Calcific uraemic arteriolopathy (calciphylaxis) in patients on renal replacement therapy

Background. Calcific uraemic arteriolopathy (calciphylaxis) is an unusual and potentially fatal condition characterised by small-vessel calcification and ischaemic skin necrosis. It mainly affects patients with end-stage renal disease (ESRD) on haemodialysis, but may rarely occur in the absence of ESRD in conditions such as primary hyperparathyroidism, malignancy, alcoholic liver disease and connective tissue disease.Methods. We reviewed the records of all patients diagnosed with calciphylaxis while on renal replacement therapy at Tygerberg Hospital, Cape Town, South Africa, between 1990 and 2014, to describe its presentation, course and final outcome.Results. Nineteen patients developed calciphylaxis over this period. Their median age was 34 years and 13 (68.4%) were female. Fifteen (78.9%) had received a kidney transplant. All patients had painful skin lesions that rapidly progressed to infarction. Small-vessel calcification was seen on skin biopsy in 13 patients. Twelve patients had hyperparathyroidism. Several of the transplanted patients had been treated for graft rejection in the year preceding the diagnosis. Treatment consisted of good wound care and efforts to normalise serum calcium and phosphate levels. Five patients received an urgent parathyroidectomy. The outcome was fatal in 17 patients, with sepsis being the main cause of death.Conclusions. In our patients, calciphylaxis carried a worse prognosis than previously reported internationally. It should always be considered in the differential diagnosis of painful skin lesions in the dialysis or transplant patient

Rapid recovery of genetic diversity of stomatopod populations on Krakatau : temporal and spatial scales of marine larval dispersal

Author Posting. © Royal Society, 2002. This article is posted here by permission of Royal Society for personal use, not for redistribution. The definitive version was published in Proceedings of the Royal Society of London B 269 (2002): 1591-1597, doi:10.1098/rspb.2002.2026.Although the recovery of terrestrial communities shattered by the massive eruption of Krakatau in 1883 has been well chronicled, the fate of marine populations has been largely ignored. We examined patterns of genetic diversity in populations of two coral reef-dwelling mantis shrimp, Haptosquilla pulchella and Haptosquilla glyptocercus (Stomatopoda: Protosquillidae) , on the islands of Anak Krakatau and Rakata. Genetic surveys of mitochondrial cytochrome oxidase c (subunit 1) in these populations revealed remarkably high levels of haplotypic and nucleotide diversity that were comparable with undisturbed populations throughout the Indo-Pacific. Recolonization and rapid recovery of genetic diversity in the Krakatau populations indicates that larval dispersal from multiple and diverse source populations contributes substantially to the demographics of local populations over intermediate temporal (tens to hundreds of years) and spatial scales (tens to hundreds of kilometres). Natural experiments such as Krakatau provide an excellent mechanism to investigate marine larval dispersal and connectivity. Results from stomatopods indicate that marine reserves should be spaced no more than 50-100 km apart to facilitate ecological connectivity via larval dispersal.P.H.B. acknowledges support of a NSF Minority Postdoctoral Fellowship. Research was funded by grants to S.R.P. A Putnam grant supported fieldwork

The disruption of JEN1 from Candida albicans impairs the transport of lactate

A lactate permease was biochemically identified in Candida albicans RM1000 presenting the following kinetic parameters at pH 5.0: Km 0.33 ± 0.09 mM and Vmax 0.85± 0.06 nmol s-1 mg dry wt-1. Lactate uptake was competitively inhibited by pyruvic and propionic acids; acetic acid behaved as a non-competitive substrate. An ORF homologous to Saccharomyces cerevisiae gene JEN1 was identified (CaJEN1). Deletions of both CaJEN1 alleles of C. albicans (resulting strain CPK2) resulted in the loss of all measurable lactate permease activity. No CaJEN1 mRNA was detectable in glucose-grown cells neither activity for the lactate transporter. In a medium containing lactic acid, CaJEN1 mRNA was detected in the RM1000 strain, and no expression was found in cells of CPK2 strain. In a strain deleted in the CaCAT8 genes the expression of CaJEN1 was significantly reduced, suggesting the role of this gene as an activator for CaJEN1 expression. Both in C. albicans and in S. cerevisiae cells CaJEN1-GFP fusion was expressed and targeted to the plasma membrane. The native CaJEN1 was not functional in a S. cerevisiae jen1Δ strain. Changing ser217-CTG codon (encoding leucine in S. cerevisiae) to a TCC codon restored the permease activity in S. cerevisiae, proving that the CaJEN1 gene codes for a monocarboxylate transporter.Deutsche Forschungsgemeinschaft (SFB 579).Fundação para a Ciência e a Tecnologia (FCT) - Programa Operacional “Ciência, Tecnologia, Inovação” (POCTI) - POCTI/1999/BME/36625 (Eixo 2, Medida 2.3, QCAIII-FEDER) , SFRH/BD/4699/2001 , PRAXIS XXI/BD/18198/98

