Synthesis and Bioactivity of Reduced Chalcones Containing Sulfonamide Side Chains.

The effect on the bioactivity of antibacterial sulfonamide drugs against malaria and tuberculosis via an increase of the lipid solubility groups by condensation with a reduced chalcone was investigated. Sulfonamide derivatives (8a-8d) were obtained via a 1,3-diarylpropane scaffold, prepared by reduction of the relevant chalcones, followed by the addition of a sulfonamide moiety via the Mannich and the Mannich exchange reactions. The ClogP values indicated that the lipophilicities of 8a-8d and intermediate reduced chalcones and N-alkylated reduced chalcones (5a-7a) were much higher than those of the sulfonamides (1a-1c). The N-alkylated reduced chalcone derivatives 6 and 7 exhibited the highest antimalarial (Plasmodium falciparum (NF54 strain)) activity. Addition of the sulfonamide group weakened the activity, even though some ClogP values were higher, while 1a-1c showed no activity. The reduced chalcones 5a and 5 showed potent growth inhibition of Mycobacterium tuberculosis (H37Rv strain), but the sulfonamide derivatives 8a and 8d showed no or insignificant activity (0 and 14%, respectively) against M. tuberculosis, despite high ClogP values. Thus, the possible increase in bioactivity expected from an increase in ClogP values (lipophilicity) might be counteracted by the higher molecular weight of the studied analogues.

The development of a nurse-led preoperative anaesthesia screening tool by Delphi consensus.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Long-term HIV and tuberculosis outcomes in patients hospitalised with severe cutaneous adverse reactions.

Background: Treatment-limiting severe cutaneous adverse reactions (SCAR) occur more commonly amongst persons with HIV-associated tuberculosis (TB). The impact of SCAR on long-term HIV/TB outcomes is unknown. Methods: Patients with TB and/or HIV admitted to Groote Schuur Hospital, Cape Town, South Africa with SCAR between 1/10/2018 and 30/09/2021 were eligible. Follow-up data was collected for 6- and 12-month outcomes: mortality, TB and antiretroviral therapy (ART) regimen changes, TB treatment completion, and CD4 count recovery. Results: Forty-eight SCAR admissions included: 34, 11, and 3 HIV-associated TB, HIV-only and TB-only patients with 32, 13 and 3 cases of drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome/toxic epidermal necrolysis and generalised bullous fixed-drug eruption respectively. Nine (19%), all HIV-positive (eight co-infected with TB), were deceased at 12-months, and 12(25%) were lost to follow-up. Amongst TB-SCAR patients, seven (21%) were discharged on all four first-line anti-TB drugs (FLTD), while 12(33%) had regimens with no FLTDs; 24/37(65%) completed TB treatment. Amongst HIV-SCAR patients, 10/31(32%) changed ART regimen. If retained in care (24/36), median (IQR) CD4 counts increased at 12-months post-SCAR (115(62-175) vs. 319(134-439) cells/uL). Conclusion: SCAR admission amongst patients with HIV-associated TB results in substantial mortality, and considerable treatment complexity. However, if retained in care, TB regimens are successfully completed, and immune recovery is good despite SCAR.

Low mortality of people living with diabetes mellitus diagnosed with COVID-19 and managed at a field hospital in Western Cape Province, South Africa.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) was declared an international pandemic by the World Health Organization in March 2020. Throughout the pandemic, the association between diabetes mellitus (DM) and more severe COVID-19 has been well described internationally, with limited data, however, on South Africa (SA). The role of field hospitals in the management of patients with COVID-19 in SA has not yet been described. OBJECTIVES: To describe the mortality and morbidity of people living with DM (PLWD) and comorbid COVID-19, as well as to shed light on the role of intermediate facilities in managing DM and COVID-19 during the pandemic. METHODS: This is a single-centre cross-sectional descriptive study that included all patients with confirmed COVID-19 and pre-existing or newly diagnosed DM (of any type) admitted to the Cape Town International Convention Centre (CTICC) Intermediate Care Bed Facility from June 2020 to August 2020. This study presents the profile of patients admitted to the CTICC, and reports on the clinical outcome of PLWD diagnosed with COVID-19, and additionally determines some associations between risk factors and death or escalation of care in this setting. RESULTS: There were 1 447 admissions at the CTICC, with a total of 674 (46.6%) patients who had confirmed DM, of whom 125 (19%) were newly diagnosed diabetics and 550 (81%) had pre-existing DM. Included in this group were 57 referrals from the telemedicine platform - a platform that identified high-risk diabetic patients with COVID-19 in the community, and linked them directly to hospital inpatient care. Of the 674 PLWD admitted, 593 were discharged alive, 45 were escalated to tertiary hospital requiring advanced care and 36 died. PLWD who died were older, had more comorbidities (specifically chronic obstructive pulmonary disease, congestive cardiac failure and chronic kidney disease) and were more likely to be on insulin. CONCLUSIONS: In a resource-limited environment, interdisciplinary and interfacility collaboration ensured that complicated patients with DM and COVID-19 were successfully managed in a field hospital setting. Telemedicine offered a unique opportunity to identify high-risk patients in the community and link them to in-hospital monitoring and care. Future studies should explore ways to optimise this collaboration, as well as to explore possibilities for early identification and management of high-risk patients.

