Severe Gastrointestinal Hemorrhage due to Monkeypox Virus-Associated Proctocolitis.

Monkeypox is primarily a painful cutaneous disease with occasional systemic manifestations. Monkeypox is transmitted predominantly through close physical contact and occasionally sexual contact. The first case was reported in the United States on May 17, 2022, in a recent monkeypox worldwide outbreak. We present a case of severe gastrointestinal bleeding as an atypical manifestation of monkeypox infection in a 40-year-old male with HIV. In our case, monkeypox-induced proctocolitis progressed to severe rectal bleeding requiring one unit of packed red blood cells transfusion despite one week of tecovirimat (TPOXX) therapy. So, patients should be educated about the possibility of unusual complications of monkeypox infection, i.e., bleeding in immunocompromised hosts.

A new set of microsatellite markers for Phoxinus lumaireul senso lato, Phoxinus marsilii and Phoxinus krkae for population and molecular taxonomic studies.

Minnows of the genus Phoxinus are common and an often highly abundant fish species in Palearctic freshwater habitats. Phoxinus species have a complex evolutionary history, phylogenetic relationships are not well understood and there are a number of unresolved taxonomic problems. There are currently 23 different mitochondrial genetic lineages identified in the genus Phoxinus, 13 of which are recognized as valid species. The taxonomic status of these lineages requires resolution, including the degree to which they can interbreed. Suitable nuclear molecular markers for studies of population divergence and interbreeding between morphotypes and mitochondrial lineages are lacking for Phoxinus species. Therefore, the authors developed a set of microsatellite markers using genomic information from Phoxinus lumaireul and tested their suitability for this and two related species, Phoxinus krkae and Phoxinus marsilii. Out of 16 microsatellite candidate loci isolated, 12 were found to be in Hardy-Weinberg equilibrium when tested on two P. lumaireul senso lato populations. Seven loci amplified across the three species, enabling the study of intraspecific genetic diversity and population structure within P. marsilii and P. krkae. The markers were able to clearly resolve differences among the three tested species, including the recently described P. krkae, and are therefore suitable for the detection of introgression and hybridization among populations consisting of mixtures of two or more of P. lumaireul s. l., P. marsilii and P. krkae.

Characterisation of the complete mitochondrial genome and 13 microsatellite loci through next-generation sequencing for the New Caledonian spider-ant Leptomyrmex pallens.

The complete mitochondrial genome and a set of polymorphic microsatellite markers were identified by 454 pyrosequencing (1/16th of a plate) for the New Caledonian rainforest spider-ant Leptomyrmex pallens. De novo genome assembly recovered the entire mitochondrial genome with mean coverage of 8.9-fold (range 1-27). The mitogenome consists of 15,591 base pairs including 13 protein-coding genes, 2 ribosomal subunit genes, 22 transfer RNAs, and a non-coding AT-rich region. The genome arrangement is typical of insect taxa and very similar to the only other published ant mitogenome from the Solenopsis genus, with the main differences consisting of translocations and inversions of tRNAs. A total of 13 polymorphic loci were also characterized using 41 individuals from a single population in the Aoupinié region, corresponding to workers from 21 nests and 16 foraging workers. We observed moderate genetic variation across most loci (mean number of alleles per locus = 4.50; mean expected heterozygosity = 0.53) with evidence of only two loci deviating significantly from Hardy-Weinberg equilibrium due to null alleles. Marker independence was confirmed with tests for linkage disequilibrium. Most loci cross amplified for three additional Leptomyrmex species. The annotation of the mitogenome and characterization of microsatellite markers will provide useful tools for assessing the colony structure, population genetic patterns, and dispersal strategy of L. pallens in the context of rainforest fragmentation in New Caledonia. Furthermore, this paper confirms a recent line of evidence that comprehensive mitochondrial data can be obtained relatively easily from small next-generation sequencing analyses. Greater synthesis of next-generation sequencing data will play a significant role in expanding the taxonomic representation of mitochondrial genome sequences.

Induction and reversal of myotonic dystrophy type 1 pre-mRNA splicing defects by small molecules.

