These studies have examined the effect of hypoxia inducible factor 1α (HIF-1α) on nucleotide metabolism in the ischemic heart using a genetic mouse model with heart-specific and regulated expression of a stable form of HIF-1α. We find that AMP deaminase (AMPD), the entry point of the purine nucleotide cycle (PNC), is induced by HIF-1α at the level of mRNA, protein, and activity. AMP that accumulates during ischemia can be metabolized to adenosine by 5'-nucleotidase or to IMP by AMPD. Consistent with the finding of AMPD induction, adenosine accumulation during ischemia was much attenuated in HIF-1α-expressing hearts. Further investigation of nucleotide salvage enzymes found that hypoxanthine phosphoribosyl transferase (HPRT) is also upregulated in HIF-1α-expressing hearts. Treatment of hearts with an inhibitor of the PNC, hadacidin, hastens the fall of the adenylate energy charge during ischemia and the accumulation of AMP. The results provide new insight into the role of the PNC in the heart, especially as it relates to ischemia, and indicate that HIF-1α regulates nucleotide metabolism as a compensatory response to hypoxia.

What is known and objective: Treatment of methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia is a long-standing challenge to health care, often complicated by metastatic infections, treatment failure and mortality. When MRSA bacteraemia persists despite adequate initial treatment, current Infectious Diseases Society of America guidelines recommend evaluation and removal of possible sources of infection. In addition, a change in therapy may be considered. The objective of this review was to explore the therapeutic options for the treatment of persistent MRSA bacteraemia. Methods: A literature search of PubMed, MEDLINE and Google Scholar was performed using the following search terms: [methicillin-resistant Staphylococcus aureus OR MRSA] AND [bacteraemia OR bloodstream infection] AND [persistent OR persistence OR refractory OR treatment failure OR salvage] AND treatment. We evaluated relevant, adult, English-language, peer-reviewed studies published between 1985 and May 2018. In vitro and animal studies were considered as supportive of in vivo data. Results and discussion: Randomized, controlled trials are lacking. However, case series and case reports support multiple treatment options including high-dose daptomycin in combination with an antistaphylococcal β-lactam, ceftaroline, trimethoprim-sulfamethoxazole (TMP-SMX) or fosfomycin; ceftaroline alone or in combination with vancomycin or TMP-SMX; linezolid alone or in combination with a carbapenem, or telavancin. What is new and conclusion: Given the heterogeneity of the data, a preferred regimen has not emerged. Prescribers must take into consideration recent exposure, source control, and available synergy and clinical data. Further comparative trials are needed to establish a preferred regimen and the creation of a universal treatment algorithm.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18163号 / 医博第3883号 / 新制||医||1003(附属図書館) / 31021 / 京都大学大学院医学研究科医学専攻 / (主査)教授 福山 秀直, 教授 富樫 かおり, 教授 増永 慎一郎 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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Introduction: Below knee amputation is the safest treatment for aggressive benign and malignant bone tumours of the distal tibia yielding good oncological and functional results. However, in selected patients where limb salvage is feasible and amputation unacceptable to the patient, limb salvage using a distal tibial replacement (DTR) can be considered. This study aims to present the oncological and functional results of the use of this treatment method in our unit. Patients & Methods: A retrospective folder review was performed for all 10 patients who received a modular distal tibial replacement between 01/01/2005 and 31/01/2019 for a primary bone tumour either benign aggressive or malignant. Six were female and the mean age was 31 (1275) years. There were five patients with giant cell tumour of bone, four with osteosarcoma and one with a low-grade chondrosarcoma. The patients with osteosarcoma had neo-adjuvant chemotherapy before surgery. Function was assessed by the Musculoskeletal Tumor Society (MSTS) score. Results: There were six females and four males, with a mean age of 31 (12-75) years. Two patients had local recurrence treated with a BKA and one other patient died of metastases three years postoperatively. At a mean follow-up of three years, the remaining eight patients had a mean MSTS score of 83% (67–93%). There were no radiological signs of loosening, and no revision surgeries. Conclusion: Endoprosthetic replacement of the distal tibia for primary bone tumours can be a safe treatment option in very selected cases.

