SARS-CoV-2 Related Ischemic Colitis in an Adolescent With Trisomy 21: Diagnostic Pitfalls and Considerations.

Millions of patients seek medical attention for diarrhea, vomiting, nausea, and abdominal pain. In the current environment, it is important to recognize that these symptoms may be the only manifestation or may precede more serious systemic complications of COVID-19. Herein, we describe the first case of ischemic colitis (IC) in a young adult who presented with diarrhea and highlight the laboratory pitfalls for patients with COVID-19 presenting with gastrointestinal (GI) symptoms.

Genetic structure and admixture in sheep from terminal breeds in the United States.

Selection for performance in diverse production settings has resulted in variation across sheep breeds worldwide. Although sheep are an important species to the United States, the current genetic relationship among many terminal sire breeds is not well characterized. Suffolk, Hampshire, Shropshire and Oxford (terminal) and Rambouillet (dual purpose) sheep (n = 248) sampled from different flocks were genotyped using the Applied Biosystems Axiom Ovine Genotyping Array (50K), and additional Shropshire sheep (n = 26) using the Illumina Ovine SNP50 BeadChip. Relationships were investigated by calculating observed heterozygosity, inbreeding coefficients, eigenvalues, pairwise Wright's FST estimates and an identity by state matrix. The mean observed heterozygosity for each breed ranged from 0.30 to 0.35 and was consistent with data reported in other US and Australian sheep. Suffolk from two different regions of the United States (Midwest and West) clustered separately in eigenvalue plots and the rectangular cladogram. Further, divergence was detected between Suffolk from different regions with Wright's FST estimate. Shropshire animals showed the greatest divergence from other terminal breeds in this study. Admixture between breeds was examined using admixture, and based on cross-validation estimates, the best fit number of populations (clusters) was K = 6. The greatest admixture was observed within Hampshire, Suffolk, and Shropshire breeds. When plotting eigenvalues, US terminal breeds clustered separately in comparison with sheep from other locations of the world. Understanding the genetic relationships between terminal sire breeds in sheep will inform us about the potential applicability of markers derived in one breed to other breeds based on relatedness.

Genome-wide association study to identify genetic loci associated with gastrointestinal nematode resistance in Katahdin sheep.

Resistance to gastrointestinal nematodes has previously been shown to be a moderately heritable trait in some breeds of sheep, but the mechanisms of resistance are not well understood. Selection for resistance currently relies upon faecal egg counts (FEC), blood packed cell volumes and FAMACHA visual indicator scores of anaemia. Identifying genomic markers associated with disease resistance would potentially improve the selection process and provide a more reliable means of classifying and understanding the biology behind resistant and susceptible sheep. A GWAS was conducted to identify possible genetic loci associated with resistance to Haemonchus contortus in Katahdin sheep. Forty animals were selected from the top and bottom 10% of estimated breeding values for FEC from a total pool of 641 sires and ram lambs. Samples were genotyped using Applied Biosystems™ Axiom™ Ovine Genotyping Array (50K) consisting of 51 572 SNPs. Following quality control, 46 268 SNPs were included in subsequent analyses. Analyses were conducted using a linear regression model in plink v1.90 and a single-locus mixed model in snp and variation suite. Genome-wide significance was determined by a Bonferroni correction for multiple testing. Using linear regression, loci on chromosomes 2, 3, 16, 23 and 24 were significantly associated at the genome level with FEC estimated breeding values, and we identified a region on chromosome 2 that was significant using both statistical analyses. We suggest a potential role for the gene DIS3L2 for gastrointestinal nematode resistance in Katahdin sheep, although further research is needed to validate these findings.

The effect of hypoglycaemia during hospital admission on health-related outcomes for people with diabetes: a systematic review and meta-analysis.

