A pedagogical approach for the development and optimization of a novel mix of biowastes-derived hydroxyapatite using the Box-Behnken experimental design.

The current study details the creation of synthetic hydroxyapatite (HAp) using a combination of catfish and bovine bones (C&B). This is done to design the optimum processing parameters and consolidate instructional strategies to develop HAp scaffolds for biomedical engineering. The HAp produced from the novel mix of the biogenic materials (C&B) was through calcination and supported with the sol-gel technique, sintering, and low-cold compaction pressure. The ideal preparation conditions were identified with the aid of the Box-Behnken statistical design in response surface methodology. To understand the physicochemical and mechanical properties of the formulation, analytical studies on the synthesized HAp were carried out. To establish a substantial relation between the physicomechanical properties of the produced HAp scaffolds, three parameters- sintering temperature, compaction loads, and holding times were used. In the evaluation, the sintering temperature was found to have the greatest impact on the material's physicomechanical properties, with compressive strength (13 MPa), porosity (49.45 %), and elastic modulus (2.216 GPa) being the most enhanced properties in that order. The physicomechanical characteristics of the HAp scaffolds were at their optimal at 900 °C, 1 h 18 min of holding time, and 311.73 Pa of compaction pressure. X-ray diffraction (XRD) and Fourier transform infrared (FTIR) results showed that powders with a dominant HAp phase were produced at all runs, including the optimum run. Therefore, using a computationally effective methodology that is helpful for novelties in biomedical engineering education, this study demonstrates the optimal process for the synthesis of a novel matrix bone-derived HAp, showing the most significant relations liable for manufacturing medically suitable HAp scaffolds from the mixture of bovine and catfish bones.

Discrepancies between clinical diagnoses and autopsy findings: A comparative study conducted in South Africa.

BACKGROUND: The anatomical pathology autopsy serves several purposes, notably as a quality management tool for evaluation of accuracy in clinical diagnosis. Despite its value, for various reasons there has been an international decline in autopsies conducted. In the modern medical era, with all its advances in technology, diagnostic techniques and interventions, there is still a high discrepancy between clinical diagnoses and postmortem findings. OBJECTIVES: To establish the discrepancies between clinical diagnoses and postmortem findings in anatomical pathology autopsies. METHODS: A retrospective, descriptive study was conducted over the 4-year-period 2014 - 2017. The clinical diagnoses and postmortem findings of cases referred to the Department of Anatomical Pathology at the University of Pretoria, South Africa, were evaluated and compared using the modified Goldman criteria. RESULTS: A total of 288 cases qualified for the study and were evaluated. The gender distribution was 155 (53.8%) male and 133 (48.2%) female, with the majority of cases in the age group 19 - 60 years (mean 36.4). The majority of the cases were referred by internal medicine, followed by paediatrics. The most common cause of death in major missed diagnoses was pulmonary conditions. Of the cases, 115 (39.3%) had a major discrepancy and 62 (21.5%) a minor discrepancy. CONCLUSION: This study showed that there is still a high discrepancy between clinical diagnoses and postmortem findings, similar to studies conducted globally. The current COVID-19 pandemic may be a driver for revival of the anatomical pathology autopsy, and future studies are recommended to evaluate whether the decline can be reversed.

Discrepancies between clinical diagnoses and autopsy findings: A comparative study conducted in South Africa

The anatomical pathology autopsy serves several purposes, notably as a quality management tool for evaluation of accuracy in clinical diagnosis. Despite its value, for various reasons there has been an international decline in autopsies conducted. In the modern medical era, with all its advances in technology, diagnostic techniques and interventions, there is still a high discrepancy between clinical diagnoses and postmortem findings.Objectives. To establish the discrepancies between clinical diagnoses and postmortem findings in anatomical pathology autopsies.Methods. A retrospective, descriptive study was conducted over the 4-year-period 2014 - 2017. The clinical diagnoses and postmortem findings of cases referred to the Department of Anatomical Pathology at the University of Pretoria, South Africa, were evaluated and compared using the modified Goldman criteria.Results. A total of 288 cases qualified for the study and were evaluated. The gender distribution was 155 (53.8%) male and 133 (48.2%) female, with the majority of cases in the age group 19 - 60 years (mean 36.4). The majority of the cases were referred by internal medicine, followed by paediatrics. The most common cause of death in major missed diagnoses was pulmonary conditions. Of the cases, 115 (39.3%) had a major discrepancy and 62 (21.5%) a minor discrepancy.Conclusion. This study showed that there is still a high discrepancy between clinical diagnoses and postmortem findings, similar to studies conducted globally. The current COVID-19 pandemic may be a driver for revival of the anatomical pathology autopsy, and future studies are recommended to evaluate whether the decline can be reversed

Optimization of extrusion process parameter in manufacture of ilmenite TiO2 reinforced pencil lead.

