Efficacy and safety of misoprostol compared to methotrexate plus misoprostol for the medical management of abortion in Bogotá, Colombia. A randomized clinical trial

Evaluar la eficacia y seguridad del misoprostol frente al metotrexato más misoprostol para el manejo médico de pacientes con aborto retenido o embarazo anembrionado. Se realizó un estudio clínico aleatorizado en el que se incluyeron pacientes con embarazo anembrionado o aborto retenido de hasta 63 días y diagnosticado por ecografía. Estas fueron aleatorizadas a metotrexato 50 mg intramuscular más misoprostol 800 mcg intravaginal (grupo 1) u 800 mcg de misoprostol intravaginal (grupo 2). A continuación se evaluó la tasa de aborto completo, incluyendo las pacientes que requirieron un segundo ciclo de rescate con sus respectivas complicaciones. Un total de 52 pacientes fueron aleatorizadas al grupo de terapia combinada y 66 al grupo de monoterapia. 92% de las pacientes en el grupo de misoprostol más metotrexato presentaron aborto completo por ecografía frente a 86% de las pacientes en el grupo de misoprostol (p=0,24). Por otro lado, dos de las pacientes del grupo de terapia combinada (6%) requirieron dosis de rescate en comparación con cinco en el grupo de misoprostol (11%), (p=0,348). De igual modo, tres pacientes requirieron legrado uterino obstétrico en el grupo de terapia combinada frente a cinco pacientes en el grupo de monoterapia con misoprostol (p=0,69). En definitiva, los dos esquemas resultaron seguros para las pacientes. Los resultados permitieron concluir que, en el manejo médico del aborto retenido o embarazo anembrionado menor a 63 días, la monoterapia con una dosis de 800 mcg de misoprostol intravaginal no mostró diferencias significativas en comparación con un esquema de terapia combinada con metotrexato y misoprostol.Evaluating the efficacy and safety of misoprostol compared to methotrexate plus misoprostol for the medical management of patients suffering from retained abortion/anembryonic pregnancy. This was a randomized clinical experiment. Patients having a gestational age of less than 63 days who were suffering anembryonic pregnancy/retained abortion as diagnosed by ecography were included. They were randomized into 2 groups receiving 50 mg intra muscular methotrexate plus 800 mcg intravaginal misoprostol (group 1) or 800 mcg intravaginal misoprostol (group 2). The complete abortion rate was evaluated, including patients who required a rescue dose with their respective complications. Results: a total of 52 patients were randomized to the combined therapy group and 66 to the monotherapy group; 92% presented complete abortion by ecography in the misoprostol plus methotrexate group and 86% in the misoprostol group (p=0.24). Two of the patients from the combined therapy group (6%) required a rescue dose compared to five in the misoprostol group (11%) (p=0.348). Three patients required obstetric uterine dilation and curettage (D&C) (in the combined therapy group whilst five needed it in the monotherapy with misoprostol group (p=0.69). Both schemes proved safe for the patients. The profile for medical management of females having a gestational age of less than 63 days who were diagnosed as having retained abortion or anembryonic pregnancy receiving intravaginal 800 mcg de misoprostol monodosis did not show significant differences when compared to a combined methotrexate and misoprostol therapy scheme

Excavation at Aguas Buenas, Robinson Crusoe Island, Chile, of a gunpowder magazine and the supposed campsite of Alexander Selkirk, together with an account of early navigational dividers

Excavations were undertaken of a ruined building at Aguas Buenas, identified as an 18th-century Spanish gunpowder magazine. Evidence was also found for the campsite of an early European occupant of the island. A case is made that this was Alexander Selkirk, a castaway here from 1704 to 1709. Selkirk was the model for Defoe’s Robinson Crusoe. A detailed discussion is given of a fragment of copper alloy identifi ed as being from a pair of navigational dividers

Travel routes to remote ocean targets reveal the map sense resolution for a marine migrant