AIM: To assess the health-related outcomes of hypoglycaemia for people with diabetes admitted to hospital; specifically, hospital length of stay and mortality. METHODS: We conducted a systematic review and meta-analysis of studies relating to hypoglycaemia (< 4 mmol/l) for hospitalized adults (≥ 16 years) with diabetes reporting the primary outcomes of interest, hospital length of stay or mortality. Final papers for inclusion were reviewed in duplicate and the adjusted results of each were pooled, using a random effects model then undergoing further prespecified subgroup analysis. RESULTS: In total, 15 studies were included in the meta-analysis. The pooled mean difference in length of stay for ward-based inpatients exposed to hypoglycaemia was 4.1 days longer [95% confidence interval (CI) 2.36 to 5.79; I² = 99%] compared with those without hypoglycaemia. This association remained robust across the pre-specified subgroup analyses. The pooled relative risk (RR) of in-hospital mortality was greater for those exposed to hypoglycaemia (RR 2.09, 95% CI 1.64 to 2.67; I² = 94%, n = 7 studies) but not in intensive care unit mortality (RR 0.75, 95% CI 0.49 to 1.16; I² =0%, n = 2 studies). CONCLUSION: There is an association between inpatient hypoglycaemia and longer length of stay and greater in-hospital mortality. Studies examining this association were heterogenous in terms of both clinical populations and effect size, but the overall direction of the association was consistent. Therefore, glucose concentration should be considered a potential tool to aid the identification of inpatients at risk of poor health-related outcomes.

Effectiveness of a multidisciplinary team approach to the prevention of readmission for acute glycaemic events.

AIMS: To describe the effect of a combined diabetes specialist/mental health team approach to prevent readmissions for acute glycaemic events among patients with diabetes. METHODS: Consecutive patients with diabetes, readmitted to a single hospital for an acute glycaemic condition, were offered one or more diabetes (including assessment, education, medication, technology use and intensive support) and mental health (including assessment, training and therapies) interventions. The pilot service took place over 11 months, with the preceding 24 months and subsequent 8 months serving as control periods. RESULTS: Of the 58 patients admitted, 50 had Type 1 diabetes and were from within the hospital catchment area, and were discharged home. Of these, 32 (64%) had a pre-existing mental health issue and 14 (28%) had a complex social situation. In all, 96% of patients were met as an inpatient by a team member, and 94% accepted at least one intervention. The mean ±sd number of admissions per patient/month dropped from 0.12 ± 0.10 to 0.05 ± 0.10 (P < 0.001) during the intervention, increasing, once the intervention ended, to 0.16 ± 0.36 (P = 0.002). The mean ± sd length of stay similarly decreased and increased (0.6 ± 0.9 to 0.2 ± 0.7 days; P < 0.001 to 0.006) to 0.6 ± 1.4 days (P = 0.003) per patient/month) across the three periods, as did the mean ±sd tariff paid per patient/month (£258.0 ± 374.0 vs £92.1 ± 245.0 vs £287.3 ± 563.8; P < 0.001 and P = 0.018, respectively). The mean ± sd HbA1c level dropped from 99 ± 22 to 92 ± 24 mmol/mol (11.2 ± 4.2% vs 10.6 ± 4.3%; P = 0.014) but did not increase after the intervention [89 ± 26 mmol/mol (10.4 ± 4.5%)]. CONCLUSIONS: The cost and long-term risks of hospitalization among patients with Type 1 diabetes and recurrent admissions can be reduced by a combined specialist diabetes/mental health team approach.

Experience with endoscopy and endoscopy-assisted management of pediatric surgical problems: results and lessons.

Minimally invasive surgical techniques are becoming increasingly popular within the pediatric population. Flexible endoscopy may enhance or replace existing techniques in the future. Many of the reported benefits of laparoscopy and thoracoscopy may apply to endoscopy and endoscopy-assisted procedures; however, no reports exist as to the application, results, and outcomes for these procedures in children. It was hypothesized that endoscopy is a useful and safe adjunct for pediatric surgical patients. Retrospective review of medical records for patients who underwent endoscopy or endoscopy-assisted operations at two children's hospitals over 3 years (August 31, 2007-August 31, 2010) was completed. During this time period, 30 procedures were performed on 28 patients. Indications for procedure, age, operative technique, operative times, surgical outcomes, complications, and length of stay for each patient were reviewed. Patient age ranged from 3 days to 20 years. Indications for operation included esophageal pathology (13), gastroduodenal pathology (14), pancreatic pseudocyst (2), and displaced sigmoid Chait® (Cook, Inc., Bloomington, IN, USA) tube. Although endoscopy was intended only as an adjunct in all cases, the planned procedure was satisfactorily completed with a purely endoscopic approach in six cases. There were no intraoperative complications, and minor postoperative complications including one stricture requiring dilation, postoperative stridor, and esophageal leak, were each successfully managed conservatively. Endoscopy offers a promising adjunct to more traditional minimally invasive techniques in children. In some cases, endoscopy may offer an alternative to more invasive procedures or eliminate the need for tube thoracostomy or post-procedural contrast studies in some esophageal cases.

Review: Implantation and placentation in ruminants.

