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Background Role modelling’s pivotal part in the nurturing of a physician’s professional identity remains poorly understood. To overcome these gaps, this review posits that as part of the mentoring spectrum, role modelling should be considered in tandem with mentoring, supervision, coaching, tutoring and advising. This provides a clinically relevant notion of role modelling whilst its effects upon a physician’s thinking, practice and conduct may be visualised using the Ring Theory of Personhood (RToP). Methods A Systematic Evidence Based Approach guided systematic scoping review was conducted on articles published between 1 January 2000 to 31 December 2021 in the PubMed, Scopus, Cochrane, and ERIC databases. This review focused on the experiences of medical students and physicians in training (learners) given their similar exposure to training environments and practices. Results 12,201 articles were identified, 271 articles were evaluated, and 145 articles were included. Concurrent independent thematic and content analysis revealed five domains: existing theories, definitions, indications, characteristics, and the impact of role modelling upon the four rings of the RToP. This highlights dissonance between the introduced and regnant beliefs and spotlights the influence of the learner’s narratives, cognitive base, clinical insight, contextual considerations and belief system on their ability to detect, address and adapt to role modelling experiences. Conclusion Role modelling’s ability to introduce and integrate beliefs, values and principles into a physician’s belief system underscores its effects upon professional identity formation. Yet, these effects depend on contextual, structural, cultural and organisational influences as well as tutor and learner characteristics and the nature of their learner-tutor relationship. The RToP allows appreciation of these variations on the efficacy of role modelling and may help direct personalised and longitudinal support for learners.

Background Mentoring’s pivotal role in nurturing professional identity formation (PIF) owes much to its combined use with supervision, coaching, tutoring, instruction, and teaching. However the effects of this combination called the ‘mentoring umbrella’ remains poorly understood. This systematic scoping review thus aims to map current understanding. Methods A Systematic Evidence-Based Approach guided systematic scoping review seeks to map current understanding of the ‘mentoring umbrella’ and its effects on PIF on medical students and physicians in training. It is hoped that insights provided will guide structuring, support and oversight of the ‘mentoring umbrella’ in nurturing PIF. Articles published between 2000 and 2021 in PubMed, Scopus, ERIC and the Cochrane databases were scrutinised. The included articles were concurrently summarised and tabulated and concurrently analysed using content and thematic analysis and tabulated. The themes and categories identified were compared with the summaries of the included articles to create accountable and reproducible domains that guide the discussion. Results A total of 12201 abstracts were reviewed, 657 full text articles evaluated, and 207 articles included. The three domains identified were definitions; impact on PIF; and enablers and barriers. The mentoring umbrella shapes PIF in 3 stages and builds a cognitive base of essential knowledge, skills and professional attitudes. The cognitive base informs thinking, conduct and opinions in early supervised clinical exposure in Communities of practice (COP). The COPs’ individualised approach to the inculcation of desired professional characteristics, goals, values, principles and beliefs reshapes the individual’s identity whilst the socialisation process sees to their integration into current identities. Conclusion The mentoring umbrella’s provides personalised longitudinal support in the COP and socialisation process. Understanding it is key to addressing difficulties faced and ensuring holistic and timely support.

Type 2 Diabetes Mellitus (T2DM) is reported to affect one in 11 adults worldwide, with over 80% of T2DM patients residing in low-to-middle-income countries. Health systems play an integral role in responding to this increasing global prevalence, and are key to ensuring effective diabetes management. We conducted a systematic review to examine the health system-level factors influencing T2DM awareness, treatment, adherence, and control. A protocol for this study was published on the PROSPERO international prospective register of systematic reviews (PROSPERO 2016: CRD42016048185). Studies included in this review reported the effects of health systems factors, interventions, policies, or programmes on T2DM control, awareness, treatment, and adherence. The following databases were searched on 22 February 2017: Medline, Embase, Global health, LILACS, Africa-Wide, IMSEAR, IMEMR, and WPRIM. There were no restrictions on date, language, or study designs. Two reviewers independently screened studies for eligibility, extracted the data, and screened for risk of bias. Thereafter, we performed a narrative synthesis. A meta-analysis was not conducted due to methodological heterogeneity across different aspects of included studies. 93 studies were included for qualitative synthesis; 7 were conducted in LMICs. Through this review, we found two key health system barriers to effective T2DM care and management: financial constraints faced by the patient and limited access to health services and medication. We also found three health system factors that facilitate effective T2DM care and management: the use of innovative care models, increased pharmacist involvement in care delivery, and education programmes led by healthcare professionals. This review points to the importance of reducing, or possibly eliminating, out-of-pocket costs for diabetes medication and self-monitoring supplies. It also points to the potential of adopting more innovative and integrated models of care, and the value of task-sharing of care with pharmacists. More studies which identify the effect of health system arrangements on various outcomes, particularly awareness, are needed.