South African cardiovascular risk stratification guideline for non-cardiac surgery.

Executive summary The South African (SA) guidelines for cardiac patients for non-cardiac surgery were developed to address the need for cardiac risk assessment and risk stratification for elective non-cardiac surgical patients in SA, and more broadly in Africa.The guidelines were developed by updating the Canadian Cardiovascular Society Guidelines on Perioperative Cardiac Risk Assessment and Management for Patients Who Undergo Non-cardiac Surgery, with a search of literature from African countries and recent publications. The updated proposed guidelines were then evaluated in a Delphi consensus process by SA anaesthesia and vascular surgical experts. The recommendations in these guidelines are:1. We suggest that elective non-cardiac surgical patients who are 45 years and older with either a history of coronary artery disease, congestive cardiac failure, stroke or transient ischaemic attack, or vascular surgical patients 18 years or older with peripheral vascular disease require further preoperative risk stratification as their predicted 30-day major adverse cardiac event (MACE) risk exceeds 5% (conditional recommendation: moderate-quality evidence).2. We do not recommend routine non-invasive testing for cardiovascular risk stratification prior to elective non-cardiac surgery in adults (strong recommendation: low-to-moderate-quality evidence).3. We recommend that elective non-cardiac surgical patients who are 45 years and older with a history of coronary artery disease, or stroke or transient ischaemic attack, or congestive cardiac failure or vascular surgical patients 18 years or older with peripheral vascular disease should have preoperative natriuretic peptide (NP) screening (strong recommendation: high-quality evidence).4. We recommend daily postoperative troponin measurements for 48 - 72 hours for non-cardiac surgical patients who are 45 years and older with a history of coronary artery disease, or stroke or transient ischaemic attack, or congestive cardiac failure or vascular surgical patients 18 years or older with peripheral vascular disease, i.e. (i) a baseline risk >5% for MACE 30 days after elective surgery (if no preoperative NP screening), or (ii) an elevated B-type natriuretic peptide (BNP)/N-terminal-prohormone B-type natriuretic peptide (NT-proBNP) measurement before elective surgery (defined as BNP >99 pg/mL or a NT-proBNP >300 pg/mL) (conditional recommendation: moderate-quality evidence).Additional recommendations are given for the management of myocardial injury after non-cardiac surgery (MINS) and medications for comorbidities.

A proposed selection index for feedlot profitability based on estimated breeding values.

It is generally accepted that feed intake and growth (gain) are the most important economic components when calculating profitability in a growth test or feedlot. We developed a single post-weaning growth (feedlot) index based on the economic values of different components. Variance components, heritabilities and genetic correlations for and between initial weight (IW), final weight (FW), feed intake (FI), and shoulder height (SHD) were estimated by multitrait restricted maximum likelihood procedures. The estimated breeding values (EBVs) and the economic values for IW, FW and FI were used in a selection index to estimate a post-weaning or feedlot profitability value. Heritabilities for IW, FW, FI, and SHD were 0.41, 0.40, 0.33, and 0.51, respectively. The highest genetic correlations were 0.78 (between IW and FW) and 0.70 (between FI and FW). EBVs were used in a selection index to calculate a single economical value for each animal. This economic value is an indication of the gross profitability value or the gross test value (GTV) of the animal in a post-weaning growth test. GTVs varied between -R192.17 and R231.38 with an average of R9.31 and a standard deviation of R39.96. The Pearson correlations between EBVs (for production and efficiency traits) and GTV ranged from -0.51 to 0.68. The lowest correlation (closest to zero) was 0.26 between the Kleiber ratio and GTV. Correlations of 0.68 and -0.51 were estimated between average daily gain and GTV and feed conversion ratio and GTV, respectively. These results showed that it is possible to select for GTV. The selection index can benefit feedlotting in selecting offspring of bulls with high GTVs to maximize profitability.

