The impact of phenotype, ethnicity and genotype on progression of Type 2 diabetes mellitus

Aim: To conduct a comprehensive review of studies of glycaemic deterioration in type 2 diabetes and identify the major factors influencing progression.Methods: We conducted a systematic literature search with terms linked to type 2 diabetes progression. All the included studies were summarized based upon the factors associated with diabetes progression and how the diabetes progression was defined.Results: Our search yielded 2785 articles; based on title, abstract and full‐text review, we included 61 studies in the review. We identified seven criteria for diabetes progression: ‘Initiation of insulin’, ‘Initiation of oral antidiabetic drug’, ‘treatment intensification’, ‘antidiabetic therapy failure’, ‘glycaemic deterioration’, ‘decline in beta‐cell function’ and ‘change in insulin dose’. The determinants of diabetes progression were grouped into phenotypic, ethnicity and genotypic factors. Younger age, poorer glycaemia and higher body mass index at diabetes diagnosis were the main phenotypic factors associated with rapid progression. The effect of genotypic factors on progression was assessed using polygenic risk scores (PRS); a PRS constructed from the genetic variants linked to insulin resistance was associated with rapid glycaemic deterioration. The evidence of impact of ethnicity on progression was inconclusive due to the small number of multi‐ethnic studies.Conclusion: We have identified the major determinants of diabetes progression—younger age, higher BMI, higher HbA1c and genetic insulin resistance. The impact of ethnicity is uncertain; there is a clear need for more large‐scale studies of diabetes progression in different ethnic groups

Toll-like Receptor 4 (TLR4) in Acute and Chronic Renal Diseases

Despite advances in its treatment, the incidence of renal diseases has been consistently increasing. Hence, there is a need to understand the underlying molecular mechanisms of the progression of kidney diseases. Recent research implicates inflammation as an important mediator of renal injury. We hypothesized that inhibiting Toll-like receptor 4 (TLR4), an upstream modulator of several inflammatory pathways, would prevent the progression of renal diseases. First, we determined the mechanism by which AngiotensinII (AngII)-induced inflammation is modulated by TLR4 using an in vitro model of rat tubulo-epithelial cells. We blocked TLR4 using gene silencing strategy in NRK52E cells. In TLR4-silenced cells, the expression of TLR4 was decreased, activation of NF-κB was reduced, inflammation and oxidative stress were attenuated, suggesting a role for TLR4 in potentiating AngII-induced renal inflammation. We then focused on an in vivo acute kidney injury (AKI) model to elucidate the effect of TLR4 in AKI. We used lipopolysaccharide (LPS), a specific ligand of TLR4, to induce AKI. We injected one group of rats with VIPER, a TLR4 inhibitory peptide, before LPS administration. We also used blueberry as a non-pharmacological approach to study if blueberry could protect against LPS-induced AKI. Compared to LPS-administered rats, the BB-pretreated animals exhibited improved renal hemodynamics, attenuated expression of TLR4 and inflammation. The results in the BB-pretreated group were consistent with the VIPER-treated rats. This indicates that TLR4 is an important mediator in LPS-induced AKI, and suggest that BB, by inhibiting TLR4, is a viable non-pharmacological option to decrease AKI. We also examined the effect of TLR4 signaling and its downstream mechanism in an animal model of metabolic syndrome-associated chronic kidney disease (CKD) and investigated if a blueberry-enriched diet could attenuate the progression of CKD. We showed that OZR exhibited lower glucose tolerance, exacerbated renal dysfunction and increased oxidative stress. Expression levels of TLR4 and, phosphorylation of ERK and p38MAPK were higher. This was accompanied by increased renal pathology. BB-fed OZR showed significant improvements in all of these parameters. This suggests that the TLR4-MAPK signaling pathway is a key to the renal dysfunction in MetS, and BB protects against this damage by inhibiting TLR4

Advances on the Resilience of Complex Networks

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ISO 9000 Internalization and Organizational Commitment - Implications for Process Improvement and Operational Performance

This study presents an investigation of the relationship between internalization of ISO 9000 practices and the development of intellectual capital within organizations. We posit that intellectual capital, which comprises of human capital, organizational capital, and social capital, leads to improved processes in an organization. Process improvement, in turn, results in superior operational performance. Using a sample of 321 ISO 9001 certified organizations, the hypothesized relationships are tested by means of the structural equation modeling technique. The results of this study lend strong support for the hypotheses and show that performance benefits from the internalization of ISO 9000 standards occur mainly through the development of human and organizational capital, and the consequent improvement in business processes. This study discusses theoretical and managerial implications, and presents directions for future research

