Repurposing BCL-2 and Jak 1/2 inhibitors: Cure and treatment of HIV-1 and other viral infections.

B cell lymphoma 2 (BCL-2) family proteins are involved in the mitochondrial apoptotic pathway and are key modulators of cellular lifespan, which is dysregulated during human immunodeficiency virus type 1 (HIV-1) and other viral infections, thereby increasing the lifespan of cells harboring virus, including the latent HIV-1 reservoir. Long-lived cells harboring integrated HIV-1 DNA is a major barrier to eradication. Strategies reducing the lifespan of reservoir cells could significantly impact the field of cure research, while also providing insight into immunomodulatory strategies that can crosstalk to other viral infections.

Targeting Macrophage Dysregulation for Viral Infections: Novel Targets for Immunomodulators.

A major barrier to human immunodeficiency virus (HIV-1) cure is the latent viral reservoir, which persists despite antiretroviral therapy (ART), including across the non-dividing myeloid reservoir which is found systemically in sanctuary sites across tissues and the central nervous system (CNS). Unlike activated CD4+ T cells that undergo rapid cell death during initial infection (due to rapid viral replication kinetics), viral replication kinetics are delayed in non-dividing myeloid cells, resulting in long-lived survival of infected macrophages and macrophage-like cells. Simultaneously, persistent inflammation in macrophages confers immune dysregulation that is a key driver of co-morbidities including cardiovascular disease (CVD) and neurological deficits in people living with HIV-1 (PLWH).

Ischaemic breast necrosis following coronary artery bypass grafting using left internal mammary artery: understanding the risks.

Background: Coronary artery bypass grafting (CABG) is a common procedure performed commonly using left internal mammary artery (LIMA). We report a case of sternal wound dehiscence and breast necrosis following LIMA harvest in a 55-year-old obese lady with macromastia, diabetes mellitus, hypertension and end stage renal disease requiring dialysis. We also review the existing literature.

Burns infection profile of Singapore: prevalence of multidrug-resistant Acinetobacter baumannii and the role of blood cultures.

Background: With various changes implemented such as perioperative antibiotics for tangential excision, this retrospective study reviews the infection profile of burn patients at Singapore's only centralized burns unit. Worldwide, the appearance of multidrug-resistant (MDR) strains of Acinetobacter baumannii (A. baumannii) continues to worsen patient outcomes.

Breast cancer resistance protein identifies clonogenic keratinocytes in human interfollicular epidermis.

Introduction: There is a practical need for the identification of robust cell-surface markers that can be used to enrich for living keratinocyte progenitor cells. Breast cancer resistance protein (ABCG2), a member of the ATP binding cassette (ABC) transporter family, is known to be a marker for stem/progenitor cells in many tissues and organs.

Methods: We investigated the expression of ABCG2 protein in normal human epidermis to evaluate its potential as a cell surface marker for identifying and enriching for clonogenic epidermal keratinocytes outside the pilosebaceous tract.

Systematic review of seat-belt trauma to the female breast: a new diagnosis and management classification.

Background: Legislation, education and technology have led to a rise in the use of seat belts. This has significantly reduced automobile accident-related mortality, but it has increased seat belt-associated injuries. The aim of this study was to review all publications on seat-belt injury to the female breast and to analyse patterns of presentation, management and outcomes.

Hypertrophic scars and keloids in surgery: current concepts.

Hypertrophic scars and keloids remain a challenge in surgery. We appreciate that our understanding of the process at cellular and molecular level, profound as it is, when it comes to the clinical evidence much is left to be desired. Although the bench to bedside conundrum remains, the science of translational research calls for an even higher level of cooperation between the scientist and the clinician for the impetus to succeed.

Characterization of early thermal burns and the effects of hyperbaric oxygen treatment: a pilot study.

Background And Aims: Studies investigating hyperbaric oxygen treatment (HBOT) to improve outcome in burns have been inconclusive. In this study, we aimed to characterize early thermal burns injury in adult patients with < 40% total body surface area (TBSA) and to determine the effects of HBOT administered within 24 h to 48 h of a burn injury.

Methods: Seventeen subjects were randomized into control (n = 9) and HBOT treatment (n = 8) arms.

Decellularized porcine saphenous artery for small-diameter tissue-engineered conduit graft.

Decellularized xenografts have been identified as potential scaffolds for small-diameter vascular substitutes. This study aimed to develop and investigate a biomechanically functional and biocompatible acellular conduit using decellularized porcine saphenous arteries (DPSAs), through a modified decellularization process using Triton X-100/NH4 OH solution and serum-containing medium. Histological and biochemical analysis indicated a high degree of cellular removal and preservation of the extracellular matrix.

Human tissues contain CD141hi cross-presenting dendritic cells with functional homology to mouse CD103+ nonlymphoid dendritic cells.

Dendritic cell (DC)-mediated cross-presentation of exogenous antigens acquired in the periphery is critical for the initiation of CD8(+) T cell responses. Several DC subsets are described in human tissues but migratory cross-presenting DCs have not been isolated, despite their potential importance in immunity to pathogens, vaccines, and tumors and tolerance to self. Here, we identified a CD141(hi) DC present in human interstitial dermis, liver, and lung that was distinct from the majority of CD1c(+) and CD14(+) tissue DCs and superior at cross-presenting soluble antigens.

Homograft banking in Singapore: two years of cardiovascular tissue banking in Southeast Asia.