Ruminants have a unique placenta in comparison to other mammalian species. Initially, they possess a non-invasive epitheliochorial type of placenta during conceptus elongation. As the conceptus trophectoderm begins to attach to the luminal epithelium (LE) of the endometrium, binucleate cells (BNCs) develop within the trophoblast of the chorion. The BNCs migrate and fuse with the uterine LE to form multinucleate syncytial plaques in sheep and hybrid trinucleate cells in cattle. This area of the ruminant placenta is semi-invasive synepitheliochorial. The BNCs form the foundation of the placental cotyledons and express unique placenta-specific genes including pregnancy-associated glycoproteins and chorionic somatomammotropin hormone 2 or placental lactogen. Attachment and interdigitation of cotyledons into endometrial caruncles form placentomes that are subsequently vascularized to provide essential nutrients for growth of the fetus. This chapter review will discuss historical and current aspects of conceptus implantation and placenta development in ruminant ungulates with a focus on cattle and sheep. Single-cell analysis promises to provide a much more detailed understanding of the different cell populations and insights into pathways mediating trophoblast and placenta. This fundamental is required to understand pregnancy loss and develop strategies to improve pregnancy outcomes in ruminants.

Augmented environments for minimally invasive therapy: implementation barriers from technology to practice.

Augmented environments for medical applications have been explored and developed in an effort to enhance the clinician's view of anatomy and facilitate the performance of minimally invasive procedures. These environments must faithfully represent the real surgical field and require seamless integration of pre- and intra-operative imaging, surgical instrument tracking and display technology into a common framework centered around the patient. However, few image guidance environments have been successfully translated into clinical use. Several challenges that contribute to the slow progress of integrating such environments into clinical practice are discussed here in terms of both technical and clinical limitations.

Nuclear Genome Assembly of the Microalga Nannochloropsis salina CCMP1776.

Nannochloropsis salina is a halotolerant, high-lipid-producing microalga that is being explored as a biofuel production species. Here, we report an improved high-quality draft assembly and annotation for the nuclear genome of N. salina strain CCMP1776.

MAP kinase pathways in the yeast Saccharomyces cerevisiae.

A cascade of three protein kinases known as a mitogen-activated protein kinase (MAPK) cascade is commonly found as part of the signaling pathways in eukaryotic cells. Almost two decades of genetic and biochemical experimentation plus the recently completed DNA sequence of the Saccharomyces cerevisiae genome have revealed just five functionally distinct MAPK cascades in this yeast. Sexual conjugation, cell growth, and adaptation to stress, for example, all require MAPK-mediated cellular responses. A primary function of these cascades appears to be the regulation of gene expression in response to extracellular signals or as part of specific developmental processes. In addition, the MAPK cascades often appear to regulate the cell cycle and vice versa. Despite the success of the gene hunter era in revealing these pathways, there are still many significant gaps in our knowledge of the molecular mechanisms for activation of these cascades and how the cascades regulate cell function. For example, comparison of different yeast signaling pathways reveals a surprising variety of different types of upstream signaling proteins that function to activate a MAPK cascade, yet how the upstream proteins actually activate the cascade remains unclear. We also know that the yeast MAPK pathways regulate each other and interact with other signaling pathways to produce a coordinated pattern of gene expression, but the molecular mechanisms of this cross talk are poorly understood. This review is therefore an attempt to present the current knowledge of MAPK pathways in yeast and some directions for future research in this area.

Draft Nuclear Genome, Complete Chloroplast Genome, and Complete Mitochondrial Genome for the Biofuel/Bioproduct Feedstock Species Scenedesmus obliquus Strain DOE0152z.

The green alga Scenedesmus obliquus is an emerging platform species for the industrial production of biofuels. Here, we report the draft assembly and annotation for the nuclear, plastid, and mitochondrial genomes of S. obliquus strain DOE0152z.

Draft Genomes for Eight Burkholderia mallei Isolates from Turkey.

Burkholderia mallei, the etiologic agent of glanders, is a Gram-negative, nonmotile, facultative intracellular pathogen. Although glanders has been eradicated from many parts of the world, the threat of B. mallei being used as a weapon is very real. Here we present draft genome assemblies of 8 Burkholderia mallei strains that were isolated in Turkey.

Metabolic aspects of the secretion of stored compounds from blood platelets. IV. Effects of ionophore X537A on washed platelets.

