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Abstract Background Deep sternal wound infection (DSWI) constitutes a serious complication after coronary artery bypass grafting (CABG) surgery. The aim of this study is to evaluate the dose-response relationship between glycated hemoglobin (HbA1c) level and the risk of DSWI after CABG. Methods PubMed, Scopus, and Cochrane Library databases were searched to identify potentially relevant articles. According to rigorous inclusion and exclusion criteria, fourteen studies including 15,570 patients were enrolled in our meta-analysis. Odds ratio (OR) with 95% confidence intervals (CIs) was used as the summary statistic. The robust-error meta-regression model was used to synthesize the dose-response relationship. Results Our meta-analysis shows that among patients undergoing CABG, preoperative elevated HbA1c was associated with the risk of developing DSWI (OR = 2.67, 95% CI 2.00–3.58) but with low prognostic accuracy (diagnostic OR = 2.70, 95% CI 1.96–3.73; area under the curve = 0.66, 95% CI 0.62–0.70) for predicting postoperative DSWI. Subgroup analyses showed the relationship became nonsignificant in patients without diabetes and studies adopting lower HbA1c thresholds. Dose-response analysis showed a significant nonlinear (p = 0.03) relationship between HbA1c and DSWI, with a significantly increased risk of DSWI when HbA1c was > 5.7%. Conclusions An elevated HbA1c level of > 5.7% was related to a higher risk of developing DSWI after CABG, and the risk increased as the HbA1c level grew. The association between HbA1c and DSWI was nonsignificant among nondiabetic patients while significant among diabetic patients.

Abstract It is important for the clinician to be familiar with interpreting a variety of radiological modalities that provide vital information that will aid in the preoperative planning, counseling, and subsequent management of patients with retrosternal goiter.

Tephrosia apollinea is a perennial shrublet widely distributed in Africa and is known to have medicinal properties. The current study describes the bio-assay (cytotoxicity) guided isolation of (-)-pseudosemiglabrin from the aerial parts of T. apollinea. The structural and stereochemical features have been described using spectral and x-ray crystallographic techniques. The cytotoxicity of isolated compound was evaluated against nine cancer cell lines. In addition, human fibroblast was used as a model cell line for normal cells. The results showed that (-)-pseudosemiglabrin exhibited dose-dependent antiproliferative effect on most of the tested cancer cell lines. Selectively, the compound showed significant inhibitory effect on the proliferation of leukemia, prostate and breast cancer cell lines. Further studies revealed that, the compound exhibited proapoptotic phenomenon of cytotoxicity. Interestingly, the compound did not display toxicity against the normal human fibroblast. It can be concluded that (-)-pseudosemiglabrin is worthy for further investigation as a potential chemotherapeutic agent.

Flow separation and reattachment of 0.2% TiO2 nanofluid in an asymmetric abrupt expansion is studied in this paper. Such flows occur in various engineering and heat transfer applications. Computational fluid dynamics package (FLUENT) is used to investigate turbulent nanofluid flow in the horizontal double-tube heat exchanger. The meshing of this model consists of 43383 nodes and 74891 elements. Only a quarter of the annular pipe is developed and simulated as it has symmetrical geometry. Standard k-epsilon second order implicit, pressure based-solver equation is applied. Reynolds numbers between 17050 and 44545, step height ratio of 1 and 1.82 and constant heat flux of 49050 W/m2 was utilized in the simulation. Water was used as a working fluid to benchmark the study of the heat transfer enhancement in this case. Numerical simulation results show that the increase in the Reynolds number increases the heat transfer coefficient and Nusselt number of the flowing fluid. Moreover, the surface temperature will drop to its lowest value after the expansion and then gradually increase along the pipe. Finally, the chaotic movement and higher thermal conductivity of the TiO2 nanoparticles have contributed to the overall heat transfer enhancement of the nanofluid compare to the water.

Microglia, the brain's resident macrophages, can be reconstituted by surrogate cells - a process termed "microglia replacement." To expand the microglia replacement toolkit, we here introduce estrogen-regulated (ER) homeobox B8 (Hoxb8) conditionally immortalized macrophages, a cell model for generation of immune cells from murine bone marrow, as a versatile model for microglia replacement. We find that ER-Hoxb8 macrophages are highly comparable to primary bone marrow-derived (BMD) macrophages in vitro, and, when transplanted into a microglia-free brain, engraft the parenchyma and differentiate into microglia-like cells. Furthermore, ER-Hoxb8 progenitors are readily transducible by virus and easily stored as stable, genetically manipulated cell lines. As a demonstration of this system's power for studying the effects of disease mutations on microglia in vivo, we created stable, Adar1 -mutated ER-Hoxb8 lines using CRISPR-Cas9 to study the intrinsic contribution of macrophages to Aicardi-Goutières Syndrome (AGS), an inherited interferonopathy that primarily affects the brain and immune system. We find that Adar1 knockout elicited interferon secretion and impaired macrophage production in vitro, while preventing brain macrophage engraftment in vivo - phenotypes that can be rescued with concurrent mutation of Ifih1 (MDA5) in vitro, but not in vivo. Lastly, we extended these findings by generating ER-Hoxb8 progenitors from mice harboring a patient-specific Adar1 mutation (D1113H). We demonstrated the ability of microglia-specific D1113H mutation to drive interferon production in vivo, suggesting microglia drive AGS neuropathology. In sum, we introduce the ER-Hoxb8 approach to model microglia replacement and use it to clarify macrophage contributions to AGS.