The production of pencil lead with the inclusion of ilmenite for strength improvement and product wear control especially during production was investigated. A Response Surface Methodology (RSM) based on three numeric factors and two center points thus generating sixteen runs was used as tool for the optimization of production process parameters. The major raw materials which are graphite clay and ilmenite were characterized using X-ray fluorescence technique while the surface morphology was studied using scanning Electronic microscopy. The studied input variables were ram pressure, moisture content and die dead angle. Also, an experimental investigation of fracture force and wear rate of pencil lead were carried out. To obtain the optimum values of the properties being investigated, a tribometer and Micro Universal Testing Machine (MUTEM 4) were used for measurements, and response table was generated. The response surface plots showed that all three input variable had considerable impact on the responses. Results showed that the graphite used is made up majorly of carbon and ilmenite (TiO2). The control factor levels were applied to optimize the desired mechanical properties of reengineered pencil lead using the RSM. Results also showed that with a die angle of 55.3850oram pressure of 5.716Mpa and moisture content of 22.735, the optimal fracture force is 2.6055N, and optimal wear rate is 0.445 mm/l. These results were validated with those of industrially manufactured ones whose values are 2.95N and 0.35 mm/l respectively. It was concluded that ilmenite can serve as a good additive to pencil lead production.

Development of natural fibres reinforced composites for the production of orthopaedic cast.

This study gave an insight on how we can utilise the unique features of bio-composites of albumen-glycerol, reinforced with natural fibres in the production of orthopaedic cast. Studies on the use of natural fibres as a replacement to man-made fibres in fibre-reinforced composites has increased and opened up for further industrial possibilities. They have the advantages of low density, low cost, biodegradable and environmental friendly. However, the main disadvantages of natural fibres in manufacturing composites are the poor compatibility between fibre and matrix and the relatively high moisture sorption. Therefore, chemical treatments were used in modifying the fibres surface properties. This work documents an attempt to create an alternative fibre reinforced composite material for possible use in the replacement of Plaster of Paris (POP), used for making orthopaedic cast. The matrix is an albumen/glycerol mix and the fibres are raffia, kenaf and sisal fibres. The bio-composites were analysed by standard methods such as mechanical tests, TGA and SEM. The mechanical properties of this composite material showed a promising future in the orthopaedic field. Natural fibre cast as external immobilising is considered a better orthopaedic modality than the POP as it provides rigid fixation, less time consuming and fewer complications.

Publisher Correction: Suppression of insulin feedback enhances the efficacy of PI3K inhibitors.

In this Letter, author Xing Du was incorrectly listed as Du Xing; this has been corrected online.

Suppression of insulin feedback enhances the efficacy of PI3K inhibitors.

Mutations in PIK3CA, which encodes the p110α subunit of the insulin-activated phosphatidylinositol-3 kinase (PI3K), and loss of function mutations in PTEN, which encodes a phosphatase that degrades the phosphoinositide lipids generated by PI3K, are among the most frequent events in human cancers1,2. However, pharmacological inhibition of PI3K has resulted in variable clinical responses, raising the possibility of an inherent mechanism of resistance to treatment. As p110α mediates virtually all cellular responses to insulin, targeted inhibition of this enzyme disrupts glucose metabolism in multiple tissues. For example, blocking insulin signalling promotes glycogen breakdown in the liver and prevents glucose uptake in the skeletal muscle and adipose tissue, resulting in transient hyperglycaemia within a few hours of PI3K inhibition. The effect is usually transient because compensatory insulin release from the pancreas (insulin feedback) restores normal glucose homeostasis3. However, the hyperglycaemia may be exacerbated or prolonged in patients with any degree of insulin resistance and, in these cases, necessitates discontinuation of therapy3-6. We hypothesized that insulin feedback induced by PI3K inhibitors may reactivate the PI3K-mTOR signalling axis in tumours, thereby compromising treatment effectiveness7,8. Here we show, in several model tumours in mice, that systemic glucose-insulin feedback caused by targeted inhibition of this pathway is sufficient to activate PI3K signalling, even in the presence of PI3K inhibitors. This insulin feedback can be prevented using dietary or pharmaceutical approaches, which greatly enhance the efficacy/toxicity ratios of PI3K inhibitors. These findings have direct clinical implications for the multiple p110α inhibitors that are in clinical trials and provide a way to increase treatment efficacy for patients with many types of tumour.