A genetic analysis of post-weaning feedlot performance and profitability in Bonsmara cattle.

The aim of this study was to identify factors influencing profitability in a feedlot environment and to estimate genetic parameters for and between a feedlot profit function and productive traits measured in growth tests. The heritability estimate of 0.36 for feedlot profitability shows that this trait is genetically inherited and that it can be selected for. The genetic correlations between feedlot profitability and production and efficiency varied from negligible to high. The genetic correlation estimate of -0.92 between feed conversion ratio and feedlot profitability is largely due to the part-whole relationship between these two traits. Consequently, a multiple regression equation was developed to estimate a feed intake value for all performance-tested Bonsmara bulls, which were group fed and whose feed intakes were unknown. These predicted feed intake values enabled the calculation of a post-weaning growth or feedlot profitability value for all tested bulls, even where individual feed intakes were unknown. Subsequently, a feedlot profitability value for each bull was calculated in a favorable economic environment, an average economic environment and in an unfavorable economic environment. The high Pearson and Spearman correlations between the estimate breeding values based on the average economic environment and the other two environments suggested that the average economic environment could be used to calculate estimate breeding values for feedlot profitability. It is therefore not necessary to change the carcass, weaned calf or feed price on a regular basis to allow for possible re-rankings based on estimate breeding values.

Structural characterization of oligosaccharides in the milk of an African elephant (Loxodonta africana africana).

The oligosaccharides present in the milk of an African elephant (Loxodonta africana africana), collected 4 days post partum, were separated by size exclusion-, anion exchange- and high-performance liquid chromatography (HPLC) before characterisation by (1)H NMR spectroscopy. Neutral and acidic oligosaccharides were identified. Neutral oligosaccharides characterised were isoglobotriose, Gal(beta1-4)[Fuc(alpha1-3)]GlcNAc(beta1-3)Gal(beta1-4)Glc, Gal(beta1-4)[Fuc(alpha1-3)]GlcNAc(beta1-3)Gal(beta1-4)[Fuc(alpha1-3)]GlcNAc(beta1-3)Gal(beta1-4)Glc, Gal(alpha1-3)Gal(beta1-4)[Fuc(alpha1-3)]GlcNAc(beta1-3)Gal(beta1-4)Glc and a novel oligosaccharide that has not been reported in the milk or colostrum of any other mammal: Gal(alpha1-3)Gal(beta1-4)[Fuc(alpha1-3)]GlcNAc(beta1-3)Gal(beta1-4)[Fuc(alpha1-3)]GlcNAc(beta1-3)Gal(beta1-4)Glc. Acidic oligosaccharides that are also found in the milk of Asian elephant were Neu5Ac(alpha2-3)Gal(beta1-4)Glc, Neu5Ac(alpha2-6)Gal(beta1-4)Glc, Neu5Ac(alpha2-3)Gal(beta1-4)[Fuc(alpha1-3)]Glc, Neu5Ac(alpha2-6)Gal(beta1-4)GlcNAc(beta1-3)Gal(beta1-4)Glc, Neu5Ac(alpha2-3)Gal(beta1-4)[Fuc(alpha1-3)]GlcNAc(beta1-3)Gal(beta1-4)Glc, Neu5Ac(alpha2-6)Gal(beta1-4)GlcNAc(beta1-3)Gal(beta1-4)[Fuc(alpha1-3)]GlcNAc(beta1-3)Gal(beta1-4)Glc and Neu5Ac(alpha2-6)Gal(beta1-4)GlcNAc(beta1-3){Gal(alpha1-3)Gal(beta1-4)[Fuc(alpha1-3)]GlcNAc(beta1-6)}Gal(beta1-4)Glc, while Neu5Gc(alpha2-3)Gal(beta1-4)Glc, Neu5Ac(alpha2-6)Gal(beta1-4)GlcNAc(beta1-3)Gal(beta1-4)[Fuc(alpha1-3)]Glc, Neu5Ac(alpha2-6)Gal(beta1-4)GlcNAc(beta1-3)[Gal(beta1-4)GlcNAc(beta1-6)]Gal(beta1-4)Glc and Neu5Ac(alpha2-6)Gal(beta1-4)GlcNAc(beta1-3){Gal(beta1-4)[Fuc(alpha1-3)]GlcNAc(beta1-6)}Gal(beta1-4)Glc have not been found in Asian elephant milk. The oligosaccharides characterised contained both alpha(2-3)- and alpha(2-6)-linked Neu5Ac residues. They also contain only the type II chain, as found in most non-human, eutherian mammals.