The Par complex dynamically polarizes to the apical cortex of asymmetrically dividing Drosophila neuroblasts where it directs fate determinant segregation. Previously, we showed that apically directed cortical movements that polarize the Par complex require F-actin (Oon and Prehoda, 2019). Here, we report the discovery of cortical actomyosin dynamics that begin in interphase when the Par complex is cytoplasmic but ultimately become tightly coupled to cortical Par dynamics. Interphase cortical actomyosin dynamics are unoriented and pulsatile but rapidly become sustained and apically-directed in early mitosis when the Par protein aPKC accumulates on the cortex. Apical actomyosin flows drive the coalescence of aPKC into an apical cap that depolarizes in anaphase when the flow reverses direction. Together with the previously characterized role of anaphase flows in specifying daughter cell size asymmetry, our results indicate that multiple phases of cortical actomyosin dynamics regulate asymmetric cell division., Competing Interests: CO, KP No competing interests declared, (© 2021, Oon and Prehoda.)

Wnt signalling drives many processes in development, homeostasis and disease; however, the role and mechanism of individual ligand-receptor (Wnt-Frizzled (Fzd)) interactions in specific biological processes remain poorly understood. Wnt9a is specifically required for the amplification of blood progenitor cells during development. Using genetic studies in zebrafish and human embryonic stem cells, paired with in vitro cell biology and biochemistry, we determined that Wnt9a signals specifically through Fzd9b to elicit β-catenin-dependent Wnt signalling that regulates haematopoietic stem and progenitor cell emergence. We demonstrate that the epidermal growth factor receptor (EGFR) is required as a cofactor for Wnt9a-Fzd9b signalling. EGFR-mediated phosphorylation of one tyrosine residue on the Fzd9b intracellular tail in response to Wnt9a promotes internalization of the Wnt9a-Fzd9b-LRP signalosome and subsequent signal transduction. These findings provide mechanistic insights for specific Wnt-Fzd signals, which will be crucial for specific therapeutic targeting and regenerative medicine.

During the asymmetric divisions of Drosophila neuroblasts, the Par polarity complex cycles between the cytoplasm and an apical cortical domain that restricts differentiation factors to the basal cortex. We used rapid imaging of the full cell volume to uncover the dynamic steps that underlie transitions between neuroblast polarity states. Initially, the Par proteins aPKC and Bazooka form discrete foci at the apical cortex. Foci grow into patches that together comprise a discontinuous, unorganized structure. Coordinated cortical flows that begin near metaphase and are dependent on the actin cytoskeleton rapidly transform the patches into a highly organized apical cap. At anaphase onset, the cap disassembles as the cortical flow reverses direction toward the emerging cleavage furrow. Following division, cortical patches dissipate into the cytoplasm allowing the neuroblast polarity cycle to begin again. Our work demonstrates how neuroblasts use asymmetric recruitment and cortical flows to dynamically polarize during asymmetric division cycles., Competing Interests: CO, KP No competing interests declared, (© 2019, Oon and Prehoda.)

Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 has been applied to edit genomes in a wide variety of model systems. Although this process can be quite efficient, editing at precise locations in the genome remains difficult without a suitable single guide RNA (sgRNA). We have developed a method for screening sgRNA function in vitro, using reagents that most zebrafish laboratories are already using. The results from our in vitro assay correlate with function in vivo in every sgRNA that we have examined so far. When combined with endonucleases with alternative protospacer adjacent motif site specificities and alternative sgRNAs, this method will streamline genome editing at almost any locus.

We propose a new simple, low-cost method for providing all-round metal contacts to one-dimensional structures such as carbon nanotubes and nanowires on a transparent substrate. The nanostructures are first positioned in place to bridge a electrode gap by dielectrophoresis. The electrode structure is then used as a self-aligned mask during the subsequent photolithography through illumination from the substrate backside. This is followed by metallization and lift-off. Our measurements on multi-walled carbon nanotubes thus contacted show reasonable yield and good electrical contacts for the process carried out on a glass slide as the substrate.

