Confronting the opioid crisis: Practical pain management and strategies: AOA 2018 critical issues symposium

The United States is in the midst of an opioid crisis. Clinicians have been part of the problem because of overprescribing of narcotics for perioperative pain management. Clinicians need to understand the pathophysiology and science of addiction to improve perioperative management of pain for their patients. Multiple modalities for pain management exist that decrease the use of narcotics. Physical strategies, cognitive strategies, and multimodal medication can all provide improved pain relief and decrease the use of narcotics. National medical societies are developing clinical practice guidelines for pain management that incorporate multimodal strategies and multimodal medication. Changes to policy that improve provider education, access to naloxone, and treatment for addiction can decrease narcotic misuse and the risk of addiction

Genetic variants in ARID5B and CEBPE are childhood ALL susceptibility loci in Hispanics.

Recent genome-wide studies conducted in European Whites have identified novel susceptibility genes for childhood acute lymphoblastic leukemia (ALL). We sought to examine whether these loci are susceptibility genes among Hispanics, whose reported incidence of childhood ALL is the highest of all ethnic groups in California, and whether their effects differ between Hispanics and non-Hispanic Whites (NHWs). We genotyped 13 variants in these genes among 706 Hispanic (300 cases, 406 controls) and 594 NHW (225 cases, 369 controls) participants in a matched population-based case-control study in California. We found significant associations for the five studied ARID5B variants in both Hispanics (p values of 1.0 × 10(-9) to 0.004) and NHWs (p values of 2.2 × 10(-6) to 0.018). Risk estimates were in the same direction in both groups (ORs of 1.53-1.99 and 1.37-1.84, respectively) and strengthened when restricted to B-cell precursor high-hyperdiploid ALL (>50 chromosomes; ORs of 2.21-3.22 and 1.67-2.71, respectively). Similar results were observed for the single CEBPE variant. Hispanics and NHWs exhibited different susceptibility loci at CDKN2A. Although IKZF1 loci showed significant susceptibility effects among NHWs (p < 1 × 10(-5)), their effects among Hispanics were in the same direction but nonsignificant, despite similar minor allele frequencies. Future studies should examine whether the observed effects vary by environmental, immunological, or lifestyle factors

Staged correction of an equinovarus deformity due to pyoderma gangrenosum using a Taylor spatial frame and tibiotalar calcaneal fusion with an intramedullary device

Pyoderma gangrenosum is a rare autoinflammatory syndrome manifested by skin lesions eventually creating ulcers. Surgical management can lead to scarring and contracture at the site of the lesion due to the pathergy phenomenon. A 43-year-old woman presented with a 5-year history of severe equinovarus deformity due to chronic pyoderma gangrenosum on her posteromedial ankle. She underwent a staged fusion. A gradual “closed” correction was performed in a Taylor spatial frame for 8 weeks in order to obviate the need for a surgical release in the area of the ulcer. She was ambulatory and full weight-bearing within 4 weeks of her frame removal. She maintained her correction with an accommodative foot orthosis until she had an uneventful tibiotalar calcaneal fusion with an intramedullary device. This case represents the success of using a Taylor spatial frame for staged fusion involving soft-tissue correction of severe, rigid equinovarus deformity due to pyoderma gangrenosum

Sulfite reduction in mycobacteria

Mycobacterium tuberculosis places an enormous burden on the welfare of humanity. Its ability to grow and its pathogenicity are linked to sulfur metabolism, which is considered a fertile area for the development of antibiotics, particularly because many of the sulfur acquisition steps in the bacterium are not found in the host. Sulfite reduction is one such mycobacterium-specific step and is the central focus of this paper. Sulfite reduction in Mycobacterium smegmatis was investigated using a combination of deletion mutagenesis, metabolite screening, complementation, and enzymology. The initial rate parameters for the purified sulfite reductase from M. tuberculosis were determined under strict anaerobic conditions [kcat = 1.0 (±0.1) electron consumed per second, and Km(SO3−2) = 27 (±1) μM], and the enzyme exhibits no detectible turnover of nitrite, which need not be the case in the sulfite/nitrite reductase family. Deletion of sulfite reductase (sirA, originally misannotated nirA) reveals that it is essential for growth on sulfate or sulfite as the sole sulfur source and, further, that the nitrite-reducing activities of the cell are incapable of reducing sulfite at a rate sufficient to allow growth. Like their nitrite reductase counterparts, sulfite reductases require a siroheme cofactor for catalysis. Rv2393 (renamed che1) resides in the sulfur reduction operon and is shown for the first time to encode a ferrochelatase, a catalyst that inserts Fe2+ into siroheme. Deletion of che1 causes cells to grow slowly on metabolites that require sulfite reductase activity. This slow-growth phenotype was ameliorated by optimizing growth conditions for nitrite assimilation, suggesting that nitrogen and sulfur assimilation overlap at the point of ferrochelatase synthesis and delivery

100-ps-pulse-duration, 100-J burst-mode laser for kHz–MHz flow diagnostics

A high-speed, master-oscillator power-amplifier burst-mode laser with ∼100 ps pulse duration is demonstrated with output energy up to 110 J per burst at 1064 nm and second-harmonic conversion efficiency up to 67% in a KD*P crystal. The output energy is distributed across 100 to 10,000 sequential laser pulses, with 10 kHz to 1 MHz repetition rate, respectively, over 10 ms burst duration. The performance of the 100 ps burst-mode laser is evaluated and been found to compare favorably with that of a similar design that employs a conventional ∼8 ns pulse duration. The nearly transform-limited spectral bandwidth of 0.15 cm−1 at 532 nm is ideal for a wide range of linear and nonlinear spectroscopic techniques, and the 100 picosecond pulse duration is optimal for fiber-coupled spectroscopic measurements in harsh reacting-flow environments

Metagenomic next-generation sequencing of samples from pediatric febrile illness in Tororo, Uganda.

Febrile illness is a major burden in African children, and non-malarial causes of fever are uncertain. In this retrospective exploratory study, we used metagenomic next-generation sequencing (mNGS) to evaluate serum, nasopharyngeal, and stool specimens from 94 children (aged 2-54 months) with febrile illness admitted to Tororo District Hospital, Uganda. The most common microbes identified were Plasmodium falciparum (51.1% of samples) and parvovirus B19 (4.4%) from serum; human rhinoviruses A and C (40%), respiratory syncytial virus (10%), and human herpesvirus 5 (10%) from nasopharyngeal swabs; and rotavirus A (50% of those with diarrhea) from stool. We also report the near complete genome of a highly divergent orthobunyavirus, tentatively named Nyangole virus, identified from the serum of a child diagnosed with malaria and pneumonia, a Bwamba orthobunyavirus in the nasopharynx of a child with rash and sepsis, and the genomes of two novel human rhinovirus C species. In this retrospective exploratory study, mNGS identified multiple potential pathogens, including 3 new viral species, associated with fever in Ugandan children

Organoid Imaging Strategies for Accelerating Translational Research

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