Southern ocean carbon and heat impact on climate.

The Southern Ocean greatly contributes to the regulation of the global climate by controlling important heat and carbon exchanges between the atmosphere and the ocean. Rates of climate change on decadal timescales are therefore impacted by oceanic processes taking place in the Southern Ocean, yet too little is known about these processes. Limitations come both from the lack of observations in this extreme environment and its inherent sensitivity to intermittent processes at scales that are not well captured in current Earth system models. The Southern Ocean Carbon and Heat Impact on Climate programme was launched to address this knowledge gap, with the overall objective to understand and quantify variability of heat and carbon budgets in the Southern Ocean through an investigation of the key physical processes controlling exchanges between the atmosphere, ocean and sea ice using a combination of observational and modelling approaches. Here, we provide a brief overview of the programme, as well as a summary of some of the scientific progress achieved during its first half. Advances range from new evidence of the importance of specific processes in Southern Ocean ventilation rate (e.g. storm-induced turbulence, sea-ice meltwater fronts, wind-induced gyre circulation, dense shelf water formation and abyssal mixing) to refined descriptions of the physical changes currently ongoing in the Southern Ocean and of their link with global climate. This article is part of a discussion meeting issue 'Heat and carbon uptake in the Southern Ocean: the state of the art and future priorities'.

Cancer and Covid-19: Collectively catastrophic.

The Covid-19 pandemic has spread rapidly across the globe, resulting in more than 3 million deaths worldwide. The symptoms of Covid-19 are usually mild and non-specific, however in some cases patients may develop acute respiratory distress syndrome (ARDS) and systemic inflammation. Individuals with inflammatory or immunocompromising illnesses, such as cancer, are more susceptible to develop ARDS and have higher rates of mortality. This is mediated through an initial hyperstimulated immune response which results in elevated levels of pro-inflammatory cytokines and a subsequent cytokine storm. This potentiates positive feedback loops which are unable to be balanced by anti-inflammatory mediators. Therefore, elevated levels of IL-1ß, as a result of NLRP3 inflammasome activation, as well as IL-6 and TNF-α amongst many others, contribute to the progression of various cancer types. Furthermore, Covid-19 progression is associated with the depletion of CD8+ and CD4+ T cells, B cell and natural killer cell numbers. Collectively, a Covid-19-dependent pro-inflammatory profile and immune suppression promotes the optimal microenvironment for tumourigenesis, initiation and immune evasion of malignant cells, tumour progression and metastasis as well as cancer recurrence. There are, however, therapeutic windows of opportunity that may combat both Covid-19 and cancer to improve patient outcomes.

Non-vaccine serotype pneumococcal carriage in healthy infants in South Africa following introduction of the 13-valent pneumococcal conjugate vaccine.

BACKGROUND: Pneumococcal carriage studies provide a baseline for measuring the impact of pneumococcal conjugate vaccines (PCVs). The advent of conjugate vaccines has led to reductions in vaccine serotypes (VTs) in pneumococcal carriage. However, increasing non-vaccine serotypes (NVTs) remain a significant concern, necessitating continued surveillance of serotypes in the 13-valent PCV vaccine (PCV13) era. OBJECTIVES: To investigate pneumococcal carriage, serotype distribution and risk factors for pneumococcal colonisation among children presenting for routine immunisation at two clinics in Gauteng Province, South Africa (SA), 10 years after PCV introduction into the SA Expanded Programme on Immunisation (EPI-SA). METHODS: Nasopharyngeal swabs were collected from 322 healthy children aged between 6 weeks and 5 years at two clinic centres in 2014 and 2016. Demographic data, risk factors for colonisation and vaccination details were recorded. The pneumococcal isolates were serotyped and tested for antimicrobial susceptibility. RESULTS: Pneumococci were isolated from 138/316 healthy children (43.7%) presenting for routine immunisation at two clinics. The median age was 8.3 months and the age range 1.4 months - 5 years. Carriage varied across the age groups: 6 - 14 weeks 35.5%, 9 months 27.5%, 18 months 21.7%, and 5 years 15.2%. Risk factors significantly associated with pneumococcal colonisation included young age (9 - 18 months (odds ratio OR 3.5; 95% confidence interval (CI) 1.9 - 5.9), type of dwelling (single room (OR 8.1; 95% CI 1.3 - 52.3) or informal dwelling (OR 2.4; 95% CI 1.2 - 4.5)) and Haemophilus influenzae carriage (OR 5.6; 95% CI 0.6 - 2.5). Of the 26 serotypes detected, 19F (10/121; 8.3%) was the most frequent. The most frequent NVTs were 23B (16/121; 13.2%), 15B/C (14/121; 11.6 %) and 35B (11/121; 8.2%). Children aged 9 months carried the highest proportion of NVTs (33/101; 32.7%). Penicillin non-susceptibility was observed in 20 NVT isolates (20/36; 55.6%) and 2 VT isolates (2/36; 5.6%). CONCLUSIONS: The pneumococcal carriage prevalence described in our study varied across the age groups and was lower compared with other African studies that looked at pneumococcal carriage post PCV. The study gave insight into the common NVTs encountered at two immunisation clinics in Gauteng. Given that pneumococcal carriage precedes disease, common colonisers such as 15B/C and 35B may be sufficiently prevalent in carriage for expansion to result in significant disease replacement.