This study reviews the records of all cardiac life support training courses conducted at the Ministry of Health's Life Support Training Centre situated in Singapore General Hospital over a six period from 1985 to 1990. A total of 1,789 persons were trained in Basic Life Support (BCLS), 65 as BCLS Instructors, 267 in Advanced Cardiac Life Support (ACLS), 276 in Emergency Cardiac Care (ECC) and 24 in Emergency Cardiac Defibrillation (ECD). These courses have involved a total of 1111 doctors, 1248 nurses and 62 ancillary staff. At the end of the course, 90.7% of those learning BCLS agreed that they would use their CPR skills, if required. Only 60% felt they would use mouth-to-mouth ventilation. Of 415 who expressed an interest in becoming instructors, 15.7% have, to-date, been trained. While more than 80% of persons learning, ACLS were doctors, only 25% of these were willing to instruct. There are currently 14 ACLS instructors. The ECC courses were modified from the ACLS course and taught to Emergency Room doctors only. It was found to be immensely popular with 98% expressing benefit. The ECD programme trained emergency ambulance nurses in the use of semi-automatic electrical defibrillators. The marked increased in yearning for cardiac life support skills amongst medical and nursing staff has been a major factor in the proliferation of life support training programmes at the Centre. Nurturing this enthusiasm is the key to ensuring that the programmes continue to expand for the benefit of both inpatients and the out-of-hospital lay public.

Adverse Drug Reaction reporting was made mandatory in the Singapore General Hospital in January 1978. Reports on a total of 59 patients were received on 34 drugs ranging from antibiotics to Chinese medicine. Antimicrobial drugs topped the list of adverse reactions. The most frequently reported drugs in decreasing order of reports were ampicillin, allopurinol, aspirin compound preparations, cloxacillin, digoxin, streptomycin, penicillins and insulins. Allergies were the most common reactions seen.

The deleterious effects of raised plasma lipids on the progression of coronary artery disease has been well established. Recent research data suggests that intensive lipid lowering represents a new approach to Cardiac Rehabilitation. There was a total of twenty-four participants with twenty-one (87.5%) males and three (12.5%) females. There were seventeen Chinese (70.8%), six Indians (25%) and one Malay (4.2%). Their ages ranged from group forty to forty-nine, five participants (20%); fifty to fifty-nine, twelve participants (50%); sixty to sixty-nine, six participants (25%) and seventy to seventy-nine, one participant (5%). In this study, twelve individuals were treated with Cholestyramine, seven by Gemfibrozil, four by Clofibrate and three by Bezafibrate. The duration of antilipid treatment ranged from two to eighteen months (mean eight months). Side effects were reported in twelve patients (50%) on Cholestyramine who complained of constipation while one (4%) on Bezafibrate had abnormal liver function tests (raised SGOT and SGPT). All patients had been on an exercise and diet control program for one year which they were enrolled in an intensive lipid-lowering protocol. The pre and post treatment lipid profiles with lipid-lowering agents showed 18% reduction for Triglycerides, 15% reduction for Total Cholesterol, 5% increase for HDL-Cholesterol, 19% decrease in LDL Cholesterol, 19% decrease in Total Cholesterol: HDL ratios. The initial results suggest that an intensive lipid-lowering strategy in a Cardiac Rehabilitation Program appears to have a beneficial effect on lipid profiles and represents an expanded approach to lipid management involving exercise, nutrition and pharmacological intervention.

The concept of stress management was reviewed in this paper. Stress was conceptualised as a perception of inability to cope with its attendant emotional and psychophysiological responses. Management of stress then has to do with altering environmental triggers where possible. Alteration to more realistic mode of perception, adoption of more adaptive means of emotional response as well as the modulation of the body's psychophysiological state through the use of various relaxation techniques would all help to reduce stress and enable the individual to cope with it. The role of biofeedback in promoting the relaxation response as well as training the individual to adapt to better means of coping was discussed. Thirty-three anxious patients who were treated with biofeedback assisted relaxation training were studied for their response on EMG reading and heart rate. Their psychosocial functioning on an experiential index also showed an improvement. It was concluded that whatever techniques are used, a multi-modal approach to stress management is probably the more effective in helping people to cope with the variety of stress faced in life.

The Singapore General Hospital Cardiac Rehabilitation and Health Enhancement Programme has taken in 148 patients since its inception in 1979. The programme initially admitted post myocardial infarction patients but has expanded to include those with coronary by pass surgery. In 1982 the programme developed a health enhancement and preventive cardiology role by taking in participants at high risk--hypertension, obesity, diabetes mellitus and hyperlipidemia. There has been no exercise prescription related deaths during the exercises.

Effective use of Cardiopulmonary Resuscitation (CPR) saves lives both in and out of hospitals. Yet, in Singapore, this practical skill is rarely taught even within the medical community. Observations from a CPR pilot training programme at the Singapore General Hospital expose this glaring deficiency in our health system. Urgent remedial measures are needed.