How animals navigate across the ocean to isolated targets remains perplexing greater than 150 years since this question was considered by Charles Darwin. To help solve this long-standing enigma, we considered the likely resolution of any map sense used in migration, based on the navigational performance across different scales (tens to thousands of kilometres). We assessed navigational performance using a unique high-resolution Fastloc-GPS tracking dataset for post-breeding hawksbill turtles (Eretmochelys imbricata) migrating relatively short distances to remote, isolated targets on submerged banks in the Indian Ocean. Individuals often followed circuitous paths (mean straightness index = 0.54, range 0.14-0.93, s.d. = 0.23, n = 22), when migrating short distances (mean beeline distance to target = 106 km, range 68.7-178.2 km). For example, one turtle travelled 1306.2 km when the beeline distance to the target was only 176.4 km. When off the beeline to their target, turtles sometimes corrected their course both in the open ocean and when encountering shallow water. Our results provide compelling evidence that hawksbill turtles only have a relatively crude map sense in the open ocean. The existence of widespread foraging and breeding areas on isolated oceanic sites points to target searching in the final stages of migration being common in sea turtles

Estimating the cost-effectiveness of detecting cases of chronic hepatitis C infection on reception into prison

Background In England and Wales where less than 1% of the population are Injecting drug users (IDUs), 97% of HCV reports are attributed to injecting drug use. As over 60% of the IDU population will have been imprisoned by the age of 30 years, prison may provide a good location in which to offer HCV screening and treatment. The aim of this work is to examine the cost effectiveness of a number of alternative HCV case-finding strategies on prison reception Methods A decision analysis model embedded in a model of the flow of IDUs through prison was used to estimate the cost effectiveness of a number of alternative case-finding strategies. The model estimates the average cost of identifying a new case of HCV from the perspective of the health care provider and how these estimates may evolve over time. Results The results suggest that administering verbal screening for a past positive HCV test and for ever having engaged in illicit drug use prior to the administering of ELISA and PCR tests can have a significant impact on the cost effectiveness of HCV case-finding strategies on prison reception; the discounted cost in 2017 being £2,102 per new HCV case detected compared to £3,107 when no verbal screening is employed. Conclusion The work here demonstrates the importance of targeting those individuals that have ever engaged in illicit drug use for HCV testing in prisons, these individuals can then be targeted for future intervention measures such as treatment or monitored to prevent future transmission

Perspectives of TB survivors and policymakers on post-TB disability

Background: An international multistakeholder participatory workshop was hosted in the Gambia, West Africa, in November 2021. Objectives: To explore the experiences, challenges and recommendations of workshop participants on health and wellbeing after TB treatment. Methods: An exploratory, descriptive, qualitative approach was used for data collection through facilitator-guided group discussions. Workshop participants included adolescent and adult TB survivors, and representatives of TB advocacy groups and the policy sector. Discussions were audio-recorded and transcribed verbatim, and the data were analysed using a deductive thematic approach. Results: Overall, 38 participants (22 women) from six West African countries participated in the workshop, comprising 33 TB survivors and advocacy group representatives and 5 participants from the policy sector. Although some TB survivors noted improved ability to carry out physical activities, others continued to experience detrimental effects on their family life, social interactions, physical health and ongoing stigma. Policymakers emphasised the lack of data and clear guidelines on post-TB disability. Conclusions: Some TB survivors continue to suffer detrimental effects of the illness even after treatment completion. However, available data on post-TB disability is inadequate to support policy adoption. Therefore, there is an urgent need for increased advocacy, awareness and research to bridge knowledge gaps

Understanding age-related modifications of motor control strategies

ISSN:1743-000

Introducing a new breed of wine yeast: interspecific hybridisation between a commercial Saccharomyces cerevisiae wine yeast and Saccharomyces mikatae