Spinal muscular atrophy (SMA) is typically characterized as a motor neuron disease, but extraneuronal phenotypes are present in almost every organ in severely affected patients and animal models. Extraneuronal phenotypes were previously underappreciated, as patients with severe SMA phenotypes usually died in infancy; however, with current treatments for motor neurons increasing patient lifespan, impaired function of peripheral organs may develop into significant future comorbidities and lead to new treatment-modified phenotypes. Fatty liver is seen in SMA animal models, but generalizability to patients and whether this is due to hepatocyte-intrinsic survival motor neuron (SMN) protein deficiency and/or subsequent to skeletal muscle denervation is unknown. If liver pathology in SMA is SMN dependent and hepatocyte intrinsic, this suggests SMN-repleting therapies must target extraneuronal tissues and motor neurons for optimal patient outcome. Here, we showed that fatty liver is present in SMA patients and that SMA patient-specific induced pluripotent stem cell-derived hepatocyte-like cells were susceptible to steatosis. Using proteomics, functional studies, and CRISPR/Cas9 gene editing, we confirmed that fatty liver in SMA is a primary SMN-dependent hepatocyte-intrinsic liver defect associated with mitochondrial and other hepatic metabolism implications. These pathologies require monitoring and indicate the need for systematic clinical surveillance and additional and/or combinatorial therapies to ensure continued SMA patient health.

Background The current group B streptococcal (GBS) preventive measures had reduced invasive GBS early onset disease (EOD) incidences worldwide, but the late onset disease (LOD) incidences had remained unchanged. Administration of a safe and effective GBS vaccine in addition to the current strategies were thought to be the next steps in reducing the incidences of invasive GBS infection especially LOD. In this study, we aimed to examine the causative GBS serotypes in invasive GBS disease, determine the incidences of EOD and LOD, and compare the risk factors between EOD and LOD. Methods A retrospective study of infants ≤ 90-day-old over an 8-year period (2010–2017). The incidences of EOD and LOD were obtained by using patients with EOD and LOD who were born in our institution as the numerator and the live births in our institution per year of the study period as the denominator. Available GBS isolates were serotyped by the National Public Health Laboratory using capsular serotyping methods. The risk factors of EOD and LOD were compared. Results A total of 71 infants were identified; 16 (22.5%) and 55 (77.5%) of them had EOD and LOD, respectively. Serotype III (n = 42, 71.2%) was the most common serotype amongst the 59 isolates available for serotyping. Serotypes Ia, Ib, II, III, and V accounted for 98.3% (n = 58) of the invasive GBS diseases. The overall incidence was 0.42 per 1000 live births. The mean incidences of EOD and LOD were 0.13 per 1000 live births and 0.29 per 1000 live births, respectively. On multivariate analysis, risk factors for LOD as compared to EOD were: Chinese ethnicity (OR 27.1, 95% CI 3.0–243.1, p = 0.003) and negative/unknown maternal GBS status (OR 20.0, 95% CI 2.0–250.0, p = 0.012). Prematurity and intrapartum risk factors (peripartum maternal pyrexia, prolonged rupture of membrane) of EOD were not associated with LOD. Conclusions The LOD incidence had remained higher than EOD incidence in our cohort. A GBS vaccine that covers the major causative serotypes found in our cohort can potentially reduce the overall GBS disease burden in the country.

