Severe postpartum disruption of the pelvic ring: report of two cases and review of the literature

Pelvic dislocations are rare during labor, and the treatment is controversial. We report two cases of young women who sustained postpartum disruption of the pelvic ring: one case is an 8.8 cm wide separation of the pubic symphysis with sacroiliac joint disruption underwent surgical stabilization and the second case with 4.0 cm disruption being treated non-operatively. These cases illustrated of importance of accurate diagnosis, careful physical exam, fully informed consent and specific treatment for this condition

Induction of autophagy is a key component of all-trans-retinoic acid-induced differentiation in leukemia cells and a potential target for pharmacological modulation

Acute myeloid leukemia (AML) is characterized by the accumulation of immature blood cell precursors in the bone marrow. Pharmacologically overcoming the differentiation block in this condition is an attractive therapeutic avenue, which has achieved success only in a subtype of AML, acute promyelocytic leukemia (APL). Attempts to emulate this success in other AML subtypes have thus far been unsuccessful. Autophagy is a conserved protein degradation pathway with important roles in mammalian cell differentiation, particularly within the hematopoietic system. In the study described here, we investigated the functional importance of autophagy in APL cell differentiation. We found that autophagy is increased during all-trans-retinoic acid (ATRA)-induced granulocytic differentiation of the APL cell line NB4 and that this is associated with increased expression of LC3II and GATE-16 proteins involved in autophagosome formation. Autophagy inhibition, using either drugs (chloroquine/3-methyladenine) or short-hairpin RNA targeting the essential autophagy gene ATG7, attenuates myeloid differentiation. Importantly, we found that enhancing autophagy promotes ATRA-induced granulocytic differentiation of an ATRA-resistant derivative of the non-APL AML HL60 cell line (HL60-Diff-R). These data support the development of strategies to stimulate autophagy as a novel approach to promote differentiation in AML

Strategies to reduce medication errors with reference to older adults

Background  In Australia, around 59% of the general population uses prescription medication with this number increasing to about 86% in those aged 65 and over and 83% of the population over 85 using two or more medications simultaneously. A recent report suggests that between 2% and 3% of all hospital admissions in Australia may be medication related with older Australians at higher risk because of higher levels of medicine intake and increased likelihood of being admitted to hospital. The most common medication errors encountered in hospitals in Australia are prescription/medication ordering errors, dispensing, administration and medication recording errors. Contributing factors to these errors have largely not been reported in the hospital environment. In the community, inappropriate drugs, prescribing errors, administration errors, and inappropriate dose errors are most common. Objectives  To present the best available evidence for strategies to prevent or reduce the incidence of medication errors associated with the prescribing, dispensing and administration of medicines in the older persons in the acute, subacute and residential care settings, with specific attention to persons aged 65 years and over. Search strategy  Bibliographic databases PubMed, Embase, Current contents, The Cochrane Library and others were searched from 1986 to present along with existing health technology websites. The reference lists of included studies and reviews were searched for any additional literature. Selection criteria  Systematic reviews, randomised controlled trials and other research methods such as non-randomised controlled trials, longitudinal studies, cohort or case-control studies, or descriptive studies that evaluate strategies to identify and manage medication incidents. Those people who are involved in the prescribing, dispensing or administering of medication to the older persons (aged 65 years and older) in the acute, subacute or residential care settings were included. Where these studies were limited, evidence available on the general patient population was used. Data collection and analysis  Study design and quality were tabulated and relative risks, odds ratios, mean differences and associated 95% confidence intervals were calculated from individual comparative studies containing count data where possible. All other data were presented in a narrative summary. Results  Strategies that have some evidence for reducing medication incidents are: •  computerised physician ordering entry systems combined with clinical decision support systems; •  individual medication supply systems when compared with other dispensing systems such as ward stock approaches; •  use of clinical pharmacists in the inpatient setting; •  checking of medication orders by two nurses before dispensing medication; •  a Medication Administration Review and Safety committee; and •  providing bedside glucose monitors and educating nurses on importance of timely insulin administration. In general, the evidence for the effectiveness of intervention strategies to reduce the incidence of medication errors is weak and high-quality controlled trials are needed in all areas of medication prescription and delivery

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field