The ability to control pre-mRNA splicing with small molecules could facilitate the development of therapeutics or cell-based circuits that control gene function. Myotonic dystrophy type 1 is caused by the dysregulation of alternative pre-mRNA splicing due to sequestration of muscleblind-like 1 protein (MBNL1) by expanded, non-coding r(CUG) repeats (r(CUG)(exp)). Here we report two small molecules that induce or ameliorate alternative splicing dysregulation. A thiophene-containing small molecule (1) inhibits the interaction of MBNL1 with its natural pre-mRNA substrates. Compound (2), a substituted naphthyridine, binds r(CUG)(exp) and displaces MBNL1. Structural models show that 1 binds MBNL1 in the Zn-finger domain and that 2 interacts with UU loops in r(CUG)(exp). This study provides a structural framework for small molecules that target MBNL1 by mimicking r(CUG)(exp) and shows that targeting MBNL1 causes dysregulation of alternative splicing, suggesting that MBNL1 is thus not a suitable therapeutic target for the treatment of myotonic dystrophy type 1.

Assessment and monitoring of nutrient loading in the sediments of tidal creeks receiving shrimp farm effluent in Quang Ninh, Vietnam.

Coastal shrimp farming may lead to the contamination of sediments of surrounding estuarine and marine ecosystems as shrimp farm effluent often contains high levels of pollutants including a range of organic compounds (from uneaten feed, shrimp feces, and living and dead organisms) which can accumulate in the sediments of receiving waterways. The assessment and monitoring of sediment quality in tidal creeks receiving shrimp farm effluent can support environmental protection and decision making for sustainable development in coastal areas since sediment quality often shows essential information on long-term aquatic ecosystem health. Within this context, this paper investigates nutrient loadings in the sediments of tidal creeks receiving shrimp farm effluent in Quang Ninh, Vietnam, which now have a high concentration of intensive and semi-intensive shrimp farms. Sediment samples taken from inside creek sections directly receiving effluent from concentrated shrimp farms (IEC), from main creeks adjacent to points of effluent discharge outside concentrated shrimp farms (OEC), and few kilometers away from shrimp farms (ASF) as reference sites were collected and analyzed before and after shrimp crops to investigate spatial and temporal variation. The results showed that there were statistically significant differences in the concentrations of total nitrogen, total phosphorus, and total organic carbon among IEC, OEC, and ASF sites while the seasonal variation being limited over study times. A sediment nutrient index (SNI) computed from coefficient scores of the factor analysis efficiently summarizes sediment nutrient loads, which are high, albeit quite variable, in canals directly receiving effluents from farms but then decline sharply with distance from shrimp farms. The visualization and monitoring of sediment quality data including SNI on maps can strongly support managers to manage eutrophication at concentrated shrimp farming areas, contributing to sustainable development and management at coastal zones.

A call for transparent reporting to optimize the predictive value of preclinical research.

The US National Institute of Neurological Disorders and Stroke convened major stakeholders in June 2012 to discuss how to improve the methodological reporting of animal studies in grant applications and publications. The main workshop recommendation is that at a minimum studies should report on sample-size estimation, whether and how animals were randomized, whether investigators were blind to the treatment, and the handling of data. We recognize that achieving a meaningful improvement in the quality of reporting will require a concerted effort by investigators, reviewers, funding agencies and journal editors. Requiring better reporting of animal studies will raise awareness of the importance of rigorous study design to accelerate scientific progress.

Identification of rays through DNA barcoding: an application for ecologists.

DNA barcoding potentially offers scientists who are not expert taxonomists a powerful tool to support the accuracy of field studies involving taxa that are diverse and difficult to identify. The taxonomy of rays has received reasonable attention in Australia, although the fauna in remote locations such as Ningaloo Reef, Western Australia is poorly studied and the identification of some species in the field is problematic. Here, we report an application of DNA-barcoding to the identification of 16 species (from 10 genera) of tropical rays as part of an ecological study. Analysis of the dataset combined across all samples grouped sequences into clearly defined operational taxonomic units, with two conspicuous exceptions: the Neotrygon kuhlii species complex and the Aetobatus species complex. In the field, the group that presented the most difficulties for identification was the spotted whiptail rays, referred to as the 'uarnak' complex. Two sets of problems limited the successful application of DNA barcoding: (1) the presence of cryptic species, species complexes with unresolved taxonomic status and intra-specific geographical variation, and (2) insufficient numbers of entries in online databases that have been verified taxonomically, and the presence of lodged sequences in databases with inconsistent names. Nevertheless, we demonstrate the potential of the DNA barcoding approach to confirm field identifications and to highlight species complexes where taxonomic uncertainty might confound ecological data.