Interspecific hybrids are commonplace in agriculture and horticulture; bread wheat and grapefruit are but two examples. The benefits derived from interspecific hybridisation include the potential of generating advantageous transgressive phenotypes. This paper describes the generation of a new breed of wine yeast by interspecific hybridisation between a commercial Saccharomyces cerevisiae wine yeast strain and Saccharomyces mikatae, a species hitherto not associated with industrial fermentation environs. While commercially available wine yeast strains provide consistent and reliable fermentations, wines produced using single inocula are thought to lack the sensory complexity and rounded palate structure obtained from spontaneous fermentations. In contrast, interspecific yeast hybrids have the potential to deliver increased complexity to wine sensory properties and alternative wine styles through the formation of novel, and wider ranging, yeast volatile fermentation metabolite profiles, whilst maintaining the robustness of the wine yeast parent. Screening of newly generated hybrids from a cross between a S. cerevisiae wine yeast and S. mikatae (closely-related but ecologically distant members of the Saccharomyces sensu stricto clade), has identified progeny with robust fermentation properties and winemaking potential. Chemical analysis showed that, relative to the S. cerevisiae wine yeast parent, hybrids produced wines with different concentrations of volatile metabolites that are known to contribute to wine flavour and aroma, including flavour compounds associated with non-Saccharomyces species. The new S. cerevisiae x S. mikatae hybrids have the potential to produce complex wines akin to products of spontaneous fermentation while giving winemakers the safeguard of an inoculated ferment.Jennifer R. Bellon, Frank Schmid, Dimitra L. Capone, Barbara L. Dunn, Paul J. Chamber

Redox-Mediated Inactivation of the Transcriptional Repressor RcrR is Responsible for Uropathogenic Escherichia coli's Increased Resistance to Reactive Chlorine Species

The ability to overcome stressful environments is critical for pathogen survival in the host. One challenge for bacteria is the exposure to reactive chlorine species (RCS), which are generated by innate immune cells as a critical part of the oxidative burst. Hypochlorous acid (HOCl) is the most potent antimicrobial RCS and is associated with extensive macromolecular damage in the phagocytized pathogen. However, bacteria have evolved defense strategies to alleviate the effects of HOCl-mediated damage. Among these are RCS-sensing transcriptional regulators that control the expression of HOCl-protective genes under non-stress and HOCl stress. Uropathogenic Escherichia coli (UPEC), the major causative agent of urinary tract infections (UTIs), is particularly exposed to infiltrating neutrophils during pathogenesis; however, their responses to and defenses from HOCl are still completely unexplored. Here, we present evidence that UPEC strains tolerate higher levels of HOCl and are better protected from neutrophil-mediated killing compared with other E. coli. Transcriptomic analysis of HOCl-stressed UPEC revealed the upregulation of an operon consisting of three genes, one of which encodes the transcriptional regulator RcrR. We identified RcrR as a HOCl-responsive transcriptional repressor, which, under non-stress conditions, is bound to the operator and represses the expression of its target genes. During HOCl exposure, however, the repressor forms reversible intermolecular disulfide bonds and dissociates from the DNA resulting in the derepression of the operon. Deletion of one of the target genes renders UPEC significantly more susceptible to HOCl and phagocytosis indicating that the HOCl-mediated induction of the regulon plays a major role for UPEC’s HOCl resistance

Annelid functional genomics reveal the origins of bilaterian life cycles.

Indirect development with an intermediate larva exists in all major animal lineages1, which makes larvae central to most scenarios of animal evolution2-11. Yet how larvae evolved remains disputed. Here we show that temporal shifts (that is, heterochronies) in trunk formation underpin the diversification of larvae and bilaterian life cycles. We performed chromosome-scale genome sequencing in the annelid Owenia fusiformis with transcriptomic and epigenomic profiling during the life cycles of this and two other annelids. We found that trunk development is deferred to pre-metamorphic stages in the feeding larva of O. fusiformis but starts after gastrulation in the non-feeding larva with gradual metamorphosis of Capitella teleta and the direct developing embryo of Dimorphilus gyrociliatus. Accordingly, the embryos of O. fusiformis develop first into an enlarged anterior domain that forms larval tissues and the adult head12. Notably, this also occurs in the so-called 'head larvae' of other bilaterians13-17, with which the O. fusiformis larva shows extensive transcriptomic similarities. Together, our findings suggest that the temporal decoupling of head and trunk formation, as maximally observed in head larvae, facilitated larval evolution in Bilateria. This diverges from prevailing scenarios that propose either co-option9,10 or innovation11 of gene regulatory programmes to explain larva and adult origins