, Dlamini contemplated the successes and challenges he had experienced since starting Maneli Pets in 2016, not least of which was parting company with US-based Novel Dog LLC, which had previously marketed and distributed the pet treats. He had built an internationally accredited factory from scratch, produced pet products and a brand that was appealing to the competitive international market, and exported to 12 countries around the world. However, Dlamini had also faced the retrenchment of a large number of staff, the breakdown of the relationship with Novel Dog, the difficulties of setting up a distribution business in the USA along with overseeing the South African factory, and in September 2019, his co-founder, Sipha Ndawonde, had left Maneli Pets.Maneli Pets had served Dlamini's philanthropic purpose of creating jobs and contributing to the growth of the South African economy. Despite the setback of parting ways with Novel Dog, he hoped to continue to create jobs and return to and exceed the staff numbers he had achieved by 2018, regardless of the hard work involved.In his dual position of managing director of Maneli Pets, based in Johannesburg, and sales director of the distribution and marketing arm, Nandi Pets Inc. in Cincinnati, Dlamini had a global view of the companies' financials that he realised had been missing initially. Would the new structure of Maneli Pets he had created in 2019 in a pre-pandemic world see the company profitable by the end of 2022? What else could he do to take the company to the next level? Complexity academic level: MBA, Masters in Management, Postgraduate Diploma in Business, Executive Education short courses. Supplementary materials: Teaching notes are available for educators only. Subject code: CSS 3: Entrepreneurship. © 2023, Emerald Publishing Limited.
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Background: TGF-beta signaling plays an essential role in tissue fibrosis and mediates profibrotic programs after SARS-CoV-2 infection in the kidney and lung. SARS-CoV-2 also induces humoral immune responses controlled by cytokines, including TGF-beta. Studies have found that the incidence of SARS-CoV-2 infection and the severity of Covid-19 in cystic fibrosis (CF) patients is lower than the general population. We studied how SARS-CoV-2 regulates TGF-beta-mediated gene expression in the CF airway. Method(s): Small RNAseq was performed in human bronchial epithelial cells CFBE41o-from a patient homozygous for the F508del mutation in the CFTR gene on Illumina NextSeq 500's. Pathway analysis was done by Ingenuity Pathway Analysis (IPA) software (QIAGEN) and miRNet browser. IPA was used for analyzing coronavirus associated pathways affected by differentially regulated miRNAs. miRNAs predicted to target the coronavirus associated genes were collected from TargetScan Human release 7.2, miRmap, Diana-TarBase v.8, and miRBase bioinformatics tools. Anti-miRNA oligonucleotide miRCURY LNATM Power Inhibitors or control (Exiqon) were used. Cells expressing F508del or wild type CFTR were used to compare the results in CF and non-CF models. Findings were validated in primary human bronchial epithelial (HBE) cells. Result(s): Compared to vehicle control, TGF-beta1 dysregulated 48 miRNAs;38 and 19 pathways were uniquely affected by the upregulated and downregulated miRNAs, respectively. We found 43 miRNAs targeting 119 different mRNA of the proteins associated with coronavirus pathogenesis pathway and 21 miRNAs targeting 21 different mRNA of the proteins associated with coronavirus replication pathway. Two miRNAs upregulated by TGF-beta1 target the host receptor for SARS-CoV-2 invasion, angiotensin converting enzyme 2 (ACE2). We confirmed the results by qRT-PCR that TGF-beta1 increased expression of specific miRNAs targeting ACE2 mRNA. Upregulation of the miRNAs was followed by inhibition of ACE2 mRNA and protein levels and the effect was blocked by specific anti-miRNA oligonucleotides. The above results differed between the CF and non-CF cells. Conclusion(s): miRNAs may be important effectors of TGF-beta modulating SARSCoV-2 pathogenicity and replication in the CF airway. Ongoing studies focus on elucidating the mechanisms of SARS-CoV-2 invasion of kidney cells.