Molecular regulation of autophagy in a pro-inflammatory tumour microenvironment: New insight into the role of serum amyloid A.

Chronic inflammation, systemic or local, plays a vital role in tumour progression and metastasis. Dysregulation of key physiological processes such as autophagy elicit unfavourable immune responses to induce chronic inflammation. Cytokines, growth factors and acute phase proteins present in the tumour microenvironment regulate inflammatory responses and alter crosstalk between various signalling pathways involved in the progression of cancer. Serum amyloid A (SAA) is a key acute phase protein secreted by the liver during the acute phase response (APR) following infection or injury. However, cancer and cancer-associated cells produce SAA, which when present in high levels in the tumour microenvironment contributes to cancer initiation, progression and metastasis. SAA can activate several signalling pathways such as the PI3K and MAPK pathways, which are also known modulators of the intracellular degradation process, autophagy. Autophagy can be regarded as having a double edged sword effect in cancer. Its dysregulation can induce malignant transformation through metabolic stress which manifests as oxidative stress, endoplasmic reticulum (ER) stress and DNA damage. On the other hand, autophagy can promote cancer survival during metabolic stress, hypoxia and senescence. Autophagy has been utilised to promote the efficiency of chemotherapeutic agents and can either be inhibited or induced to improve treatment outcomes. This review aims to address the known mechanisms that regulate autophagy as well as illustrating the role of SAA in modulating these pathways and its clinical implications for cancer therapy.

Disparities in Breast Cancer: Private Patients Have Better Outcomes Than Public Patients.

INTRODUCTION: Different outcomes in breast cancer have been reported for low and high socio-economic groups. We present data quantifying disparities between South African public and private patients. METHODS: Records of 240 consecutive patients treated in 2008 in a public versus 97 patients in a private health facility were reviewed for demographic and oncologic data. RESULTS: The average of patients was 56.2 versus 51.9 years (p = 0.032). Stage at presentation was 0 in 0.83 versus 25.8%, I in 4.5 versus 15.5%, II in 41.3 versus 37.1%, III in 37.1 versus 18.6% and IV in 16.3 versus 3.1% public versus private patients. Seventy-three percent of patients were symptomatic versus 57.7%. Of patients with stage 0-III disease, 17.9 versus 20% had simple tumour excision and 7.5 versus 14%, oncoplastic tumour excision. The mastectomy rate was similar (52 vs. 60%), but immediate reconstruction was performed in 10 versus 63%. Public patients were less likely to have radiotherapy. The pathology was similar, 27.2 versus 20, 54 versus 52, 87 versus 61% of patients with stage I, II and III disease, respectively, had chemotherapy. Hormonal therapy for premenopausal patients in private was a LHRH agonist in 9.3%, ovarian ablation/BSO in 11.7% of public patients; biologicals were given in 7.2 versus 0% of patients. Overall survival for public versus private was 66 versus 80% (p < 0.001) months. Better per stage survival of private patients 100 versus 100, 72.7 versus 93.3, 84.8 versus 88.9, 57.3 versus 77.8 and 33 versus 33% for stages 0, I, II, III and IV, did not reach statistical significance. CONCLUSION: The greatest impact on outcome was stage at presentation, but more aggressive therapy for each stage resulted in a trend to better outcome for private patients.

