Background Acute kidney injury (AKI) is a major post-surgical complication that contributes to morbidity and mortality. AKI is well documented after cardiac surgery. However, less is known regarding ...the incidence and risk factors following major non-cardiac surgery. Globally the incidence of AKI post major surgery has been evaluated; however, there are no data available for South Africa (SA).Objectives To ascertain the incidence of AKI after major non-cardiac surgery at a tertiary academic SA hospital. Secondary outcomes were to identify perioperative risk factors that are associated with an elevated risk to develop AKI in the postoperative period.Methods The study was conducted at Tygerberg Hospital, a single tertiary centre in Cape Town, SA. Perioperative records of adults who underwent major non-cardiac surgery were retrospectively collected. Variables pertaining to potential risk factors for AKI were captured, and serum creatinine levels were recorded up to 7 days postoperatively and compared with baseline measurements to determine whether AKI had developed. Descriptive statistics along with logistic regression analysis were used to interpret results.Results The overall incidence of AKI was 11.2% (95% confidence interval (CI) 9.8 - 12.6). Based on surgical discipline, trauma surgery (19%), followed by abdominal (18.5%) and vascular surgery (17%) had the highest incidence. Independent AKI risk factors were identified after multivariate analysis. These were: chronic obstructive pulmonary disease (odds ratio (OR) 2.19; 95% CI 1.09 - 4.37; p=0.005), trauma surgery (OR 3.00; 95% CI 1.59 - 5.64; p=0.001), abdominal surgery (OR 2.14; 95% CI 1.33 - 3.45; p=0.002), vascular surgery (OR 2.42; 95% CI 1.31 - 4.45; p=0.004), urology procedures (OR 2.45; 95% CI 1.31 - 4.45; p=0.005), red blood cell transfusion (OR 1.81; 95% CI 1.21 - 2.70; p=0.004), emergency surgery (OR 1.74; 95% CI 1.15 - 2.65; p=0.009) and inotrope use (OR 2.77; 95% CI 1.80 - 4.26; p
Environmental exposure to lead (Pb) is reported to associate with the development of Alzheimer's disease, where the formation of β‐amyloid peptides (APs) of (1‐40), (1‐42), and (25‐35) is considered ...as the major risk factor. In this context, we aimed at investigating the effect of epigallocatechin gallate (EGCG), a major flavonoid polyphenol available in green tea, in mitigating the individual and combined toxicity generated by Pb and β‐APs in terms of oxidative stress and apoptosis in human neuronal cells. SH‐SY5Y cells were exposed to Pb and β‐APs of (1‐40) and (25‐35) individually and in different combinations in the presence and absence of EGCG. The results indicated that EGCG mitigated both Pb‐ and β‐AP‐induced oxidative stress in scavenging reactive oxygen species and apoptosis by improving the expression levels of Bax and bcl2 and inhibiting annexin V and caspase‐3. Thus, our study shows that EGCG protects SH‐SY5Y cells against the cytotoxicity induced by Pb and β‐APs by decreasing oxidative stress and inhibiting apoptosis.
Infection or inflammation may precede and trigger formation of microvascular thrombosis in patients with acquired thrombotic thrombocytopenic purpura (TTP). However, the mechanism underlying this ...clinical observation is not fully understood. Here, we show that human neutrophil peptides (HNPs) released from activated and degranulated neutrophils inhibit proteolytic cleavage of von Willebrand factor (VWF) by ADAMTS13 in a concentration-dependent manner. Half-maximal inhibitory concentrations of native HNPs toward ADAMTS13-mediated proteolysis of peptidyl VWF73 and multimeric VWF are 3.5 μM and 45 μM, respectively. Inhibitory activity of HNPs depends on the RRY motif that is shared by the spacer domain of ADAMTS13. Native HNPs bind to VWF73 (KD = 0.72 μM), soluble VWF (KD = 0.58 μM), and ultra-large VWF on endothelial cells. Enzyme-linked immunosorbent assay (ELISA) demonstrates markedly increased plasma HNPs1-3 in most patients with acquired autoimmune TTP at presentation (median, ∼170 ng/mL; range, 58-3570; n = 19) compared with healthy controls (median, ∼23 ng/mL; range, 6-44; n = 18) (P < .0001). Liquid chromatography plus tandem mass spectrometry (LC-MS/MS) reveals statistically significant increases of HNP1, HNP2, and HNP3 in patient samples (all P values <.001). There is a good correlation between measurement of HNPs1-3 by ELISA and by LC-MS/MS (Spearman ρ = 0.7932, P < .0001). Together, these results demonstrate that HNPs1-3 may be potent inhibitors of ADAMTS13 activity, likely by binding to the central A2 domain of VWF and physically blocking ADAMTS13 binding. Our findings may provide a novel link between inflammation/infection and the onset of microvascular thrombosis in acquired TTP and potentially other immune thrombotic disorders.
