Fatal breakthrough mucormycosis in a multivisceral transplant patient receiving micafungin: Case report and literature review.

INTRODUCTION: Antifungal agents are routinely used in the post-transplant setting for both prophylaxis and treatment of presumed and proven fungal infections. Micafungin is an echinocandin-class antifungal with broad antifungal cover and favorable side effect profile but, notably, it has no activity against molds of the order Mucorales. PRESENTATION OF CASE: A 47-year-old woman underwent multivisceral transplantation for intestinal failure-associated liver disease. She had a prolonged post-operative recovery complicated by invasive candidiasis and developed an intolerance to liposomal amphotericin B. In view of her immunosuppression, she was commenced on micafungin as prophylaxis to prevent invasive fungal infection. However, she developed acute graft versus host disease with bone marrow failure complicated by disseminated mucormycosis which was only diagnosed post mortem. DISCUSSION: Non-Aspergillus breakthrough mold infections with micafungin therapy are rare with only eight other cases having been described in the literature. Breakthrough infections have occurred within one week of starting micafungin. Diagnosis is problematic and requires a high degree of clinical suspicion and microscopic/histological examination of an involved site. The management of these aggressive infections involves extensive debridement and appropriate antifungal cover. CONCLUSION: A high level of suspicion of invasive fungal infection is required at all times in immunosuppressed patients, even those receiving antifungal prophylaxis. Early biopsy is required. Even with early recognition and aggressive treatment of these infections, prognosis is poor

Reductions in mesophyll and guard cell photosynthesis impact on the control of stomatal responses to light and CO2

Transgenic antisense tobacco plants with a range of reductions in sedoheptulose-1,7-bisphosphatase (SBPase) activity were used to investigate the role of photosynthesis in stomatal opening responses. High resolution chlorophyll a fluorescence imaging showed that the quantum efficiency of photosystem II electron transport (Fq′/Fm′) was decreased similarly in both guard and mesophyll cells of the SBPase antisense plants compared to the wild-type plants. This demonstrated for the first time that photosynthetic operating efficiency in the guard cells responds to changes in the regeneration capacity of the Calvin cycle. The rate of stomatal opening in response to a 30 min, 10-fold step increase in red photon flux density in the leaves from the SBPase antisense plants was significantly greater than wild-type plants. Final stomatal conductance under red and mixed blue/red irradiance was greater in the antisense plants than in the wild-type control plants despite lower CO2 assimilation rates and higher internal CO2 concentrations. Increasing CO2 concentration resulted in a similar stomatal closing response in wild-type and antisense plants when measured in red light. However, in the antisense plants with small reductions in SBPase activity greater stomatal conductances were observed at all Ci levels. Together, these data suggest that the primary light-induced opening or CO2-dependent closing response of stomata is not dependent upon guard or mesophyll cell photosynthetic capacity, but that photosynthetic electron transport, or its end-products, regulate the control of stomatal responses to light and CO2. © 2008 The Author(s)

“They aren’t all like that”: perceptions of clinical services, as told by self-harm online communities

Self-harm is a critical public health issue, with strikingly low rates of attendance to clinical services. By offering support, anonymity, and open discussions, online communities hold useful insights into the factors which influence help-seeking behavior. We explore the perceptions of clinical services in three self-harm online communities to understand which services are being used and why. Message threads from each community were extracted randomly until saturation, providing 513 messages across 60 threads. A thematic analysis was performed resulting in four key themes: access to appropriate services during an episode of self-harm, service preference, fears surrounding disclosure, and support

Host hindrance to HIV-1 replication in monocytes and macrophages

Monocytes and macrophages are targets of HIV-1 infection and play critical roles in multiple aspects of viral pathogenesis. HIV-1 can replicate in blood monocytes, although only a minor proportion of circulating monocytes harbor viral DNA. Resident macrophages in tissues can be infected and function as viral reservoirs. However, their susceptibility to infection, and their capacity to actively replicate the virus, varies greatly depending on the tissue localization and cytokine environment. The susceptibility of monocytes to HIV-1 infection in vitro depends on their differentiation status. Monocytes are refractory to infection and become permissive upon differentiation into macrophages. In addition, the capacity of monocyte-derived macrophages to sustain viral replication varies between individuals. Host determinants regulate HIV-1 replication in monocytes and macrophages, limiting several steps of the viral life-cycle, from viral entry to virus release. Some host factors responsible for HIV-1 restriction are shared with T lymphocytes, but several anti-viral mechanisms are specific to either monocytes or macrophages. Whilst a number of these mechanisms have been identified in monocytes or in monocyte-derived macrophages in vitro, some of them have also been implicated in the regulation of HIV-1 infection in vivo, in particular in the brain and the lung where macrophages are the main cell type infected by HIV-1. This review focuses on cellular factors that have been reported to interfere with HIV-1 infection in monocytes and macrophages, and examines the evidences supporting their role in vivo, highlighting unique aspects of HIV-1 restriction in these two cell types

Effects of Tensioning Errors in Split Transfers of Tibialis Anterior and Posterior Tendons

Background: Split transfers of the tibialis anterior and posterior tendons are commonly performed to address hindfoot varus deformities in patients with cerebral palsy, stroke, or brain injury. Poor outcomes from these procedures are often attributed to a failure to tension the transferred tendon properly, but the mechanical effects of this aspect of the procedure have not been quantified, to our knowledge. The purpose of the present study was to use a cadaver model to examine changes in the actions of these muscles that occur when the tensions in the halves of the split tendon are intentionally balanced or unbalanced to varying degrees. Methods: Tendon excursion was measured in seven cadaveric specimens before and after split tendon transfer with experimentally controlled tensions in the halves of the split tendon. The muscle moment arm, a quantitative indicator of the action of a muscle about a joint axis, was calculated as the derivative of tendon excursion with respect to the subtalar joint angle. Results: The tibialis anterior had an eversion moment arm with the subtalar joint in a neutral position following surgery, but the tibialis posterior had virtually no action in the neutral position. Following the split transfers with ideally balanced tension, subtalar joint rotations of \u3e5° strongly influenced the moment arm of the tibialis posterior (p \u3c 0.0002), indicating that its action depends on the position of the hindfoot. The moment arm of the tibialis anterior, however, was influenced only by rotations of ≥20° (p \u3e 0.1741 for each angle pair comparison of Conclusions: These results suggest that it is possible for a split tendon transfer to be successful over a large range of tensionings. Split transfer of the tibialis posterior tendon produced the desired mechanical outcome in that the tibialis posterior had an eversion moment arm when the foot was inverted and an inversion moment arm when the foot was everted. Split transfer of the tibialis anterior to the cuboid, however, produced a muscle that consistently functioned as an everter regardless of the position of the hindfoot. Clinical Relevance: Residual varus and overcorrection following a split tendon transfer are often attributed to technical errors in balancing the tension between the medial and lateral tendon halves. The findings of the present study, however, suggest that such surgical failures are likely caused by only the largest of imbalances in tendon tension