1. X537A at concentrations below 10 muM can liberate platelet serotonin from washed human platelets without inducing the platelet release reaction. Up to 100% of serotonin preabsorbed by the platelets can be liberated before initiation of the release reaction. 2. Concentrations of X537A above 10muM initiate the platelet release reaction, with a maximum release of adenine nucleotides and platelet factor 4 antigen comparable to that obtained with 1.25 units thrombin/ml. 3. The changes in ATP metabolism at the concentration necessary for X537A-induced release are more profound than those in platelets exposed to concentrations of thrombin or A23187 giving the same degree of release, and approach those seen with high concentrations of A23187. At concentrations where serotonin is liberated but no adenine nucleotide or platelet factor 4 antigen is released, short time incubation causes no change in the level of metabolic ATP.

Metabolic aspects of the secretion of stored compounds from blood platelets. V. Effect of ionophore A23187 on washed platelets.

1. The A23187-induced secretion of preabsorbed serotonin from human blood platelets at 37 degrees C is studied. Preincubation at the same temperature before the addition of ionophore is necessary for maximal release induction. When total incubation time is kept constant, longer time with ionophore results in a smaller decrease in the level of metabolic ATP and increase in metabolic ATP and increase in metabolic IMP. This coincides with the reduction in secretion, but statistical treatment of the results suggests that the reduced secretion only partially explains the reduced drop in metabolic ATP, and that therefore a resynthesis of metabolic ATP from IMP may have taken place. 2. In some experiments induction of secretion takes place over a very narrow range of ionophore concentration. 3. When K+ substitutes for Na+ in the extracellular medium, the need for preincubation for maximal secretion becomes less evident, and at times is abolished, while there is still a significant increase in the metabolic ATP level by prolonged incubation with ionophore. 4. A reduction in secretion is observed with metabolic blockers when the ionophore is added after preincubation, but to a much less degree than when secretion is induced by thrombin, in spite of a great reduction in the level of metabolic ATP. This may partly be explained by the increase in secretion induction by A23187 in the presence of inhibitors when the ionophore is added in the cold, suggesting that the inhibitor may cause "weakening" of the platelets' "resistance" to induction of secretion by ionophore. 5. When the effect of Ca2+ and of Mg2+ on the level of intermediates of the TP leads to hypoxanthine conversion is studied, it is evident that the addition of Ca2+ causes enhanced IMP accumulation and a reduction in the level of inosine plus hypoxanthine, while Mg2+ has the opposite effect. This suggests that the two metals affect the enzymes of the IMP leads to hypoxanthine conversion differently. 6. Indomethacin inhibits secretion induced by A23187, suggesting that prostaglandin intermediates may amplify the ionophore-induced release. The adenine nucleotide metabolism is not affected. 7. The results indicate that there is an indirect, rather than direct, link between the major metabolic changes and the secretion induced by A23187, but that the ionophore may cause intracellular changes which are not connected to its effect as release inducer.

Activation of the Saccharomyces cerevisiae filamentation/invasion pathway by osmotic stress in high-osmolarity glycogen pathway mutants.

Mitogen-activated protein kinase (MAPK) cascades are frequently used signal transduction mechanisms in eukaryotes. Of the five MAPK cascades in Saccharomyces cerevisiae, the high-osmolarity glycerol response (HOG) pathway functions to sense and respond to hypertonic stress. We utilized a partial loss-of-function mutant in the HOG pathway, pbs2-3, in a high-copy suppressor screen to identify proteins that modulate growth on high-osmolarity media. Three high-copy suppressors of pbs2-3 osmosensitivity were identified: MSG5, CAK1, and TRX1. Msg5p is a dual-specificity phosphatase that was previously demonstrated to dephosphorylate MAPKs in yeast. Deletions of the putative MAPK targets of Msg5p revealed that kss1delta could suppress the osmosensitivity of pbs2-3. Kss1p is phosphorylated in response to hyperosmotic shock in a pbs2-3 strain, but not in a wild-type strain nor in a pbs2-3 strain overexpressing MSG5. Both TEC1 and FRE::lacZ expressions are activated in strains lacking a functional HOG pathway during osmotic stress in a filamentation/invasion-pathway-dependent manner. Additionally, the cellular projections formed by a pbs2-3 mutant on high osmolarity are absent in strains lacking KSS1 or STE7. These data suggest that the loss of filamentation/invasion pathway repression contributes to the HOG mutant phenotype.

Evidence for the use of silver-alloy-coated urethral catheters.