Individual thrombin generation and spontaneous bleeding rate during personalized prophylaxis with Nuwiq® (human-cl rhFVIII) in previously treated patients with severe haemophilia A.

INTRODUCTION: For individuals with haemophilia A, prophylaxis with factor VIII (FVIII) is typically directed towards trough activity >1 IU/dL; however, some patients still experience spontaneous bleeding events (sBEs). AIM: Aims were to evaluate relationships of endogenous thrombin potential (ETP) and FVIII:C with occurrence of clinical bleeding. METHODS: GENA-21 was a prospective, open-label, phase IIIb study investigating the safety and efficacy of Nuwiq® (human-cl rhFVIII) in previously treated adults with severe haemophilia A. The study included a 72-hour pharmacokinetic (PK) evaluation phase and a 6-month personalized prophylaxis phase in which treatment was guided by PK parameters. This subanalysis assessed FVIII:C by one-stage assay and ETP by thrombin generation assay in blood samples. RESULTS: Baseline mean ETP was lower in the 7 patients who experienced sBEs during personalized prophylaxis versus 25 who did not (n = 32 with data from PK phase and prophylaxis phase; P = .0002). During personalized prophylaxis (n = 49), only patients with lower median trough ETP experienced sBEs (8/49 patients; ROC AUC = 0.9421; P < .0001); there was no significant relationship for FVIII:C in predicting sBEs (ROC AUC = 0.5838; P = .4750). Directly following infusion of human-cl rhFVIII, ETP was lower in patients who experienced sBEs versus those who did not (P = .0002), whereas FVIII:C did not differ significantly between these groups. CONCLUSIONS: In adults with severe haemophilia A and reduced thrombin generation, increased frequency of spontaneous bleeding was observed irrespective of trough FVIII levels. Thus, personalized prophylaxis should take into account variables other than FVIII:C. Large prospective trials are needed to verify ETP as a marker for spontaneous bleeding.

Design approach of an aquaculture cage system for deployment in the constructed channel flow environments of a power plant.

This study provides an engineering approach for designing an aquaculture cage system for use in constructed channel flow environments. As sustainable aquaculture has grown globally, many novel techniques have been introduced such as those implemented in the global Atlantic salmon industry. The advent of several highly sophisticated analysis software systems enables the development of such novel engineering techniques. These software systems commonly include three-dimensional (3D) drafting, computational fluid dynamics, and finite element analysis. In this study, a combination of these analysis tools is applied to evaluate a conceptual aquaculture system for potential deployment in a power plant effluent channel. The channel is supposedly clean; however, it includes elevated water temperatures and strong currents. The first portion of the analysis includes the design of a fish cage system with specific net solidities using 3D drafting techniques. Computational fluid dynamics is then applied to evaluate the flow reduction through the system from the previously generated solid models. Implementing the same solid models, a finite element analysis is performed on the critical components to assess the material stresses produced by the drag force loads that are calculated from the fluid velocities.

Optimising perioperative care for hip and knee arthroplasty in South Africa: a Delphi consensus study.