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Symbiotic interaction between the human body and its microbiota is an important issue of modern biomedicine and personalized medicine. However, little is known on molecular mechanisms of that relationship. Bearing in mind the ubiquitous participation of peptides in biomolecular interactions and regulatory processes we attempted direct search of blood peptides originated from microbial proteins. LC-MS/MS analysis was carried out of blood serum and plasma samples taken from 20 healthy donors on Q Exactive HF-X Hybrid Quadrupole-Orbitrap mass-spectrometer. Sample preparation was carried out based on our previously developed method of peptide desorption from the surface of major blood plasma proteins followed by standard chromatographic steps. Human microbiota protein sequences were taken from NIH Human Microbiome Project. As a result, out of 13,625 identified peptides 912 were unique fragments of microbial precursors, which is about 6.69% of the total amount of detected bloodstream peptides. In 30 cases peptide identification was confirmed by mass-spectral study of individual synthetic samples. Absolute quantification by the mass-spectrometric method of multiple reaction monitoring (MRM) confirmed the presence of bacterial peptides in plasma and serum in the range of approximately 0.1 nM to 1 uM, which is comparable to physiologically significant hormone concentrations in human blood in normal conditions. The abundance of microbiota peptides reaches its maximum 5h after a meal. Most of the peptides correlate with the bacterial composition of the small intestine and are likely obtained by hydrolysis of membrane proteins with trypsin, chymotrypsin and pepsin - the main proteases of the gastrointestinal tract. The isolated fraction of peripheral blood mononuclear cells showed increase secretion of proinflammatory cytokines, colony stimulating factors and chemoattractants as the response to the addition of some of the identified microbiotic peptides. Such peptides - identified both in the plasma and in the serum - have properties of resistance to fibrinolysis, since the pool of peptides is preserved after passing through the digestive tract. The physicochemical properties of the identified bacterial peptides are consistent with those required for the selective permeability of mucosal barriers. Our approach to the identification of microbiota peptides in the blood serum and plasma may be useful for determining the microbiota composition of hard-to-reach intestinal areas, such as the small intestine, and for monitoring the permeability of the intestinal mucosal barrier.
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Symbiotic interaction between the human body and its microbiota is an important issue of modern biomedicine and personalized medicine. However, little is known on molecular mechanisms of that relationship. Bearing in mind the ubiquitous participation of peptides in biomolecular interactions and regulatory processes we attempted direct search of blood peptides originated from microbial proteins. LC-MS/MS analysis was carried out of blood serum and plasma samples taken from 20 healthy donors on Q Exactive HF-X Hybrid Quadrupole-Orbitrap mass-spectrometer. Sample preparation was carried out based on our previously developed method of peptide desorption from the surface of major blood plasma proteins followed by standard chromatographic steps. Mascot and X! Tandem search engines were used for peptide identification. Human protein sequences were taken from UniProt Knowledgebase and sequences of human microbiota proteins-from NIH Human Microbiome Project (HMP). As a result, out of 13625 identified peptides 912 were unique fragments of microbial precursors, which is 6.69% of the total amount of detected bloodstream peptides. In 30 cases peptide identification was confirmed by mass-spectral study of individual synthetic samples. Absolute quantification by the mass-spectrometric method of multiple reaction monitoring (MRM) confirmed the presence of bacterial peptides in plasma and serum in the range of approximately 0.1 nMol/L to 1 mkMol/L, which is comparable to physiologically significant hormone concentrations in human blood in normal conditions. Analysis of the in silico obtained hydrolyzates of microbiotic proteins showed that significant number of the identified peptides are derived from the precursor proteins as a result of hydrolysis with trypsin, chymotrypsin and pepsin, the main proteases of the gastrointestinal system. 60% of the identified “microbial” peptides are derived from the intestine flora, about 20% - from oral microbiota and 20% fall on the remaining microbiotic communities. Most of the precursor proteins refer to intracellular, cytoplasmic proteins. The isolated fraction of peripheral blood mononuclear cells showed increase secretion of proinflammatory cytokines, colony stimulating factors and chemoattractants as the response to the addition of some of the identified microbiotic peptides. The data obtained serve as a basis for the ongoing study of the functional properties of microbiome derived peptides.