An isolated outbreak of diphtheria in South Africa, 2015.

An outbreak of respiratory diphtheria occurred in two health districts in the province of KwaZulu-Natal in South Africa in 2015. A multidisciplinary outbreak response team was involved in the investigation and management of the outbreak. Fifteen cases of diphtheria were identified, with ages ranging from 4 to 41 years. Of the 12 cases that were under the age of 18 years, 9 (75%) were not fully immunized for diphtheria. The case fatality was 27%. Ninety-three household contacts, 981 school or work contacts and 595 healthcare worker contacts were identified and given prophylaxis against Corynebacterium diphtheriae infection. A targeted vaccination campaign for children aged 6-15 years was carried out at schools in the two districts. The outbreak highlighted the need to improve diphtheria vaccination coverage in the province and to investigate the feasibility of offering diphtheria vaccines to healthcare workers.

Decipher correlation patterns post prostatectomy: initial experience from 2 342 prospective patients.

BACKGROUND: Currently, there are multiple commercially available RNA-based biomarkers that are Medicare approved and suggested for use by the National Comprehensive Cancer Network guidelines. There is uncertainty as to which patients benefit from genomic testing and for whom these tests should be ordered. Here, we examined the correlation patterns of Decipher assay to understand the relationship between the Decipher and patient tumor characteristics. METHODS: De-identified Decipher test results (including Decipher risk scores and clinicopathologic data) from 2 342 consecutive radical prostatectomy (RP) patients tested between January and September 2015 were analyzed. For clinical testing, tumor specimen from the highest Gleason grade was sampled using a 1.5 mm tissue punch. Decipher scores were calculated based on a previously locked model. Correlations between Decipher score and clinicopathologic variables were computed using Spearman's rank correlation. Mixed-effect linear models were used to study the association of practice type and Decipher score. The significance level was 0.05 for all tests. RESULTS: Decipher score had a positive correlation with pathologic Gleason score (PGS; r=0.37, 95% confidence interval (CI) 0.34-0.41), pathologic T-stage (r=0.31, 95% CI 0.28-0.35), CAPRA-S (r=0.32, 95% CI 0.28-0.37) and patient age (r=0.09, 95% CI 0.05-0.13). Decipher reclassified 52%, 76% and 40% of patients in CAPRA-S low-, intermediate- and high-risk groups, respectively. We detected a 28% incidence of high-risk disease through the Decipher score in pT2 patients and 7% low risk in pT3b/pT4, PGS 8-10 patients. There was no significant difference in the Decipher score between patients from community centers and those from academic centers (P=0.82). CONCLUSIONS: Although Decipher correlated with baseline tumor characteristics for over 2 000 patients, there was significant reclassification of tumor aggressiveness as compared to clinical parameters alone. Utilization of the Decipher genomic classifier can have major implications in assessment of postoperative risk that may impact physician-patient decision making and ultimately patient management.

The clinical anatomy of cystic artery variations: a review of over 9800 cases.

PURPOSE: While laparoscopic cholecystectomy can be a routine procedure when biliary anatomy is normally located, cystic artery variations can easily disorientate the inexperienced surgeon to the anatomy of the hepatobiliary triangle. This study presents the clinically important anatomical variations of the cystic artery. METHODS: PubMed, Medline, Cochrane Database of Systematic Reviews, and Google Scholar databases were searched to conduct a review of the existing English literature on the clinically important cystic artery variations. An aberrant vessel was defined as a vessel that originated from an atypical source and/or one that was present in a specimen in addition to the normal vessel. RESULTS: The cystic artery originated typically from the right hepatic artery (79.02 %) and was found in the hepatobiliary triangle in only 5427 of 6661 (81.5 %) cases. Clinically important cystic artery variations are (1) the cystic artery located anterior to the common hepatic duct or common bile duct found in 485 of 2704 (17.9 %) and 228 of 4202 (5.4 %) of cases, respectively, (2) the cystic artery located inferior to the cystic duct found in 38 of 770 (4.9 %) of cases, (3) short cystic arteries found in 98 of 1037 (9.5 %) cases and (4) multiple cystic arteries found in (8.9 %) of cases. CONCLUSION: These variations are common in the general population and can lead to inadvertent ligation of biliary ducts or aberrant vessels. Therefore, it is important for the hepatobiliary surgeon to be aware of these vascular anomalies to avoid operative complications.

