Long-term Assessment of Post-Treatment Symptoms in Patients With Culture-Confirmed Early Lyme Disease.

Background: Lyme disease patients with erythema migrans are said to have post-treatment Lyme disease symptoms (PTLDS) if there is persistence of subjective symptoms for at least 6 months following antibiotic treatment and resolution of the skin lesion. The purpose of this study was to characterize PTLDS in patients with culture-confirmed early Lyme disease followed for >10 years.

Methods: Adult patients with erythema migrans with a positive skin or blood culture for Borrelia burgdorferi were enrolled in a prospective study beginning in 1991 and followed up at 6 months and annually thereafter to determine the long-term outcome of this infection.

Systemic Administration of Human Bone Marrow-Derived Mesenchymal Stromal Cell Extracellular Vesicles Ameliorates Aspergillus Hyphal Extract-Induced Allergic Airway Inflammation in Immunocompetent Mice.

Unlabelled: An increasing number of studies demonstrate that administration of either conditioned media (CM) or extracellular vesicles (EVs) released by mesenchymal stromal cells (MSCs) derived from bone marrow and other sources are as effective as the MSCs themselves in mitigating inflammation and injury. The goal of the current study was to determine whether xenogeneic administration of CM or EVs from human bone marrow-derived MSCs would be effective in a model of mixed Th2/Th17, neutrophilic-mediated allergic airway inflammation, reflective of severe refractory asthma, induced by repeated mucosal exposure to Aspergillus hyphal extract (AHE) in immunocompetent C57Bl/6 mice. Systemic administration of both CM and EVs isolated from human and murine MSCs, but not human lung fibroblasts, at the onset of antigen challenge in previously sensitized mice significantly ameliorated the AHE-provoked increases in airway hyperreactivity (AHR), lung inflammation, and the antigen-specific CD4 T-cell Th2 and Th17 phenotype.

Transvaginal cervical length scans to prevent prematurity in twins: a randomized controlled trial.

Background: Twin pregnancies are associated with an increased risk of perinatal morbidity and mortality primarily due to spontaneous preterm deliveries. The mean gestational age for delivery is 35.3 weeks and twins account for 23% of preterm births <32 weeks.

A Randomized Trial of Intrapartum Fetal ECG ST-Segment Analysis.

Background: It is unclear whether using fetal electrocardiographic (ECG) ST-segment analysis as an adjunct to conventional intrapartum electronic fetal heart-rate monitoring modifies intrapartum and neonatal outcomes.

Methods: We performed a multicenter trial in which women with a singleton fetus who were attempting vaginal delivery at more than 36 weeks of gestation and who had cervical dilation of 2 to 7 cm were randomly assigned to "open" or "masked" monitoring with fetal ST-segment analysis. The masked system functioned as a normal fetal heart-rate monitor.

INSECT PHYLOGENOMICS. Response to Comment on "Phylogenomics resolves the timing and pattern of insect evolution".

Tong et al. comment on the accuracy of the dating analysis presented in our work on the phylogeny of insects and provide a reanalysis of our data. They replace log-normal priors with uniform priors and add a "roachoid" fossil as a calibration point.

Nitric Oxide Up-Regulates RUNX2 in LNCaP Prostate Tumours: Implications for Tumour Growth In Vitro and In Vivo.

Aberrant expression of the transcription factor RUNX2 in prostate cancer has a number of important consequences including increased resistance to apoptosis, invasion and metastasis to bone. We previously demonstrated that hypoxia up-regulated RUNX2 in tumour cells, which in turn up-regulated the anti-apoptotic factor Bcl-2. Here, we investigate the impact of nitric oxide (NO) on RUNX2 and Bcl-2 expression in prostate cancer and further, how RUNX2 over-expression can impact tumour growth, angiogenesis and oxygenation in vivo.

Freshly thawed and continuously cultured human bone marrow-derived mesenchymal stromal cells comparably ameliorate allergic airways inflammation in immunocompetent mice.

Unlabelled: Recent data suggest that freshly thawed previously frozen mesenchymal stromal cells (MSCs) may not have the same effectiveness or breadth of anti-inflammatory activities as do continuously cultured MSCs. This has significant implications for clinical use, in which many infusion schemes use frozen cells thawed at the bedside for administration. The available data, however, predominantly evaluate in vitro MSC properties, and so far there has been limited in vivo analysis.

Long-term assessment of health-related quality of life in patients with culture-confirmed early Lyme disease.

The health-related quality of life of 100 subjects with culture-confirmed early Lyme disease enrolled in a prospective study with annual follow-up visits was evaluated using the 36-Item Short Form General Health Survey version 2 (SF-36v2) questionnaire at 11-20 years after diagnosis. The mean summary scores of physical and mental health were similar to those of the general population.

New World Tryptamine Hallucinogens and the Neuroscience of Ayahuasca.

New World indigenous peoples are noted for their sophisticated use of psychedelic plants in shamanic and ethnomedical practices. The use of psychedelic plant preparations among New World tribes is far more prevalent than in the Old World. Yet, although these preparations are botanically diverse, almost all are chemically similar in that their active principles are tryptamine derivatives, either DMT or related constituents.

Design and implementation of the START (STem cells for ARDS Treatment) trial, a phase 1/2 trial of human mesenchymal stem/stromal cells for the treatment of moderate-severe acute respiratory distress syndrome.

Background: Despite advances in supportive care, moderate-severe acute respiratory distress syndrome (ARDS) is associated with high mortality rates, and novel therapies to treat this condition are needed. Compelling pre-clinical data from mouse, rat, sheep and ex vivo perfused human lung models support the use of human mesenchymal stem (stromal) cells (MSCs) as a novel intravenous therapy for the early treatment of ARDS.