Catheter-associated urinary tract infections (CAUTIs) are a common occurrence and are associated with increased patient morbidity and mortality. In addition, they delay patient discharge from hospital, substantially increase hospital costs and promote the emergence of resistant organisms. Any intervention resulting in a decrease in the incidence of CAUTIs would have a significant impact on patient quality of life and hospital costs. By reviewing the current literature, it can be seen that the use of silver-alloy-coated hydrogel catheters can reduce CAUTIs by up to 45%. Despite reducing CAUTIs in most hospital situations, the greatest reduction is seen in postoperative patients, intensive care unit patients and burns patients.

Complete Genome Assemblies for Two Single-Chromosome Vibrio cholerae Isolates, Strains 1154-74 (Serogroup O49) and 10432-62 (Serogroup O27).

Here, we report the completed genome sequences for two non-O1/non-O139 Vibrio cholerae isolates. Each isolate has only a single chromosome, as opposed to the normal paradigm of two chromosomes found in all other V. cholerae isolates.

Antibiotics delivered by an implantable drug pump. A new application for treating osteomyelitis.

Osteomyelitis is usually treated with wide surgical debridement and prolonged intravenous antibiotics. The advent of the implantable drug pump has led us to evaluate this therapeutic modality for the treatment of osteomyelitis. We have previously shown that amikacin retains microbiologic activity in an implantable drug pump over a six-week period when incubated at 37 degrees C. We have also demonstrated in rabbits that high local levels and low systemic levels of antibiotic can be achieved using an implantable drug pump as a delivery system and that this method can be used to sterilize infected wounds. This method was applied in the treatment of osteomyelitis in 14 patients whose duration of symptoms ranged from one month to 22 years. In 13 patients, active drainage had been present for more than six months, and all patients had undergone one or more attempts at eradication of their infection. Prior therapy included surgical debridement alone (one patient), one or more attempts at debridement and extended intravenous antibiotic therapy (13 patients), debridement and local flap procedures (four patients), and extended oral antibiotic therapy (two patients). The bones involved were the tibia (six patients), femur (four patients), and elbow, shoulder, hip, and radius (one patient each). Intra-operative cultures indicated that the infecting organism was Staphylococcus aureus alone (seven patients), S. aureus in combination with gram-negative bacteria (five patients), or gram-negative organisms alone (two patients). Debridement and pump implantation were performed in one stage. On an outpatient basis, the pumps were filled with amikacin in a concentration determined by each patient's serum level. Duration of therapy was based upon cessation of drainage and erythrocyte sedimentation rate. During therapy, serum amikacin levels ranged from less than 2.5 micrograms/ml to 8.2 micrograms/ml. The amikacin concentration in the wound drainage was always greater than the upper limits of what could be measured (greater than 55 micrograms/ml to greater than 5,000 micrograms/ml). There were no cases of ototoxicity and one case of minimal renal toxicity (posttreatment creatinine clearance of 66 ml per minute; normal equal to 70 ml per minute). Length of therapy ranged from 32 to 140 days (mean equal to 63 days). Length of hospitalization ranged from five to 52 days (mean equal to 24 days). Drainage in all patients stopped during therapy, but resumed in three patients after pump removal--in two patients, for brief periods of time, and in one patient, it continues. Twelve patients have posttreatment erythrocyte sedimentation rates less than or equal to 20 mm per hour.(ABSTRACT TRUNCATED AT 400 WORDS)

Ultrasonographic features of carotid plaque and the risk of subsequent neurologic deficits.

In a prospective study, 214 consecutive patients considered not to be candidates for surgical intervention were evaluated by means of duplex scanning. Of the patients, 135 had no symptoms and 79 had a history of previous neurologic symptoms. In 139 sides duplex scanning demonstrated nonhemodynamic stenosis (lumen diameter reduction, less than 50%) and in 99 sides, hemodynamic stenosis (lumen diameter reduction, 50% or greater). Of the 238 carotid artery plaques examined, 167 were homogenous and 71 were heterogenous. During a mean follow-up of 34 months, 27 new focal neurologic deficits occurred. Patients with previous symptoms had a higher incidence of new deficits (18/79 vs 9/135) (p less than 0.01). The severity of the stenosis and the presence of a heterogenous plaque were statistically correlated with the occurrence of new deficits (p less than 0.001). Multivariate analysis showed that the ultrasonographic pattern and the severity of the stenosis were independent variables. We conclude that a heterogenous plaque should be considered an unstable plaque with the possibility of causing cerebral ischemia.