Use of transgenic oryzacystatin-I-expressing plants enhances recombinant protein production.

Plants are an effective and inexpensive host for the production of commercially interesting heterologous recombinant proteins. The Escherichia coli-derived glutathione reductase was transiently expressed as a recombinant model protein in the cytosol of tobacco plants using the technique of leaf agro-infiltration. Proteolytic cysteine protease activity progressively increased over time when glutathione reductase accumulated in leaves. Application of cysteine protease promoter-GUS fusions in transgenic tobacco identified a cysteine protease NtCP2 expressed in mature leaves and being stress responsive to be expressed as a consequence of agro-infiltration. Transgenic tobacco plants constitutively expressing the rice cysteine protease inhibitor oryzacystatin-I had significantly lower cysteine protease activity when compared to non-transgenic tobacco plants. Lower cysteine protease activity in transgenic plants was directly related to higher glutathione reductase activity and also higher glutathione reductase amounts in transgenic plants. Overall, our work has demonstrated as a novel aspect that transgenic tobacco plants constitutively expressing an exogenous cysteine protease inhibitor have the potential for producing more recombinant protein which is very likely due to the reduced activity of endogenous cysteine protease.

The effectiveness of continuous passive motion on range of motion, pain and muscle strength following rotator cuff repair: a systematic review.

OBJECTIVE: To systematically review the evidence on the effect of continuous passive motion, combined with usual physiotherapy management, on increasing shoulder joint range of motion and muscle strength, and reducing shoulder pain in adults following rotator cuff repair, compared with standard physiotherapy. DATA SOURCES: A comprehensive search in available bibliographic electronic databases was undertaken to locate eligible studies. Reference tracing was also used to locate studies. REVIEW METHODS: Randomized controlled trials reporting on the effect of continuous passive motion on increasing shoulder joint range of motion and muscle strength and reducing shoulder pain in adults following rotator cuff repair were included in the review. The PEDro scale was used to determine the methodological quality of the studies. Data were summarized in a narrative form because of their heterogeneity. RESULTS: Four randomized controlled trials were eligible for this review. One Japanese article was excluded as the text was unavailable in English. The methodological quality of the included studies averaged 7.67. Continuous passive motion was found to improve shoulder range of motion in two studies. One study found a decrease in pain in the intervention group and one study found that continuous passive motion improves muscle strength. CONCLUSION: Continuous passive motion is safe to use with physiotherapy treatment following rotator cuff repair surgery. It may help to prevent secondary complications post operatively.

Preliminary results on a study to locate the pterygopalatine fossa using mathematical formulae.

Blocking the contents of the pterygopalatine fossa (PPF) has been shown to be effective in treating most orofacial pain including that associated with trigeminal neuralgia. However, the technique is not widely used, and we propose it to be due to the vague descriptions of the techniques in the literature. The aim of this study was therefore to achieve an alternative method of locating the PPF. One hundred and sixty skulls from the department of Anatomy, University of Pretoria, were used. Distinct landmarks (both anthropometric and clinical) accompanied by existing and new anthropometric measurements were used to define the location of the PPF. Regression analysis was used to measure the reliability of predicting the location of the PPF. From the results, two mathematical formulae were devised (one for each side). These formulae were tested on 47 cadavers by inserting a needle at the calculated points after which the areas where dissected to determine whether or not the needle had entered the PPF. Our results showed an accuracy of 65.2% on the right and 54.4% on the left. In conclusion, improvement in the accuracy of the technique could aid in the management of various pain disorders as well as pain management during surgery.

Novel non-sense GCH1 mutation in a South African family diagnosed with dopa-responsive dystonia.