BACKGROUND: A structured approach to perioperative patient management based on an enhanced recovery pathway protocol facilitates early recovery and reduces morbidity in high income countries. However, in low- and middle-income countries (LMICs), the feasibility of implementing enhanced recovery pathways and its influence on patient outcomes is scarcely investigated. To inform similar practice in LMICs for total hip and knee arthroplasty, it is necessary to identify potential factors for inclusion in such a programme, appropriate for LMICs. METHODS: Applying a Delphi method, 33 stakeholders (13 arthroplasty surgeons, 12 anaesthetists and 8 physiotherapists) from 10 state hospitals representing 4 South African provinces identified and prioritised i) risk factors associated with poor outcomes, ii) perioperative interventions to improve outcomes and iii) patient and clinical outcomes necessary to benchmark practice for patients scheduled for primary elective unilateral total hip and knee arthroplasty. RESULTS: Thirty of the thirty-three stakeholders completed the 3 months Delphi study. The first round yielded i) 36 suggestions to preoperative risk factors, ii) 14 (preoperative), 18 (intraoperative) and 23 (postoperative) suggestions to best practices for perioperative interventions to improve outcomes and iii) 25 suggestions to important postsurgical outcomes. These items were prioritised by the group in the consecutive rounds and consensus was reached for the top ten priorities for each category. CONCLUSION: The consensus derived risk factors, perioperative interventions and important outcomes will inform the development of a structured, perioperative multidisciplinary enhanced patient care protocol for total hip and knee arthroplasty. It is anticipated that this study will provide the construct necessary for developing pragmatic enhanced care pathways aimed at improving patient outcomes after arthroplasty in LMICs.

Comparison of citrated and fresh whole blood for viscoelastic coagulation testing during elective neurosurgery.

BACKGROUND: Previous viscoelastic haemostatic tests studies have often indicated a hypercoagulative test signal with citrated blood, which could influence clinical decision makings. PURPOSE: The aim of this study was to compare fresh and citrated whole blood using two non-automated viscoelastic ROTEM and Sonoclot tests. Our hypothesis was that citrated blood would demonstrate a hypercoagulative response in this setting, not tested before. METHODS: Perioperative viscoelastic coagulation changes were evaluated with a ROTEM and Sonoclot in 38 patients undergoing elective brain tumor surgery. The citrated samples were recalcified with CaCl2. Wilcoxon nonparametric-paired tests and Bland-Altman plots were performed to compare the fresh and citrated blood analyses. RESULTS: The citrated blood showed a hypercoagulative response in ROTEM NATEM-clot formation time and α-angle, Sonoclot-clot rate and platelet function, as compared to fresh blood (p<0.0001). CONCLUSIONS: Fresh whole blood may theoretically reflect in vivo haemostasis more closely than citrated analyses, which indicated a hypercoagulative response as compared to the fresh whole blood analyses Bland-Altman plots also indicated that ROTEM reference ranges in patients undergoing brain surgery should be redefined. Future studies must establish the correlation between viscoelastic test results using fresh or citrate anticoagulated blood and clinical outcomes, such as bleeding, transfusion or reoperation for postoperative haematoma.

Spatial and temporal analogies in microbial communities in natural drinking water biofilms.

Biofilms are ubiquitous throughout drinking water distribution systems (DWDS), playing central roles in system performance and delivery of safe clean drinking water. However, little is known about how the interaction of abiotic and biotic factors influence the microbial communities of these biofilms in real systems. Results are presented here from a one-year study using in situ sampling devices installed in two operational systems supplied with different source waters. Independently of the characteristics of the incoming water and marked differences in hydraulic conditions between sites and over time, a core bacterial community was observed in all samples suggesting that internal factors (autogenic) are central in shaping biofilm formation and composition. From this it is apparent that future research and management strategies need to consider the specific microorganisms found to be able to colonise pipe surfaces and form biofilms, such that it might be possible to exclude these and hence protect the supply of safe clean drinking water.

Outcomes between older adults with atypical and typical femoral fractures are comparable.