Individuals with type 2 diabetes are at increased risk of acquiring melioidosis, a disease caused by Burkholderia pseudomallei infection. Although up to half of melioidosis patients have underlying diabetes, the mechanisms involved in this increased susceptibility are unknown. We found that B. pseudomallei-infected PBMCs from diabetic patients were impaired in IL-12p70 production, which resulted in decreased IFN-γ induction and poor bacterial killing. The defect was specific to the IL-12-IFN-γ axis. Defective IL-12 production was also observed during Mycobacterium tuberculosis infection, in which diabetes is likewise known to be a strong risk factor. In contrast, IL-12 production in diabetic cells was not affected upon Salmonella enterica infection or in response to TLR2, -3, -4, and -5 ligands. Poor IL-12 production correlated with a deficiency in intracellular reduced glutathione (GSH) concentrations in diabetic patients. Addition of GSH or N-acetylcysteine to PBMCs selectively restored IL-12 and IFN-γ production and improved bacterial killing. Furthermore, the depletion of GSH in mice led to increased susceptibility to melioidosis, reduced production of IL-12p70, and poorer disease outcome. Our data thus establish a link between GSH deficiency in diabetes and increased susceptibility to melioidosis that may open up new therapeutic avenues to protect diabetic patients against some intracellular bacterial pathogens.

Spinal muscular atrophy (SMA) is typically characterized as a motor neuron disease, but extraneuronal phenotypes are present in almost every organ in severely affected patients and animal models. Extraneuronal phenotypes were previously underappreciated, as patients with severe SMA phenotypes usually died in infancy; however, with current treatments for motor neurons increasing patient lifespan, impaired function of peripheral organs may develop into significant future comorbidities and lead to new treatment-modified phenotypes. Fatty liver is seen in SMA animal models, but generalizability to patients and whether this is due to hepatocyte-intrinsic survival motor neuron (SMN) protein deficiency and/or subsequent to skeletal muscle denervation is unknown. If liver pathology in SMA is SMN dependent and hepatocyte intrinsic, this suggests SMN-repleting therapies must target extraneuronal tissues and motor neurons for optimal patient outcome. Here, we showed that fatty liver is present in SMA patients and that SMA patient-specific induced pluripotent stem cell-derived hepatocyte-like cells were susceptible to steatosis. Using proteomics, functional studies, and CRISPR/Cas9 gene editing, we confirmed that fatty liver in SMA is a primary SMN-dependent hepatocyte-intrinsic liver defect associated with mitochondrial and other hepatic metabolism implications. These pathologies require monitoring and indicate the need for systematic clinical surveillance and additional and/or combinatorial therapies to ensure continued SMA patient health.

An accurate depiction of the convalescent COVID-19 immunome will help delineate the immunological milieu crucial for disease resolution and protection. Using mass cytometry, we characterized the immune architecture in patients recovering from mild COVID-19. We identified a virus-specific immune rheostat composed of an effector T (T eff ) cell recall response that is balanced by the enrichment of a highly specialized regulatory T (T reg ) cell subset. Both components were reactive against a peptide pool covering the receptor binding domain (RBD) of the SARS-CoV-2 spike glycoprotein. We also observed expansion of IFNγ + memory CD4 + T cells and virus-specific follicular helper T (T FH ) cells. Overall, these findings pinpoint critical immune effector and regulatory mechanisms essential for a potent, yet harmless resolution of COVID-19 infection.

Individuals with type 2 diabetes are at increased risk of acquiring melioidosis, a disease caused by Burkholderia pseudomallei infection. Although up to half of melioidosis patients have underlying diabetes, the mechanisms involved in this increased susceptibility are unknown. We found that B. pseudomallei-infected PBMCs from dia-betic patients were impaired in IL-12p70 production, which resulted in decreased IFN-γ induction and poor bac-terial killing. The defect was specific to the IL-12-IFN- γ axis. Defective IL-12 production was also observed during Mycobacterium tuberculosis infection, in which diabetes is likewise known to be a strong risk factor. In contrast, IL-12 production in diabetic cells was not affected upon Salmonella enterica infection or in response to TLR2, -3, -4, and -5 ligands. Poor IL-12 production correlated with a deficiency in intracellular reduced glutathione (GSH) concentrations in diabetic patients. Addition of GSH or N-acetylcysteine to PBMCs selectively restored IL-12 and IFN- γ production and improved bacterial killing. Furthermore, the depletion of GSH in mice led to increased susceptibility to melioidosis, reduced production of IL-12p70, and poorer disease outcome. Our data thus establish a link between GSH deficiency in diabetes and increased susceptibility to melioidosis that may open up new therapeutic avenues to protect diabetic patients against some intracellular bacterial pathogens.