ISO 9000 Internalization and Organizational Commitment - Implications for Process Improvement and Operational Performance

This study presents an investigation of the relationship between internalization of ISO 9000 practices and the development of intellectual capital within organizations. We posit that intellectual capital, which comprises of human capital, organizational capital, and social capital, leads to improved processes in an organization. Process improvement, in turn, results in superior operational performance. Using a sample of 321 ISO 9001 certified organizations, the hypothesized relationships are tested by means of the structural equation modeling technique. The results of this study lend strong support for the hypotheses and show that performance benefits from the internalization of ISO 9000 standards occur mainly through the development of human and organizational capital, and the consequent improvement in business processes. This study discusses theoretical and managerial implications, and presents directions for future research

Closed atraumatic flexor hallucis longus tendon rupture following hallux valgus correction repaired using a turn down flap

A case report of closed atraumatic rupture of flexor hallucis longus (FHL) tendon few months after hallux valgus correction in a high functioning individual is presented. There have been only two cases of FHL tendon rupture reported following hallux valgus correction in literature till now. Our patient underwent Hallux valgus corrective osteotomy, 4 months after which he presented with rupture of the FHL tendon, he subsequently underwent successful surgical turn down flap repair with good clinical outcome. Closed atraumatic rupture of FHL tendon as an isolated injury is a rare event evidenced by systematic review reporting only 10 cases in literature till now. Low clinical suspicion of FHL rupture in closed foot injuries could be one factor resulting in fewer cases being reported in literature. Acute rupture of FHL tendon following open foot injuries and partial closed rupture due to tendinitis in dancers have been reported frequently in literature. In conclusion, we emphasize careful handling of FHL tendon while performing corrective osteotomy of the hallux in any patient. Although, turn down flap is a well-documented technique to bridge gaps and repair chronic tendo-achilles rupture, we were able to replicate the same technique in our patient and produce good functional result using this effective tendon repair technique to bridge segmental gap as evidence by return of almost normal power of great toe plantar flexion

The effect of customers’ unethical practices on suppliers’ intention to continue their relationships

This study examines inter-firm buyer–supplier relationships through an ethical lens. Drawing on the concept of reciprocity in social exchange theory as well as resource dependence theory, we examine the effect of customers’ unethical practices on their suppliers’ intention to continue their business relationships with their customers. Specifically, we distinguish two types of unethical practices: unfair business practices, which directly target suppliers and socially irresponsible practices, which have an impact on wider society. Integrating social exchange theory and resource dependence theory, we investigate the effects of two moderating factors: suppliers’ dependence on their customers and the benefits derived from the supplier–customer relationship. Using data obtained from 506 managers from small-to-medium-sized firms, our findings show that both customers’ unfair business practices and socially irresponsible practices have negative relationships with their suppliers’ intention to continue the relationships. These effects are moderated by supplier dependence and benefits derived from their customers. Overall, our study shows that intention to continue in these relationships, in response to unethical practices by customers, is bounded by supplier self-interest and resource dependence. Our study is one of the few to examine suppliers’ responses to unethical practices and our findings are consistent with the notion of weak reciprocity, rather than strong reciprocity that predominates in the literature.</p

Severe Degloving Injury with Covid-19 Infection – Successful Outcome and Hard Lessons Learnt

&nbsp;Here we share an interesting case of severe trauma with tissue loss to nearly half of the back and a lacerated perineum in a Covid-19 positive patient in septic shock. This article highlights our experiences and hard lessons learnt in successful management of this complicated injury. Managing severe trauma is a challenge especially with respiratory failure resulting from Covid-19 infection. The patient reported to the hospital during a very difficult period, when proper medical care was difficult as hospitals and wards were filled with Covid positive patients. Managing patients was difficult especially wearing personal protective equipment round the clock. It’s a challenge when an entire team of surgeon, anesthesiologist, nursing staff and paramedics, rose above their daily call of duty to save the patient for her children. It was a fight against time and an many unknown enemy over three months for the entire team. The challenge to save a middle-aged patient from the claws of death against all odds was really miraculous. It was highly rewarding to see the patient going back to the family with a smile