Dose-response modeling of high-throughput screening data.

The National Toxicology Program is developing a high-throughput screening (HTS) program to set testing priorities for compounds of interest, to identify mechanisms of action, and potentially to develop predictive models for human toxicity. This program will generate extensive data on the activity of large numbers of chemicals in a wide variety of biochemical- and cell-based assays. The first step in relating patterns of response among batteries of HTS assays to in vivo toxicity is to distinguish between positive and negative compounds in individual assays. Here, the authors report on a statistical approach developed to identify compounds positive or negative in an HTS cytotoxicity assay based on data collected from screening 1353 compounds for concentration-response effects in 9 human and 4 rodent cell types. In this approach, the authors develop methods to normalize the data (removing bias due to the location of the compound on the 1536-well plates used in the assay) and to analyze for concentration-response relationships. Various statistical tests for identifying significant concentration-response relationships and for addressing reproducibility are developed and presented.

Posttraumatic stress disorder in older people after a fall.

BACKGROUND: Posttraumatic Stress Disorder (PTSD) is a debilitating psychological condition, never studied in relation to falls in older people. This study determines the prevalence and correlates of PTSD in older people post-fall. METHOD: A prospective survey study, with baseline data collected by interview in hospital post-fall and by postal self-completion at 12 and 24 weeks post-baseline. A convenience sample of 196 people (> or = 65 years) were serially recruited, 87.9% of those eligible. Information collected at baseline included falls-related data, activity problems, fear of falling, PTSD symptoms, anxiety and depression, and at follow-up PTSD symptoms, anxiety and depression, the receipt of rehabilitation and further falls. RESULTS: In hospital, of 40 participants whose fall had occurred over 1 month previously 35% had full acute PTSD and 17.5% had partial acute PTSD. At follow-up full or partial chronic PTSD was found in 26.1% of participants at first follow-up, and in 27.4% of participants at second follow-up. Older age, pre-fall activity problems, fear of falling, and anxiety assessed at baseline were associated (p < 0.05) with follow-up PTSD diagnosis, as were anxiety and depression assessed concurrently. CONCLUSION: PTSD occurs in a substantial minority of older people post-fall. No pattern emerged of factors predictive of PTSD, although the association between fear of falling and PTSD suggests some patients thought to have fear of falling may be manifesting PTSD, and require identification to enable therapeutic intervention.

Inhibition of indoleamine 2,3 dioxygenase activity by H2O2.

Indoleamine 2,3-dioxygenase is the first and rate limiting enzyme of the kynurenine pathway of tryptophan metabolism, has potent effects on cell proliferation and mediates antimicrobial, antitumorogenic, and immunosuppressive effects. As a potent cytotoxic effector, the mechanisms of indoleamine 2,3-dioxygenase inhibition deserve greater attention. The work presented here represents the first systematic study exploring the mechanisms by which low levels of hydrogen peroxide (10-100 microM) inhibit indoleamine 2,3-dioxygenase in vitro. Following brief peroxide exposure both enzyme inhibition and structural changes were observed. Loss of catalysis was accompanied by oxidation of several cysteine residues to sulfinic and sulfonic acids, observed by electrospray and MALDI mass spectrometry. Enzyme activity could in part be preserved in the presence of sulfhydryl containing compounds, particularly DTT and methionine. However, these structural alterations did not prevent substrate (l-tryptophan) binding. Some enzyme activity could be recovered in the presence of thioredoxin, indicating that the inhibitory effect of H(2)O(2) is at least partially reversible in vitro. We present evidence that cysteine oxidation represents one mechanism of indoleamine 2,3-dioxygenase inhibition.