Correlation between histopathology and linoleic acid levels in five meningioma types.

The total fatty acid compositions of neoplastic tissues in 5 different meningioma types (meningotheliomatous, transitional, vascular, fibroblastic, atypical), analysed by gas-liquid chromatography, are presented in correlation with their histopathology. The benign meningioma types (first 3) had higher relative percentages of linoleic acid, compared to the apparently malignant meningioma types (fibroblastic, atypical). From these results it is suggested that a high relative percentage of linoleic acid is characteristic of benign neoplastic growth, while a low relative percentage may correlate with increased malignancy.

Cervical intervertebral disc prolapse associated with traumatic facet dislocations.

Closed reduction of dislocated facet joints is considered safe by most authors. We report the occurrence of traumatic cervical disc prolapse associated with these injuries in four patients. Without adequate radiological exclusion of this pathology, reduction may have catastrophic consequences as illustrated by two of our cases. Anterior discectomy and open reduction and fixation provide safe and successful avenues of treatment.

Randomised controlled trial comparing oral and intravenous paracetamol (acetaminophen) plasma levels when given as preoperative analgesia.

Gastric absorption of oral paracetamol (acetaminophen) may be unreliable perioperatively in the starved and stressed patient. We compared plasma concentrations of parenteral paracetamol given preoperatively and oral paracetamol when given as premedication. Patients scheduled for elective ear; nose and throat surgery or orthopaedic surgery were randomised to receive either oral or intravenous paracetamol as preoperative medication. The oral dose was given 30 minutes before induction of anaesthesia and the intravenous dose given pre-induction. All patients were given a standardised anaesthetic by the same specialist anaesthetist who took blood for paracetamol concentrations 30 minutes after the first dose and then at 30 minute intervals for 240 minutes. Therapeutic concentrations of paracetamol were reached in 96% of patients who had received the drug parenterally, and 67% of patients who had received it orally. Maximum median plasma concentrations were 19 mg.l(-1) (interquartile range 15 to 23 mg.l(-1)) and 13 mg.l(-1) (interquartile range 0 to 18 mg.l(-1)) for the intravenous and oral group respectively. The difference between intravenous and oral groups was less marked after 150 minutes but the intravenous preparation gave higher plasma concentrations throughout the study period. It can be concluded that paracetamol gives more reliable therapeutic plasma concentrations when given intravenously.

Taxonomic relationships of Cryptococcus and Tremella based on fatty acid composition and other phenotypic characters.

The cellular long-chain fatty acids present in 33 strains, representing 15 species of Cryptococcus, and 4 species of Tremella, were determined by gas chromatography. According to the relative amounts of fatty acid methyl esters, the Cryptococcus species studied were divided into four main groups. Possible relationships between species representing the two genera are presented in a new model, where cellular long-chain fatty acid compositions and other phenotypic characteristics are included.

Molecular and functional roles of duodenal cytochrome B (Dcytb) in iron metabolism.

Dcytb has been identified as the mammalian transplasma ferric reductase that catalyzes the reduction of ferric to ferrous iron in the process of iron absorption. Its mRNA and protein levels are up-regulated by several independent stimulators of iron absorption. Furthermore, its cDNA encodes putative binding sites for heme and ascorbic acid. Using Northern and Western blots, RT-PCR and confocal microscopy, we studied the expression and localisation of Dcytb in cell lines and tissues of CD1 mice. Dcytb expression and function were modulated by iron. Dcytb and DMT1, both predominantly localised in the apical region of the duodenum were up-regulated in iron deficiency. Dcytb, the iron regulated ferric reductase may also utilize cytoplasmic ascorbate as electron donor for transmembrane reduction of iron. Dcytb expression was found in other tissues apart from the duodenum and its regulation and functions at these other sites are of interest in iron metabolism.