DNA Copy Number Changes in <i>Schistosoma</i>-Associated and Non-<i>Schistosoma</i>-Associated Bladder Cancer

DNA copy number changes were investigated in 69 samples of schistosoma-associated (SA) and nonschistosoma-associated (NSA) squamous cell carcinoma (SCC) and transitional cell carcinoma (TCC) of the bladder by comparative genomic hybridization (CGH). DNA copy number changes were detected in 47 tumors. SA tumors had more changes than NSA tumors (mean, 7 vs. 4), whereas the number of changes in SCC and TCC tumors was similar. SA tumors displayed more gains than losses (1.7:1), whereas NSA tumors showed an equal number of gains and losses. Changes that were observed at similar frequencies in SCC and TCC, irrespective of the schistosomal status, included gains and high-level amplifications at 1q, 8q, and 20q and losses in 9p and 13q. These changes may be involved in a common pathway for bladder tumor development and progression independent of schistosomal status or histological subtype. Losses in 3p and gains at 5p were seen only in SCC (P < 0.01) and losses in 5q were more frequent in SA-SCC than in other tumors (P < 0.05). However, changes that were more frequent in TCC than those in SCC included gains at 17q (P < 0.01) and losses in 4q (P < 0.05) and 6q (P < 0.01). Gains and high-level amplifications at 5p were seen only in SASCC (P < 0.01), whereas gains and high-level amplifications with minimal common overlapping regions at 11q13 were more frequently seen both in SA-SCC and SA-TCC tumors (P < 0.01). In addition to the above mentioned alterations, several other changes were also seen at lower frequencies. The variations in the DNA copy number changes observed in TCC, SCC, SA, and NSA bladder carcinomas suggest that these tumors have different genetic pathways.Facultad de Ciencias Naturales y Muse

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Histological Findings from Controlled Application of a Thermal Plasma to Human Skin

Ionised gas or plasma is often described as the fourth state of matter since it can be produced from an electrically neutral gas which has been fully or partially ionised. The resulting mixture of free electrons, positively charged ions and un-ionized gas possess a rich chemistry and may be used to transport thermal energy. Plasma has thus found applications in such diverse fields as spacecraft propulsion, magnetic confinement fusion, silicon etching, and surface treatment and of course biomedicine. We have developed a plasma generating device that can deliver a controlled depth epidermal and dermal burn injury as a function of energy delivery over a unit area and time of exposure. This is important as a therapeutic tool for treating skin lesions; a device to create burn wound healing models, for medicolegal understanding of burn depth and for the development of new wound care products. In our study plasma is delivered onto a human skin model in an experiment approved by the local ethics committee. Fresh abdominoplasty skin was marked according to protocol and treated with a controlled energy dose per unit area using the new plasma delivery system developed at the Surrey Space Centre at Surrey University. Skin samples are biopsied and immediately placed in formal saline before sectioning and staining. The immediate histological changes of superficial burn injury in human skin can then be determined. The findings in this study show a reproducible depth of thermal injury as a function of energy delivery. Each 25 J/cm2 increment up to 100 J/cm2 causes a 0.5 mm depth of cutaneous thermal injury. In the 25 and 50 J/cm2 injury the epidermis remains intact and appears as a ‘first degree or superficial burn injury’. Histologically the basal epidermal cells show characteristic oedematous morphology which we have called ‘Frame Cells’ because the morphology after superficial injury has not been previously recognized. There is a clear line of demarcation within the superficial dermis where the zone of coagulation meets the zone of stasis. In the 75 and 100 J/cm2 the epidermis appears coagulated and has histologically separated from the dermis burn at the dermo-epidermoid junction. The line of dermal coagulative necrosis is clearly defined. Melanocytes are absent immediately after even the most superficial injury. Fibroblasts, vascular endothelial cells, epithelial cells, pigment cells, collagen and elastin are all examined using immunohistochemical stains

The In Vivo Pericapsular Tissue Response to Modern Polyurethane Breast Implants

Polyurethane breast implants were first introduced by Ashley (Plast Reconstr Surg 45:421–424, 1970), with the intention of trying to reduce the high incidence of capsular contracture associated with smooth shelled, high gel bleed, silicone breast implants. The sterilization of the polyurethane foam in the early days was questionable. More recently, ethylene oxide (ETO)-sterilized polyurethane has been used in the manufacturing process and this has been shown to reduce the incidence of biofilm. The improved method of attachment of polyurethane onto the underlying high cohesive gel, barrier shell layered, silicone breast implants also encourages bio-integration. Polyurethane covered, cohesive gel, silicone implants have also been shown to reduce the incidence of other problems commonly associated with smooth or textured silicone implants, especially with reference to displacement, capsular contracture, seroma, reoperation, biofilm and implant rupture. Since the introduction of the conical polyurethane implant (Silimed, Brazil) into the United Kingdom in 2009 (Eurosurgical, UK), we have had the opportunity to review histology taken from the capsules of polyurethane implants in three women ranging from a few months to over 3 years after implantation. All implants had been inserted into virgin subfascial, extra-pectoral planes. The results add to the important previously described histological findings of Bassetto et al. (Aesthet Plast Surg 34:481–485, 2010). Five distinct layers are identified and reasons for the development of each layer are discussed. Breast capsule around polyurethane implants, in situ for fifteen and 20 years, has recently been obtained and analysed in Brazil, and the histology has been incorporated into this study. After 20 years, the polyurethane is almost undetectable and capsular contracture may appear. These findings contribute to our understanding of polyurethane implant safety, and give reasoning for a significant reduction in clinical capsular contracture rate, up to 10 years after implantation, compared to contemporary silicone implants. A more permanent matrix equivalent to polyurethane may be the solution for reducing long-term capsular contracture