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Background Patient blood management (PBM) is especially applicable in major spine surgery, during which bleeding and transfusion are common. What remains unclear in this setting is the overall impact of bundled PBM measures on transfusion requirements and clinical outcomes. We compared these outcomes before and after implementing a PBM program. Study design and methods We conducted a retrospective review of 928 adult complex spine surgery patients performed by a single surgeon between January 2009 and June 2016. Although PBM measures were phased in over time, tranexamic acid (TXA) administration became standard protocol in July 2013, which defined our pre- and post-PBM periods. Transfusion rates for all blood components before and after PBM implementation were compared, as were morbid event rates and mortality. Results Baseline characteristics were similar before and after PBM. Before PBM, the mean number of units/patient decreased for red blood cells (RBCs; by 19.5%; p = 0.0057) and plasma (by 33%; p = 0.0008), but not for platelets (p = 0.15). After risk adjustment by multivariable analyses, the composite outcome of morbidity or mortality showed a nonsignificant trend toward improvement after PBM (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.39-1.01; p = 0.055), and the risk of thrombotic events was unchanged (OR, 1.12; 95% CI, 0.42-2.58; p = 0.80). Conclusion In complex spine surgery, a multifaceted PBM program that includes TXA can be advantageous by reducing transfusion requirements without changing clinical outcomes. more...

BACKGROUND Although females have a lower baseline hemoglobin (Hb) compared to males, it is unknown whether females have a greater tolerance for anemia when hospitalized. We tested the hypothesis that females tolerate severe anemia better than males, with decreased inpatient mortality in this setting. STUDY DESIGN AND METHODS We conducted a retrospective cohort study in 230,644 adult patients admitted to Johns Hopkins Hospital from January 2009 to June 2016. The relationships between nadir Hb and percentage change in Hb with inpatient mortality were assessed for nontransfused males and females. A multivariable logistic regression was used to determine risk-adjusted differences between males and females for the likelihood of inpatient mortality at nadir Hb levels of 5, 6, and 7 g/dL. RESULTS Males had increased mortality when nadir Hb was 6.0 g/dL or less (p < 0.05), whereas females did not. The risk-adjusted likelihood for inpatient mortality was greater for males compared to females at a nadir Hb of 6 g/dL or less (odds ratio, 1.84; 95% confidence interval, 1.09-3.16) (p = 0.02), but this sex-related difference was not significant at a nadir Hb of 5 or 7 g/dL or less. Inpatient mortality increased significantly in both males and females when the percentage decrease in Hb was greater than 50% from baseline (p < 0.05). CONCLUSIONS Compared to males, females tolerate a lower nadir Hb, but a similar percentage change in Hb, before an increase in inpatient mortality is recognized. The findings suggest that females may be "preconditioned" to tolerate anemia better than males. more...

BACKGROUND AND OBJECTIVES Platelet dosing has been studied in adult oncology inpatients, but there is almost no published evidence to guide platelet dosing for adult outpatients. We evaluated transfusion indices after 1 unit and 2 unit apheresis platelet transfusions at our hospital to determine whether a benefit to 2-unit transfusions could be detected. MATERIALS AND METHODS A retrospective chart review was conducted of all adult oncology patients who received an outpatient platelet transfusion over a 16-month period (July 2016-November 2017). Pre- and post-transfusion platelet count, and chronology of subsequent platelet transfusions were compared. RESULTS A total of 8467 platelet transfusions were administered to 602 patients during the study period. 59·8% of patients (n = 360) were transfused interchangeably with one or two platelets throughout the study period. The primary study population were comprised of these patients. On average, a 2-unit platelet transfusions resulted in a higher immediate post-transfusion platelet count (43 vs. 37 x 103 /μl, P more...