•HNPs inhibit proteolytic cleavage of VWF by ADAMTS13 by physically blocking VWF-ADAMTS13 interactions.•Plasma levels of HNP1, HNP2, and HNP3 are markedly increased in patients with acquired autoimmune TTP.
Stress can exert long-lasting changes on the brain that contribute to vulnerability to mental illness, yet mechanisms underlying this long-term vulnerability are not well understood. We hypothesized ...that stress may alter the production of oligodendrocytes in the adult brain, providing a cellular and structural basis for stress-related disorders. We found that immobilization stress decreased neurogenesis and increased oligodendrogenesis in the dentate gyrus (DG) of the adult rat hippocampus and that injections of the rat glucocorticoid stress hormone corticosterone (cort) were sufficient to replicate this effect. The DG contains a unique population of multipotent neural stem cells (NSCs) that give rise to adult newborn neurons, but oligodendrogenic potential has not been demonstrated in vivo. We used a nestin-CreER/YFP transgenic mouse line for lineage tracing and found that cort induces oligodendrogenesis from nestin-expressing NSCs in vivo. Using hippocampal NSCs cultured in vitro, we further showed that exposure to cort induced a pro-oligodendrogenic transcriptional program and resulted in an increase in oligodendrogenesis and decrease in neurogenesis, which was prevented by genetic blockade of glucocorticoid receptor (GR). Together, these results suggest a novel model in which stress may alter hippocampal function by promoting oligodendrogenesis, thereby altering the cellular composition and white matter structure.
Near-infrared (NIR) luminescent CuInS2-ZnS alloyed nanocrystals (CIZS-NCs) for highly fluorescence bioimaging have received considerable interest in recent years. Owing, they became a desirable ...alternative to heavy-metal based-NCs and organic dyes with unique optical properties and low-toxicity for bioimaging and optoelectronic applications. In the present study, bright and robust CIZS-NCs have been synthesized within 5 min, as-high-as 230 °C without requiring any inert-gas atmosphere via microwave-solvothermal (MW-ST) method. Subsequently, the in vitro and in vivo nano-xenotoxicity and cellular uptake of the MUA-functionalized CIZS-NCs were investigated in L929, Vero, MCF7 cell lines and zebrafish-embryos. We observed minimal toxicity and acute teratogenic consequences upto 62.5 μg/ml of the CIZS-NCs in zebrafish-embryos. We also observed spontaneous uptake of the MUA-functionalized CIZS-NCs by 3 dpf older zebrafish-embryos that are evident through bright red fluorescence-emission at a low concentration of 7.8 μg/mL. Hence, we propose that the rapid, low-cost, large-scale "sustainable" MW-ST synthesis of CIZS-NCs, is an ideal bio-nanoprobe with good temporal and spatial resolution for rapid labeling, long-term in vivo tracking and intravital-fluorescence-bioimaging (IVBI).
Low- and middle-income countries have a critical shortage of specialist anaesthetists. Most patients arriving for surgery are of low perioperative risk. Without immediate access to preoperative ...specialist care, an appropriate interim strategy may be to ensure that only high-risk patients are seen preoperatively by a specialist. Matching human resources to the burden of disease with a nurse-administered pre-operative screening tool to identify high-risk patients who might benefit from specialist review prior to the day of surgery may be an effective strategy.
To develop a nurse-administered preoperative anaesthesia screening tool to identify patients who would most likely benefit from a specialist review before the day of surgery, and those patients who could safely be seen by the anaesthetist on the day of surgery. This would ensure adequate time for optimisation of high-risk patients preoperatively and limit avoidable day-of-surgery cancellations.
A systematic review was conducted to identify preoperative screening questions for use in a three-round Delphi consensus process. A panel of 16 experienced full-time clinical anaesthetists representing all university-affiliated anaesthesia departments in South Africa participated to define a nurses' screening tool for preoperative assessment.
Ninety-eight studies were identified, which generated 79 questions. An additional 14 items identified by the facilitators were added to create a list of 93 questions for the first round. The final screening tool consisted of 81 questions, of which 37 were deemed critical to identify patients who should be seen by a specialist prior to the day of surgery.
A structured nurse-administered preoperative screening tool is proposed to identify high-risk patients who are likely to benefit from a timely preoperative specialist anaesthetist review to avoid cancellation on the day of surgery.
Chronic pain occurs when pain transitions from an acute to a chronic state, especially when acute pain is not effectively managed. In the presence of continuous acute pain, pain processing and ...pathways gradually undergo several structural and functional modifications in a process known as sensitisation. These modifications may occur in the peripheral or central nervous system. The consequences of these modifications include decreased pain threshold, increased excitability and increased responsiveness to pain. A combination of all of these changes result in the conversion of acute to chronic pain. This review summarises the pathophysiological alterations that are involved in pain chronification. However, these changes and mechanisms are not as simplistic as presented here, as the mechanisms involved are far more complex. The presentation adopted is for the benefit of a basic understanding and not a comprehensive treatise on chronic pain mechanisms.
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