INTRODUCTION: Atypical femoral fractures (AFFs) are rare but a serious complication associated with prolonged use of bisphosphonates. However little is known about clinical outcomes of AFFs. The aim of this study is to compare the characteristics and postoperative outcomes between older patients with AFFs and typical femoral fractures (TFFs). METHODS: A retrospective matched cohort study (each AFF was age- and sex-matched with three TFFs) of patients aged 65 years or older who were admitted to The Queen Elizabeth Hospital, South Australia between January 2011 and December 2013 was undertaken. Baseline characteristics of both groups were compared. The primary outcomes evaluated were level of independence in mobility at discharge and 3 months after surgery. Secondary outcomes included length of hospital stay, post-operative complications, rate of surgical revision, discharge destination (after acute hospital stay or rehabilitation), 28-day hospital readmission and 12-month mortality. RESULTS: Ten patients (mean age: 78.1 years) with AFFs were compared with 30 matched TFFs. Patients with AFFs were predominantly female (90%) and 80% had been taking oral bisphosphonate. Nine of the AFFs had their fractures fixed with an intramedullary (IM) nail. The level of independent mobility at discharge (OR 0.31; 95%CI: 0.06-1.71; p=0.26) and at 3 months (OR 0.51; 95%CI: 0.10-2.53; p=0.47) were comparable between the two groups. Only one AFF patient treated with plate and screws required surgical revision, compared with none in the TFF group. Secondary outcomes were not significantly different between the two groups. CONCLUSION: Recovery of mobility and reoperation rates after surgery of patients with AFFs were favourable and did not differ significantly from TFFs. Further consideration should be given to using IM fixation in the management of AFFs in older people.

Adrenocorticotropic hormone analog use for podocytopathies.

BACKGROUND: Adrenocorticotropic hormone is being increasingly studied for treatment of various glomerulopathies, most notably membranous nephropathy. Less data are available regarding its use in idiopathic nephrotic syndrome (INS) secondary to minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS). We report here our experience with H.P. Acthar(®) Gel (repository corticotropin injection) as first-line or subsequent therapy in patients with INS. METHODS: Data were taken from three patients with MCD and ten patients with FSGS from around the US, who were treated with Acthar Gel as initial or subsequent therapy. Treatment was solely at the discretion of the primary nephrologist without a specific protocol. A complete response (CR) was defined as final urine protein-to-creatinine ratio <500 mg/g and a partial response (PR) as 50% decrease without rise of serum creatinine. Side effects and tolerability were noted. RESULTS: All three patients with MCD received Acthar Gel as second-line or later immunosuppressive (IS) therapy and all responded (one CR and two PRs). Two of the ten patients with FSGS received Acthar Gel as first-line IS therapy, while the other eight had failed multiple agents. Four of the ten patients with FSGS had responses, including two CRs and two PRs. The three patients with MCD tolerated therapy well without side effects. Five patients with FSGS tolerated therapy well, while five had various steroid-like side effects, resulting in therapy discontinuation in two patients. CONCLUSION: Acthar Gel is a viable alternative IS agent for treatment of INS in patients intolerant or resistant to conventional therapy. More data are needed to better define its appropriate place.

The Performance of Five Bioelectrical Impedance Analysis Prediction Equations against Dual X-ray Absorptiometry in Estimating Appendicular Skeletal Muscle Mass in an Adult Australian Population.

Appendicular skeletal muscle mass (ASM) is a diagnostic criterion for sarcopenia. Bioelectrical impedance analysis (BIA) offers a bedside approach to measure ASM but the performance of BIA prediction equations (PE) varies with ethnicities and body composition. We aim to validate the performance of five PEs in estimating ASM against estimation by dual-energy X-ray absorptiometry (DXA). We recruited 195 healthy adult Australians and ASM was measured using single-frequency BIA. Bland-Altman analysis was used to assess the predictive accuracy of ASM as determined by BIA against DXA. Precision (root mean square error (RMSE)) and bias (mean error (ME)) were calculated according to the method of Sheiner and Beal. Four PEs (except that by Kim) showed ASM values that correlated strongly with ASMDXA (r ranging from 0.96 to 0.97, p < 0.001). The Sergi equation performed the best with the lowest ME of -1.09 kg (CI: -0.84--1.34, p < 0.001) and the RMSE was 2.09 kg (CI: 1.72-2.47). In men, the Kyle equation performed better with the lowest ME (-0.32 kg (CI: -0.66-0.02) and RMSE (1.54 kg (CI: 1.14-1.93)). The Sergi equation is applicable in adult Australians (Caucasian) whereas the Kyle equation can be considered in males. The need remains to validate PEs in other ethnicities and to develop equations suitable for multi-frequency BIA.

Clinical Screening Tools for Sarcopenia and Its Management.