Rationale Microbial natural products are often biosynthesized as classes of structurally related compounds that have similar tandem mass spectrometry (MS/MS) fragmentation patterns. Mining MS/MS datasets for precursor ions that share diagnostic or common features enables entire chemical classes to be identified, including novel derivatives that have previously been unreported. Analytical data analysis tools that can facilitate a class-targeted approach to rapidly dereplicate known compounds and identify structural variants within complex matrices would be useful for the discovery of new natural products. Methods A diagnostic fragmentation filtering (DFF) module was developed for MZmine to enable the efficient screening of MS/MS datasets for class-specific product ions(s) and/or neutral loss(es). This approach was applied to series of the structurally related chaetoglobosin and cytochalasin classes of compounds. These were identified from the culture filtrates of three fungal genera: Chaetomium globosum, a putative new species of Penicillium (called here P. cf. discolor: closely related to P. discolor), and Xylaria sp. Extracts were subjected to LC/MS/MS analysis under positive electrospray ionization and operating in a data-dependent acquisition mode, performed using a Thermo Q-Exactive mass spectrometer. All MS/MS datasets were processed using the DFF module and screened for diagnostic product ions at m/z 130.0648 and 185.0704 for chaetoglobosins, and m/z 120.0808 and 146.0598 for cytochalasins. Results Extracts of C. globosum and P. cf. discolor strains revealed different mixtures of chaetoglobosins, whereas the Xylaria sp. produced only cytochalasins; none of the strains studied produced both classes of compounds. The dominant chaetoglobosins produced by both C. globosum and P. cf. discolor were chaetoglobosins A, C, and F. Tetrahydrochaetoglobosin A was identified from P. cf. discolor extracts and is reported here for the first time as a natural product. The major cytochalasins produced by the Xylaria sp. were cytochalasin D and epoxy cytochalasin D. A larger unknown "cytochalasin-like" molecule with the molecular formula C38 H47 NO10 was detected from Xylaria sp. culture filtrate extracts and is a current target for isolation and structural characterization. Conclusions DFF is an effective LC/MS data analysis approach for rapidly identifying entire classes of compounds from complex mixtures. DFF has proved useful in the identification of new natural products and allowing for their partial characterization without the need for isolation. more...

BACKGROUND Blood transfusion can be lifesaving for patients with hemorrhage; however, transfusion requirements for victims of gun violence are poorly understood. STUDY DESIGN AND METHODS In an urban, Level 1 trauma center, 23,422 trauma patients were analyzed in a retrospective cohort study. Patients with gunshot wounds (GSWs) (n = 2,672; 11.4% of trauma patients) were compared to those with non-GSW traumatic injuries from 2005 to 2017, to assess blood utilization. RESULTS The GSW cohort was approximately five times more likely to require transfusion (538 of 2672 [20.1%] vs. 798 of 20,750 [3.9%]; p < 0.0001), and the number of blood component units transfused per patient was approximately 10 times greater (3.3 ± 13.5 vs. 0.31 ± 3.8 units/patient; p < 0.0001), compared to the non-GSW cohort. The risk-adjusted likelihood of requiring high-dose transfusion was greater in the GSW cohort (odds ratio, 2.38; 95% confidence interval, 1.14-5.80), and requirements were increased for all four blood components (red blood cells, platelets, plasma, and cryoprecipitate). Patients with GSWs had approximately 14 times greater overall mortality (653 of 2672 [24.4%] vs. 352 of 20,750 [1.7%]; p < 0.0001]. Compared to non-GSW penetrating injuries (e.g., stab wounds), those with GSWs had approximately four times higher transfusion requirements (3.3 ± 13.5 vs. 0.80 ± 3.8 units/patient; p < 0.0001), and approximately eight times greater overall mortality (653 of 2672 [24.4%] vs. 28 of 956 [2.9%]; p < 0.0001). CONCLUSIONS Compared to other traumatic injuries, GSW injuries are associated with substantially greater blood utilization and mortality. Trauma centers treating GSW injuries should have ready access to all blood components and ability to implement massive transfusions. more...

Informal urban settlements determine the well-being of a large section of global humanity. Yet there has been little research on their role in facilitating social mobility. In theory such settlements may foster human progress by linking rural-urban migrants to the services, contacts and livelihoods concentrated in cities. The article uses longitudinal data for South Africa to explore the magnitude of social progression among people living within informal settlements compared with rural areas and formal urban areas. It finds that there may be some advantage from living in an informal settlement compared with a rural area, but the effect is not strong. The impact may be larger in the more prosperous Gauteng city-region than in other urban regions. This article is protected by copyright. All rights reserved. more...