BACKGROUND: Dopa-responsive dystonia (DRD), a movement disorder characterized by onset in early childhood and a dramatic response to low doses of levodopa, has been shown to be caused by a number of different mutations in the GCH1 gene. METHODS: We identified a South African family which presented with DRD in three family members. Polymerase chain reaction (PCR) primers were designed to span all six exons of GCH1 and the PCR products were screened for pathogenic mutations using direct sequencing. RESULTS: A novel non-sense mutation (c.233delT; p.I78fsX79) was identified in the DRD patients, which would produce a markedly truncated protein of only 78 amino acids. This mutation was also present in a number of asymptomatic family members. CONCLUSIONS: A novel non-sense mutation in the GCH1 gene can be associated with DRD and reduced penetrance in South African patients.

The Relationship between Psychosocial Variables and Measures of Health Status in Fibromyalgia

Background: Fibromyalgia is considered to be a multifactorial condition in which a number of biological and psychological variables interact. However; the exact pathogenesis and effective treatment of fibromyalgia are still unknown. In this study the relationship between psychosocial variables of self-efficacy; helplessness; perceived social support; and pain-related beliefs and several measures of health status of patients with fibromyalgia were examined. Methods: Thirty-one patients diagnosed with fibromyalgia participated in the study. Patients diagnosed with concomitant rheumatological conditions were excluded from the study. Each patient was individually assessed by the same physician in terms of functional status and pain experience and then measured on psychosocial variables in a cross-sectional study. Correlations between these psychosocial and health status variables were calculated. Results: Significant correlations were found between the psychosocial variables and health status. Consistent with previous research; self-efficacy was found to be the most important psychosocial variable in the present study; correlating with several measures of health status. Quality of social support and cognitive beliefs hardly showed any relationship with health status. Conclusions: It is recommended that self-efficacy enhancement programmes be included in the treatment of patients with fibromyalgia. However; further research is still needed to investigate the effect of self-efficacy enhancement on the overall quality of life of these patients

Impact of conjugate Haemophilus influenzae type b (Hib) vaccine introduction in South Africa.

OBJECTIVE: To analyse trends in reported invasive Haemophilus influenzae disease in South Africa within the first five years of introduction of conjugate Haemophilus influenzae type b (Hib) vaccine in the routine child immunization schedule. METHODS: We used national laboratory-based surveillance data to identify cases of invasive H. influenzae disease between July 1999 and June 2004, and submitted isolates for serotyping and antimicrobial susceptibility testing. FINDINGS: The absolute number of Hib cases (reported to the national surveillance system) among children below one year of age decreased by 65%, from 55 cases in 1999-2000 to 19 cases in 2003-04. Enhanced surveillance initiated in 2003, identified human immunodeficiency virus (HIV)-infection and incomplete vaccination as contributing factors for Hib transmission. The total number of laboratory-confirmed cases of H. influenzae remained unchanged because non-type b disease was being increasingly reported to the surveillance system concomitant with system enhancements. Children with non-typable disease were more likely to be HIV-positive (32 of 34, 94%) than children with Hib disease (10 of 14, 71%), P = 0.051. Recent Hib isolates were more likely to be multidrug resistant (2% in 1999-2000 versus 19% in 2003-04, P = 0.001). CONCLUSION: Data from a newly established national laboratory-based surveillance system showed a decrease in Hib disease burden among South African children following conjugate vaccine introduction and identified cases of non-typable disease associated with HIV infection.

Avian exocrine secretions. I. Chemical characterization of the volatile fraction of the uropygial secretion of the green woodhoopoe, Phoeniculus purpureus.

Using gas chromatography-mass spectrometry in conjunction with auxiliary techniques such as solid phase microextraction and determination of double bond positions by means of dimethyl disulfide derivatization, 45 constituents of the uropygial secretion of the green woodhoopoe, Phoeniculus purpureus, have been identified. The majority of these constituents are long-chain branched and unbranched alkanes, and (Z)-alkenes such as (Z)-9-tricosene, and a number of unidentified wax esters. The more volatile fraction of the secretion contained short-chain fatty acids, aldehydes, aliphatic and heterocyclic aromatic amines, ketones, and dimethyl sulfides. This group of volatile compounds is responsible for the obnoxious odor of the secretion and also for its defensive action against predators.