Sarcopenia, an age-related decline in muscle mass and function, is affecting the older population worldwide. Sarcopenia is associated with poor health outcomes, such as falls, disability, loss of independence, and mortality; however it is potentially treatable if recognized and intervened early. Over the last two decades, there has been significant expansion of research in this area. Currently there is international recognition of a need to identify the condition early for intervention and prevention of the disastrous consequences of sarcopenia if left untreated. There are currently various screening tools proposed. As yet, there is no consensus on the best tool. Effective interventions of sarcopenia include physical exercise and nutrition supplementation. This review paper examined the screening tools and interventions for sarcopenia.

Microbial analysis of in situ biofilm formation in drinking water distribution systems: implications for monitoring and control of drinking water quality.

Biofilm formation in drinking water distribution systems (DWDS) is influenced by the source water, the supply infrastructure and the operation of the system. A holistic approach was used to advance knowledge on the development of mixed species biofilms in situ, by using biofilm sampling devices installed in chlorinated networks. Key physico-chemical parameters and conventional microbial indicators for drinking water quality were analysed. Biofilm coverage on pipes was evaluated by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). The microbial community structure, bacteria and fungi, of water and biofilms was assessed using pyrosequencing. Conventional wisdom leads to an expectation for less microbial diversity in groundwater supplied systems. However, the analysis of bulk water showed higher microbial diversity in groundwater site samples compared with the surface water site. Conversely, higher diversity and richness were detected in biofilms from the surface water site. The average biofilm coverage was similar among sites. Disinfection residual and other key variables were similar between the two sites, other than nitrates, alkalinity and the hydraulic conditions which were extremely low at the groundwater site. Thus, the unexpected result of an exceptionally low diversity with few dominant genera (Pseudomonas and Basidiobolus) in groundwater biofilm samples, despite the more diverse community in the bulk water, is attributed to the low-flow hydraulic conditions. This finding evidences that the local environmental conditions are shaping biofilm formation, composition and amount, and hence managing these is critical for the best operation of DWDS to safeguard water quality.

Recovery from prolonged deep rocuronium-induced neuromuscular blockade: A randomized comparison of sugammadex reversal with spontaneous recovery.

BACKGROUND: Deep neuromuscular blockade (NMB) may not always be maintained to the end of surgery and the depth of block may be allowed to gradually diminish over time, particularly if reversal of NMB is not routinely performed. AIM: The current study aimed to assess recovery from deep rocuronium-induced NMB with sugammadex compared with placebo, provide data regarding the extent of residual blockade after deep rocuronium-induced NMB (placebo group), and to determine whether complete and reliable recovery could be provided by sugammadex (sugammadex group). MATERIALS AND METHODS: This was a randomized, placebo-controlled, safety-assessor-blinded study in adult patients of American Society of Anesthesiologists Class I to III. Patients with clinically relevant kidney or liver insufficiency were excluded. Anesthesia was administered as routinely practiced at each study site. Rocuronium 0.6 mg/kg was administered for intubation, with maintenance doses of 0.1-0.2 mg/kg as needed. After the last rocuronium dose, at deep NMB (target depth 1-2 post-tetanic counts), patients received a single dose of sugammadex 4.0 mg/kg or placebo as randomized. The primary endpoint was time from sugammadex or placebo administration to recovery of the train-of-four (TOF) ratio to 0.9. Safety was assessed through monitoring of adverse events, vital signs and physical examination. Patients were also assessed for evidence of residual or recurrence of NMB. With this design, the study will provide data regarding the extent of residual blockade under these conditions (placebo group), and determine whether complete and reliable recovery could be provided by sugammadex (sugammadex group). RESULTS: Recovery to a TOF ratio of ≥ 0.9 with sugammadex was significantly faster (~ 40 times) than spontaneous recovery: geometric mean (95 % confidence interval) times were 2.2 (1.9-2.5) and 89.8 (80.1-100.7) min, respectively (p < 0.0001, N = 134); maximum spontaneous recovery was 289.8 min. Safety was comparable between groups, with no recurrence of blockade. CONCLUSIONS: This study confirms a prolonged residual blockade in patients who did not receive sugammadex, with median time to recovery > 1.5 h in the placebo group and one patient taking 4.8 h to achieve a safe level of neuromuscular function recovery following deep NMB. In contrast, sugammadex provided complete and reliable recovery of neuromuscular function (median time to recovery of 2.0 min). Thus, deep NMB with rocuronium until the end of the operation may be possible in combination with sugammadex reversal.