Ascospores of Neosartorya, Byssochlamys and Talaromyces can be regarded as the most stress-resistant eukaryotic cells. They can survive exposure at temperatures as high as 85°C for 100 min or more. Neosartorya fischeri ascospores are more viscous and more resistant to the combined stress of heat and desiccation than the ascospores of Talaromyces macrosporus which contain predominantly trehalose. These ascospores contain trehalose-based oligosaccharides (TOS) that are novel compatible solutes, which are accumulated to high levels. These compounds are also found in other members of the genus Neosartorya and in some other genera within the order Eurotiales that also include Byssochlamys and Talaromyces. The presence of oligosaccharides was observed in species that had a relatively high growth temperature. TOS glasses have a higher glass transition temperature (Tg ) than trehalose, and they form a stable glass with crystallizing molecules, such as mannitol. Our data indicate that TOS are important for prolonged stabilization of cells against stress. The possible unique role of these solutes in protection against dry heat conditions is discussed. more...

Microtubules are important targets when studying potential anticancer agents since disturbance of these microtubule dynamics results in cell cycle arrest and cell death. 2-Methoxyestradiol is a naturally occurring metabolite that exerts antiproliferative activity and induces apoptosis. Due to limited biological accessibly and rapid metabolic degradation, several analogs were synthesized. This study investigated the antiproliferative influence of an 2-methoxyestradiol analog, (8R, 13S, 14S, 17S)-2-Ethyl-13-methyl-7, 8, 9, 11, 12,13, 14, 15, 16, 17-decahydro-6H-cyclopenta[a]phenanthrane-3, 17-diyl bis(sulfamate) (EMBS) on cell proliferation, morphology and apoptosis induction in a estrogen receptor-positive breast adenocarcinoma cells line (MCF-7), estrogen receptor-negative highly metastatic breast cell line (MDA-MB-231) and a non-tumorigenic breast epithelial cell line (MCF-12A). Spectrophotometry results indicated that EMBS exerted differential antiproliferative activity in the three cell lines. Cell growth of the breast adenocarcinoma and highly metastatic breast cell line reached a plateau effect at 0.4 μM after 24 h of exposure. Light microscopy and polarization-optical transmitted light differential interference contrast demonstrated compromised cell density, cells blocked in metaphase and the presence of apoptotic characteristics after EMBS exposure for 24 h in all three cell lines. Transmission electron microscopy and scanning electron microscopy revealed hallmarks of apoptosis namely the presence of apoptotic bodies, shrunken cells and cell debris in EMBS-exposed cells. This investigation demonstrated that EMBS does exert antimitotic activity and induces apoptosis contributing to elucidating the signal transduction of EMBS in tumorigenic and non-tumorigenic breast cell lines. Findings warrant in-depth analysis of specific targets in vitro and subsequent in vivo investigation for anticancer therapy. more...

Thrombotic thrombocytopenic purpura (TTP) has been associated with human immunodeficiency virus (HIV) infection. With the high prevalence of HIV in sub-Saharan Africa, HIV-associated TTP is the most common form of this disease seen in the South African population. Several case reports describe myocardial infarction in HIV-negative TTP patients. The case of the first HIV-positive patient who presented with clinical signs and symptoms of TTP and myocardial injury is reported in this study. A patient with fragmentation haemolysis and thrombocytopenia presented with angina. Risk factors for ischaemic heart disease were absent. An electrocardiogram (EKG) revealed ST-segment elevation and a significantly raised Troponin T level. The patient's HIV test was positive and a diagnosis of myocardial injury with HIV-associated TTP was made. The patient was treated with plasma infusion and steroid therapy. Due to poor response, the therapy was changed to plasma exchange. The patient recovered fully and subsequent coronary angiography revealed normal coronary vessels. Treatment of myocardial infarction in TTP is controversial, but the treatment cornerstone should remain plasma infusion or plasma exchange. As patients are often young and do not have the classical risk factors of ischaemic heart disease, a high level of suspicion and routine exclusion of myocardial ischaemia in these patients are advised. more...

The Medical Research Council of South Africa (AK076; AL343), the Cancer Association of South Africa (AK246), RESCOM, School of Medicine (Faculty of Health Sciences, University of Pretoria), the National Research Foundation of South Africa (AL239) and the Struwig-Germeshuysen Cancer Research Trust of South Africa (AN074). The Bioinformatics and Computational Biology Unit (University of Pretoria) contributed to the in silico-design of the compound. more...

Scanning electron microscopy and histological techniques were used to study the structure and possible function of the frontal pit present in the frons of Lipoptena annalizeae. In the adult fly the opening leads into a closed sclerotized tube (torma) within a sclerite (fulcrum), to which the cibarial pump muscles are attached enabling the retraction of the proboscis. A method for softening the heads of Lipoptena for histological studies is also described. © 1994 Wiley-Liss, Inc. more...