BACKGROUND: Evidence supporting beta-lactam plus vancomycin synergy for methicillin-resistant (MRSA) continues to grow. Current evidence demonstrates that combination therapy is associated with shorter time to blood sterilization than vancomycin monotherapy. However, this combination has not been reported as salvage therapy for persistent MRSA bacteremia. CASE REPORT: We report a case of an 81-year-old male who was successfully treated with vancomycin plus nafcillin after failing vancomycin monotherapy, daptomycin monotherapy, and daptomycin plus gentamicin combination therapy. The patient originally presented with sepsis from a suspected urinary tract infection. Blood cultures drawn on days 1, 3, 5, 15, 19, 23, and 28 remained positive for MRSA despite multiple antimicrobial therapy changes. On day 29, therapy was changed to vancomycin plus nafcillin. Blood cultures drawn on day 32 remained negative. After 11 days, nafcillin was changed to piperacillin-tazobactam due to an infected decubitus ulcer. The combination was continued for 42 days after achieving blood sterility, 71 days after the patient originally presented. Evidence regarding salvage therapy for persistent bacteremia is sparse and is limited to case reports and case series. CONCLUSION: This case report supports that vancomycin plus an anti-staphylococcal beta-lactam combination should be further studied as salvage therapy for persistent MRSA bacteremia.

Recycling has often been overlooked in the conversation on how to combat climate change. The reasons behind recycling being pushed to the wayside point to difficulties in mobilizing the general public, the inherent design of recyclables, and confusing legislation. However, throughout history there have been notable “salvage” (recycling) processes that changed social fabrics and economic structures. This thesis compares the past salvaging revolution of Great Britain during World War II with the current recycling revolution of Sweden. The thesis uses theories of mobilization in order to contrast wartime events with contemporary peaceful democracy. Through the theories of wartime mobilization, discursive mobilization and material ecological mobilization, the thesis creates a content analysis based on the author’s own 5-point scale system, in combination with semi-structured interviews with key actors in the Swedish recycling sector and historical anecdotes from World War II. The findings of the thesis show that there is a gap in quality of mobilization done in past British salvaging efforts and present Swedish recycling efforts, which involves the extent of active state engagement, commitment to the promotion of recycling, and the under/well-establishment of end user systems.

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Waste from construction and demolition-building activities is increasing every day. Landfills have almost reached their capacity. When thinking about the negative impact of demolishing activities on the environment it becomes very necessary to think about reusing and recycling building materials in new construction or perhaps better recycling our thoughts on how to make use of waste materials. In Kevin Lynch's book, Wasting Away, he wrote: "Architects must begin to think about holes in the ground and about flows of materials." Studies show that construction and demolition activities are the primary source of solid waste worldwide. For example construction and demolition wastes constitute about 40% of the total solid waste stream in the United States. The growing interest in materials and resource conservation in the United States is inherent in the growth of green building practices. The USGBC identifies six categories in the Materials and Resources (MR) section of LEED. One of these six categories is Resource Reuse (RR). Interestingly enough, a recent study about the cost of green buildings indicated that RR was the category credits least often achieved in most LEED certified projects. Literature suggests that there are a number of constraints and barriers to resource reuse primarily due to the complexity of buildings but perhaps the most important barrier, according to many architects, is the lack of easily accessible information to the design team on resource reuse. Therefore, as we promote the idea of building material reuse to a wider audience of designers and architects, we mus not forget that in the Architecture, Engineering and Construction (AEC) industry, both Reuse and Recycle terms are used interchangeably without yet a clear distinction between them. The use of arbitrary descriptions to distinguish reuse from recycle has caused nothing but more confusion to the public. This study argues that the real distinction between reuse and recycle exists in Knowledge and Information. This suggests that design with reuse requires a paradigm shift in the required knowledgebase and the way information flows within the design process. Unfortunately, the structure of this paradigm shift is not known and has not been well defined. Since knowledge forms the core of building a Decision Support Systems (DSS) for a design team in order to consider reuse, it is necessary to capture the required knowledge and information from the industry experts through a Knowledge Acquisition (KA) process. This knowledge can then be used to 1) identify the building material reuse criteria and 2) to build a prescriptive decision model and 3) to map the process design of the current traditional architectural design workflow and the proposed one. The overarching goal of this study is to use the building material reuse knowledgebase for 1) building a Unified Virtual Repository database to be connected to all available physical repositories and share a unified standard of information. 2) When the unified virtual repository is integrated with the Building Information Modeling (BIM) database, the DSS can work as a feedback and feed forward support for architects and designers as they consider building material reuse in new designs and constructions. / Ph. D.