Methods: This article describes the study design and challenges encountered during the implementation and phase 1 component of the START (STem cells for ARDS Treatment) trial, a phase 1/2 trial of bone marrow-derived human MSCs for moderate-severe ARDS.

Mesenchymal stem (stromal) cells for treatment of ARDS: a phase 1 clinical trial.

Background: No effective pharmacotherapy for acute respiratory distress syndrome (ARDS) exists, and mortality remains high. Preclinical studies support the efficacy of mesenchymal stem (stromal) cells (MSCs) in the treatment of lung injury. We aimed to test the safety of a single dose of allogeneic bone marrow-derived MSCs in patients with moderate-to-severe ARDS.

Postthaw characterization of umbilical cord blood: markers of storage lesion.

Background: The continued growth in the uses of umbilical cord blood (UCB) will require the development of meaningful postthaw quality assays. This study examines both conventional and new measures for assessing UCB quality after long-term storage.

Study Design And Methods: The first arm of the study involved thawing UCB in storage for short (approx.

Functional genomics and microbiome profiling of the Asian longhorned beetle (Anoplophora glabripennis) reveal insights into the digestive physiology and nutritional ecology of wood feeding beetles.

Background: Wood-feeding beetles harbor an ecologically rich and taxonomically diverse assemblage of gut microbes that appear to promote survival in woody tissue, which is devoid of nitrogen and essential nutrients. Nevertheless, the contributions of these apparent symbionts to digestive physiology and nutritional ecology remain uncharacterized in most beetle lineages.

Results: Through parallel transcriptome profiling of beetle- and microbial- derived mRNAs, we demonstrate that the midgut microbiome of the Asian longhorned beetle (Anoplophora glabripennis), a member of the beetle family Cerambycidae, is enriched in biosynthetic pathways for the synthesis of essential amino acids, vitamins, and sterols.

Long-Term Assessment of Fibromyalgia in Patients with Culture-Confirmed Lyme Disease.

Background: Fibromyalgia occurs in 2% to 8% of the general population. One of the triggers may be Lyme disease. Methods: Patients with culture-confirmed Lyme disease who originally presented with erythema migrans have been evaluated annually in a prospective study to determine their long-term outcome.

Clinical mesenchymal stromal cell products undergo functional changes in response to freezing.

Background Aims: Current methods of mesenchymal stromal cell (MSC) cryopreservation result in variable post-thaw recovery and phenotypic changes caused by freezing. The objective of this investigation was to determine the influence of ex vivo cell expansion on phenotype of MSCs and the response of resulting phenotypes to freezing and thawing.

Methods: Human bone marrow aspirate was used.

A reproducible immunopotency assay to measure mesenchymal stromal cell-mediated T-cell suppression.

Background Aims: The T-cell suppressive property of bone marrow-derived mesenchymal stromal cells (MSCs) has been considered a major mode of action and basis for their utilization in a number of human clinical trials. However, there is no well-established reproducible assay to measure MSC-mediated T-cell suppression.

Methods: At the University of Wisconsin-Madison Production Assistance for Cellular Therapy (PACT) Center, we developed an in vitro quality control T-cell suppression immunopotency assay (IPA) that uses anti-CD3 and anti-CD28 antibodies to stimulate T-cell proliferation.

Long-term assessment of fatigue in patients with culture-confirmed Lyme disease.

Background: Fatigue is a common symptom with numerous causes. Severe fatigue is thought to be an important manifestation of post-treatment Lyme disease syndrome. The frequency with which severe fatigue occurs as a long-term sequela in prospectively followed patients with Lyme disease is unknown.

Phylogenomics resolves the timing and pattern of insect evolution.

Insects are the most speciose group of animals, but the phylogenetic relationships of many major lineages remain unresolved. We inferred the phylogeny of insects from 1478 protein-coding genes. Phylogenomic analyses of nucleotide and amino acid sequences, with site-specific nucleotide or domain-specific amino acid substitution models, produced statistically robust and congruent results resolving previously controversial phylogenetic relations hips.

What is wrong with the training of general surgery?

The practice of surgery has undergone tumultuous changes over the last 30 years. Disease management, trauma volume, operative techniques, supervision requirements, and allocation of work hours have all changed, resulting in a substantial impact on general surgical training. Changes need to occur in the structure, assessment, and mentorship of future residents to prepare them to enter the marketplace and practice safe medicine with confidence and authority.

Impact of long-term cryopreservation on single umbilical cord blood transplantation outcomes.

Umbilical cord blood (UCB) may be collected and cryopreserved for years before use. In vitro and murine models suggest that the duration of storage does not affect UCB progenitor cell performance; however, the impact of UCB age on clinical outcomes has not been definitely defined. This study sought to determine the effect of UCB unit cryopreservation time on hematopoietic potency.

Laparoscopic sleeve gastrectomy is safe and effective in elderly patients: a comparative analysis.

Background: Laparoscopic sleeve gastrectomy (SG) is gaining widespread popularity as a definitive bariatric operation that provides satisfactory and durable weight loss as well as comorbidity resolution. Although SG is being increasingly offered to patients of all ages, there is a paucity of reported outcomes in patients ≥62 years of age. The purpose of this study was to perform a comparative analysis of the outcomes of SG in patients >62 years versus a younger age group, with an emphasis on safety and efficacy.

Laparoscopic transgastric gastroplasty: a novel technique for a large esophagogastric fistula.

Esophagogastric fistula is a rare complication related to severe inflammation at the gastroesophageal junction. Most causes are related to severe gastroesophageal reflux disease, previous surgery, or malignancy. This is the case of a 72-year-old man who had a laparoscopic Nissen fundoplication.