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Objective: The ARRIVE Trial (2018) has potentially changed the practice of scheduling elective inductions of labor. Our goal was to demonstrate how the publication of the trial impacted one tertiary care center’s practice of scheduling elective inductions and affected the resulting labor outcomes. Study Design: We conducted a retrospective cohort study obtaining information about the births at an academic tertiary care center during the 18-month period prior to publication of the ARRIVE Trial (Feb 1 2017 - Aug 1 2018) and the 18 months after publication (Sep 1 2018 - Mar 1 2020) and before the lockdown necessitated by the COVID-19 pandemic. We included women ≥18 years with elective inductions between 39 and 41 weeks gestation, defined as having no medical indication for induction. Chi-squared tests and two sample t-tests were used for comparison of group characteristics and birth outcomes before and after trial publication. Results: A total of 3213 births were included, with 1542 from the pre-ARRIVE period and 1671 from post-ARRIVE. The rate of elective inductions increased from 9.9% of total births pre-ARRIVE to 27.4% of births post-ARRIVE for a 2.8 times increase. After the trial publication, elective inductions occurred at an earlier gestational age (p < 0.001) and among women who were slightly younger (p=0.03), had higher BMI (p=0.002), and lower parity (p < 0.001) on average. The rate of cesarean delivery among electively induced women increased from 6.5% pre-ARRIVE to 14.8% post-ARRIVE (p=0.01). The post-ARRIVE cohort also had longer hospital stays (p=0.002), increased blood loss (p=0.001), and lower birth weights (p=0.005). Conclusion: The publication of the ARRIVE trial significantly impacted the scheduling of elective inductions at our institution, resulting in more than a twofold increase. After publication, elective inductions were performed earlier and resulted in a higher rate of unscheduled cesarean deliveries and other adverse labor outcomes. [Formula presented] [Formula presented]
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Objective: The start of quarantine for the COVID-19 pandemic in March 2020 began a prolonged period of isolation from family and crucial social support for many pregnant and postpartum patients throughout the country. The objective of this study was to compare the score of the Edinburgh Postnatal Depression Scale (EPDS), breastfeeding, and compliance with postpartum gestational diabetes follow-up in cohorts before and after the beginning of the COVID-19 pandemic. Study Design: This was a historical cohort study of women presenting for postpartum care in March through May of 2019 and 2020 at a tertiary academic medical center. Demographic information, parity, delivery routes, EPDS scores, maternal mental health history, partner status, and postpartum diabetes screening completion were ed from the electronic medical record. Results were compared between the 2019 and 2020 cohorts. Results: There were 579 women with postpartum visits in the study timeframe, with 260 in 2019 and 319 in 2020. Age, gestational age at delivery, pre-gravid BMI, and partner status were similar between cohorts. (Table 1) There was no difference in history of a mental health diagnosis, history of mental health medication use, or mental health treatment during pregnancy between cohorts. There were more nulliparous patients, cesarean deliveries, African American patients, and Asian patients in 2020. The mean EPDS score was similar between cohorts;there was no difference in breastfeeding or 2-hour glucose tolerance test compliance in women who had gestational diabetes. (Table 2) There was a non-significant trend toward more new postpartum depression treatment in 2020. Conclusion: In our population, the start of the COVID-19 pandemic and resulting social disruption was not associated with a difference between EPDS scores, breastfeeding, completion of gestational diabetes follow up or incidence of initiation of mental health treatment in the postpartum period in our population. [Formula presented] [Formula presented]
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Recently developed COVID-19 vaccines significantly reduce the risk of severe coronavirus disease, which is essential in the particularly vulnerable cancer patient population. There is a growing anti-vaccine concern that may affect the success of the fight against the SARS-CoV2 pandemic. To evaluate opinions and attitudes toward vaccination, we conducted an anonymous online survey among Polish patients diagnosed with cancer. We analyzed how socio-demographic factors, type of cancer, comorbidities, previous influenza vaccinations, and information sources affect the general willingness and opinions about vaccinations, emphasizing vaccination against COVID-19. Six hundred thirty-five patients (80.2% female) participated in the study. A positive attitude towards vaccination was presented by 73.7%, neutral by 17.8%, while negative by 8.5%. Willingness to get vaccinated was declared by 60.3%, 23.5% were unwilling, and 16.2% were undecided. Significant predictors of willingness were education, marital status, active anti-cancer treatment, previous influenza vaccination, and positive attitude towards vaccinations. Patients with cancer have concerns regarding safety, effectiveness, and the process of development of the COVID-19 vaccine. Overall, patients with cancer present positive attitudes towards COVID-19 vaccination but required sufficient information on its efficacy and side effects.
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Many detection methods have been used or reported for the diagnosis and/or surveillance of COVID-19. Amongthem, reverse transcription polymerase chain reaction (RT-PCR) is the most commonly used because of its highsensitivity, typically claiming detection of about 5 copies of viruses. However, it has been reported that only 47-59%of the positive cases were identified by some RT-PCR methods, probably due to low viral load, timing of sampling, degradation of virus RNA in the sampling process, or possible mutations spanning the primer binding sites.Therefore, alternative and highly sensitive methods are imperative. With the goal of improving sensitivity andaccommodating various application settings, we developed a multiplex-PCR-based method comprising 343 pairs ofspecific primers and demonstrated its efficiency at detecting SARS-CoV-2 at low copy numbers. The assayproduced clean characteristic target peaks of defined sizes, which allowed for direct identification of positives byelectrophoresis. We further amplified the entire SARS-CoV-2 genome from 8 to half a million viral copies purifiedfrom 13 COVID-19 positive specimens and detected mutations through next-generation sequencing. Finally, wedeveloped a multiplex-PCR-based metagenomic method in parallel that required modest sequencing depth foruncovering SARS-CoV-2 mutational diversity and potentially novel or emerging isolates..