Established in 2008, the National Cardiovascular Homograft Bank (NCHB) has been instrumental in creating an available supply of cardiovascular tissues for implantation in Singapore. This article introduces its collaboration with Singapore General Hospital Skin Bank Unit. The procedure of homograft recovery, processing, cryopreservation and quality assurance are presented.

Keloid fibroblasts are more sensitive to Wnt3a treatment in terms of elevated cellular growth and fibronectin expression.

Background: Current evidence suggests the potential role of Wnt signalling in keloids pathogenesis but such literature remains scanty. We hypothesize that Wnt signalling is upregulated in keloid fibroblasts (KFs) and this promotes cellular growth, migration and extracellular matrix (ECM) production in such fibroblasts.

Objectives: To verify the downregulation of secreted frizzled-related protein 1 (SFRP1), a Wnt inhibitor and test KFs sensitivity to Wnt3a treatment compared to NFs in terms of activation of Wnt/β-catenin, cellular growth, migration and ECM expressions.

The role of R-spondin2 in keratinocyte proliferation and epidermal thickening in keloid scarring.

Keloids are found only in humans and the underlying biochemical mechanisms of their pathogenesis remain unknown. R-spondins (Rspos) are a relatively new group of secreted proteins known to be Wnt/β-catenin signaling agonists, but their role in keloids has yet to be elucidated. We investigated the expression levels of R-spondin2 (Rspo2) in cell lysates and conditioned media of monocultures and co-cultures of fibroblasts and keratinocytes derived from keloids and normal skin.

Modifications of the radial forearm flap phalloplasty for female-to-male gender reassignment.

The radial forearm flap remains the preferred technique for phalloplasty. From 1999 to 2009, 19 patients with primary female transsexualism underwent gender reassignment surgery at our center. The radial forearm flap phalloplasty is modified as a two-stage procedure, with prelamination of the neourethra on the donor forearm before microsurgical transfer 3 months later.

The fibula osteoseptocutaneous flap incorporating the hemisoleus muscle for complex head and neck defects: anatomical study and clinical applications.

Background: In patients with extensive bone and soft-tissue defects, the inclusion of the hemisoleus muscle with the fibula osteoseptocutaneous flap would provide the needed soft-tissue volume to the flap. This study evaluates the reliability and technical considerations for the inclusion of the hemisoleus with the fibula and skin paddle as a chimeric, peroneal artery-based flap.

Methods: The location and size of major arterial branches of the peroneal artery supplying the lateral hemisoleus muscle were investigated in 10 cadaveric injected lower limb specimens.

The use of Urgotul in the treatment of partial thickness burns and split-thickness skin graft donor sites: a prospective control study.

The use of paraffin-impregnated gauze for burns and skin graft donor sites is commonly associated with wound adherence with consequent pain and trauma upon removal. This prospective clinical study was performed to evaluate a new class of lipido-colloid dressings (Urgotul) in promoting healing and in reducing tissue adherence. In a 6-month period, 25 consecutive patients were recruited.

Use of the microdebrider for treatment of fibrous gynaecomastia.

Background: In the quest for reduced scars and better aesthetic outcomes in minimally invasive surgical techniques for gynaecomastia, suction-assisted lipoplasty and ultrasound-assisted lipoplasty are now considered accepted recent advancements. Nevertheless, the fibrous glandular breast disc encountered in young, thin patients requires a separate peri-areolar incision as the disc cannot be removed with suction lipoplasty. The use of a microdebrider (powered shaving rotary device) is a potential solution to this problem.

Ehlers-Danlos syndrome associated with cleft lip and palate.

Ehlers-Danlos syndrome (EDS) is a hereditary connective tissue disorder caused by abnormal collagen synthesis and presents with classic features of hyperextensibility, fragility of skin and joint hypermobility. It has not been commonly described as being associated with cleft lip and/or palate, and a literature search has disclosed only one case (1984) of type IV EDS with cleft lip and palate. The authors have seen another case of EDS associated with cleft lip and palate.

Use of tissue sealants in face-lifts: a metaanalysis.

Background: This review sought to determine the efficacy of tissue sealants such as fibrin tissue adhesives and platelet-rich plasma in reducing postoperative drainage, ecchymosis, and edema after face-lift surgery.

Methods: The electronic databases MEDLINE (1966-May 2007) and EMBASE (1974-May 2007) and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched for human studies, randomized controlled trials, controlled clinical trials, metaanalyses, and reviews of randomized controlled trials using the key words "fibrin tissue adhesive," "tissue sealant," "platelet-rich plasma," "face-lift," "rhytidoplasty," "rhytidectomy," and "facial plastic surgery." The search yielded 10 articles, only 3 of which met our inclusion criteria.

Topical negative pressure wound therapy: a review of its role and guidelines for its use in the management of acute wounds.

Over the past two decades, topical negative pressure (TNP) wound therapy has gained wide acceptance as a genuine strategy in the treatment algorithm for a wide variety of acute and chronic wounds. Although extensive experimental and clinical evidence exists to support its use and despite the recent emergence of randomised control trials, its role and indications have yet to be fully determined. This article provides a qualitative overview of the published literature appertaining to the use of TNP therapy in the management of acute wounds by an international panel of experts using standard methods of appraisal.

Approach to debridement in necrotizing fasciitis.

Aggressive debridement is a cornerstone intervention in necrotizing fasciitis. Our approach consists of 4 steps: (1) confirming the diagnosis and isolate the causative organism; (2) defining the extent of fasciitis; (3) surgical excision; and (4) post-excision wound care. The extent of the infection is defined by probing the wound bluntly.