Extent of piriform cortex resection in children with temporal lobe epilepsy

OBJECTIVE: A greater extent of resection of the temporal portion of the piriform cortex (PC) has been shown to be associated with higher likelihood of seizure freedom in adults undergoing anterior temporal lobe resection (ATLR) for drug-resistant temporal lobe epilepsy (TLE). There have been no such studies in children, therefore this study aimed to investigate this association in a pediatric cohort. METHODS: A retrospective, neuroimaging cohort study of children with TLE who underwent ATLR between 2012 and 2021 was undertaken. The PC, hippocampal and amygdala volumes were measured on the preoperative and postoperative T1-weighted MRI. Using these volumes, the extent of resection per region was compared between the seizure-free and not seizure-free groups. RESULTS: In 50 children (median age 9.5 years) there was no significant difference between the extent of resection of the temporal PC in the seizure-free (median = 50%, n = 33/50) versus not seizure-free (median = 40%, n = 17/50) groups (p = 0.26). In a sub-group of 19 with ipsilateral hippocampal atrophy (quantitatively defined by ipsilateral-to-contralateral asymmetry), the median extent of temporal PC resection was greater in children who were seizure-free (53%) versus those not seizure-free (19%) (p = 0.009). INTERPRETATION: This is the first study demonstrating that, in children with TLE and hippocampal atrophy, more extensive temporal PC resection is associated with a greater chance of seizure freedom-compatible with an adult series in which 85% of patients had hippocampal sclerosis. In a combined group of children with and without hippocampal atrophy, the extent of PC resection was not associated with seizure outcome, suggesting different epileptogenic networks within this cohort

Leadership and early strategic response to the SARS-CoV-2 pandemic at a COVID-19 designated hospital in South Africa

While many countries are preparing to face the COVID-19 pandemic, the reported cases in Africa remain low. With a high burden of both communicable and non-communicable disease and a resource-constrained public healthcare system, sub-Saharan Africa is preparing for the coming crisis as best it can. We describe our early response as a designated COVID-19 provincial hospital in Cape Town, South Africa (SA).While the first cases reported were related to international travel, at the time of writing there was evidence of early community spread. The SAgovernment announced a countrywide lockdown from midnight 26 March 2020 to midnight 30 April 2020 to stem the pandemic and save lives. However, many questions remain on how the COVID-19 threat will unfold in SA, given the significant informal sector overcrowding and poverty in our communities. There is no doubt that leadership and teamwork at all levels is critical in influencing outcomes

Escape of SARS-CoV-2 501Y.V2 from neutralization by convalescent plasma

SARS-CoV-2 variants of concern (VOC) have arisen independently at multiple locations [1, 2] and may reduce the efficacy of current vaccines targeting the spike glycoprotein [3]. Here, using a live virus neutralization assay (LVNA), we compared neutralization of a non-VOC variant versus the 501Y.V2 variant using plasma collected from adults hospitalized with COVID-19 from two South African infection waves, with the second wave dominated by 501Y.V2 infections. Sequencing demonstrated that infections in first wave plasma donors were with viruses harbouring none of the 501Y.V2-defining mutations, except for one with the E484K mutation in the receptor binding domain. 501Y.V2 virus was effectively neutralized by plasma from second wave infections and first wave virus was effectively neutralized by first wave plasma. In cross-neutralization, 501Y.V2 virus was poorly neutralized by first wave plasma, with a 15.1-fold drop relative to 501Y.V2 neutralization by second wave plasma across participants. In contrast, second wave plasma cross-neutralization of first wave virus was more effective, showing only a 2.3-fold decline relative to first wave plasma neutralization of first wave virus. While we only tested one plasma elicited by E484K alone, this potently neutralized both variants. The observed effective neutralization of first wave virus by 501Y.V2 infection elicited plasma provides preliminary evidence that vaccines based on VOC sequences could retain activity against other circulating SARS-CoV-2 lineages

SARS-CoV-2 prolonged infection during advanced HIV disease evolves extensive immune escape

Characterizing SARS-CoV-2 evolution in specific geographies may help predict properties of the variants that come from these regions. We mapped neutralization of a SARS-CoV-2 strain that evolved over 6 months from ancestral virus in a person with advanced HIV disease in South Africa; this person was infected prior to emergence of the Beta and Delta variants. We longitudinally tracked the evolved virus and tested it against self-plasma and convalescent plasma from ancestral, Beta, and Delta infections. Early virus was similar to ancestral, but it evolved a multitude of mutations found in Omicron and other variants. It showed substantial but incomplete Pfizer BNT162b2 escape, weak neutralization by self-plasma, and despite pre-dating Delta, it also showed extensive escape of Delta infection-elicited neutralization. This example is consistent with the notion that SARS-CoV-2 evolving in individual immune-compromised hosts, including those with advanced HIV disease, may gain immune escape of vaccines and enhanced escape of Delta immunity, and this has implications for vaccine breakthrough and reinfections

HIV status alters disease severity and immune cell responses in Beta variant SARS-CoV-2 infection wave

There are conflicting reports on the effects of HIV on COVID-19. Here, we analyzed disease severity and immune cell changes during and after SARS-CoV-2 infection in 236 participants from South Africa, of which 39% were people living with HIV (PLWH), during the first and second (Beta dominated) infection waves. The second wave had more PLWH requiring supplemental oxygen relative to HIV-negative participants. Higher disease severity was associated with low CD4 T cell counts and higher neutrophil to lymphocyte ratios (NLR). Yet, CD4 counts recovered and NLR stabilized after SARS-CoV-2 clearance in wave 2 infected PLWH, arguing for an interaction between SARS-CoV-2 and HIV infection leading to low CD4 and high NLR. The first infection wave, where severity in HIV negative and PLWH was similar, still showed some HIV modulation of SARS-CoV-2 immune responses. Therefore, HIV infection can synergize with the SARS-CoV-2 variant to change COVID-19 outcomes