Gonococcal osteomyelitis in a pediatric patient with disseminated gonococcal infection: Implications for antimicrobial management

© 2020 The Authors We report a case of a female teenager with gonococcal septic arthritis of the right shoulder that also caused osteomyelitis of the humeral head. Infection with Neisseria gonorrhoeae is a frequently diagnosed sexually transmitted infection in the sexually active teenage population and disseminated gonococcal infection (DGI) is the most common systemic manifestation of acute gonorrhea. DGI commonly involves acute arthritis, tenosynovitis and dermatitis with less common complications of endocarditis, hepatitis and meningitis. In contrast, osteomyelitis has only rarely been reported as a result of gonococcal infection. Clinicians need to be aware of this unusual manifestation of DGI as a prolonged duration of antimicrobial treatment may be needed to assure complete resolution of this infection

The impact of confirmed coronavirus disease 2019 (COVID-19) infection on ambulatory procedures and associated delays in care for asymptomatic patients

© 2021 Elsevier Inc. Background: Since the reopening of ambulatory centers, minimal data has been reported regarding positive tests among patients undergoing ambulatory procedures, associated delays in care, and outcomes of patients previously positive for coronavirus disease 2019. Methods: A retrospective observational case series of ambulatory procedures was performed. Records since the reopening of ambulatory centers in New York were searched for patients with positive coronavirus disease 2019 nasal swab results who underwent ambulatory procedures. Chart reviews were conducted to determine coronavirus disease history and hospitalizations, demographic information, procedure details, and 30-day admissions. Results: A total of 3,762 patients underwent ambulatory procedures. Of those, 53 were previously diagnosed with coronavirus disease 2019 but recovered and tested negative at preprocedural testing. Of the 3,709 asymptomatic patients, 37 (1.00%) tested positive during preprocedural testing; 21 patients had their procedures delayed on average 28.6 days until testing negative, while 16 had their procedures performed before testing negative owing to the time sensitivity of the procedure. There were no major complications or 30-day admissions in any of these asymptomatic patients. Three patients tested positive for coronavirus disease after having an ambulatory procedure. Conclusion: Positive tests in asymptomatic patients led to procedure delays of 28.6 days. No patients who underwent ambulatory procedures after a positive coronavirus disease 2019 test had any coronavirus disease-related complications, regardless of whether or not the procedure was delayed until testing negative. Three patients tested positive for coronavirus disease 2019 after having an ambulatory procedure; however, at an average of 19.7 days after, these cases were likely community acquired making the rate of nosocomial infection negligible

An extremal effective survey about extremal effective cycles in moduli spaces of curves

We survey recent developments and open problems about extremal effective divisors and higher codimension cycles in moduli spaces of curves.Comment: Submitted to the Proceedings of the Abel Symposium 2017. Comments are welcom

Green tea polyphenol treatment is chondroprotective, anti-inflammatory and palliative in a mouse posttraumatic osteoarthritis model

Introduction Epigallocatechin 3-gallate (EGCG), a polyphenol present in green tea, was shown to exert chondroprotective effects in vitro. In this study, we used a posttraumatic osteoarthritis (OA) mouse model to test whether EGCG could slow the progression of OA and relieve OA-associated pain. Methods C57BL/6 mice were subjected to surgical destabilization of the medial meniscus (DMM) or sham surgery. EGCG (25 mg/kg) or vehicle control was administered daily for 4 or 8 weeks by intraperitoneal injection starting on the day of surgery. OA severity was evaluated using Safranin O staining and Osteoarthritis Research Society International (OARSI) scores, as well as by immunohistochemical analysis to detect cleaved aggrecan and type II collagen and expression of proteolytic enzymes matrix metalloproteinase 13 (MMP-13) and A disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5). Real-time PCR was performed to characterize the expression of genes critical for articular cartilage homeostasis. During the course of the experiments, tactile sensitivity testing (von Frey test) and open-field assays were used to evaluate pain behaviors associated with OA, and expression of pain expression markers and inflammatory cytokines in the dorsal root ganglion (DRG) was determined by real-time PCR. Results Four and eight weeks after DMM surgery, the cartilage in EGCG-treated mice exhibited less Safranin O loss and cartilage erosion, as well as lower OARSI scores compared to vehicle-treated controls, which was associated with reduced staining for aggrecan and type II collagen cleavage epitopes, and reduced staining for MMP-13 and ADAMTS5 in the articular cartilage. Articular cartilage in the EGCG-treated mice also exhibited reduced levels of Mmp1, Mmp3, Mmp8, Mmp13,Adamts5, interleukin 1 beta (Il1b) and tumor necrosis factor alpha (Tnfa) mRNA and elevated gene expression of the MMP regulator Cbp/p300 interacting transactivator 2 (Cited2). Compared to vehicle controls, mice treated with EGCG exhibited reduced OA-associated pain, as indicated by higher locomotor behavior (that is, distance traveled). Moreover, expression of the chemokine receptor Ccr2 and proinflammatory cytokines Il1b and Tnfa in the DRG were significantly reduced to levels similar to those of sham-operated animals. Conclusions This study provides the first evidence in an OA animal model that EGCG significantly slows OA disease progression and exerts a palliative effect. Electronic supplementary material The online version of this article (doi:10.1186/s13075-014-0508-y) contains supplementary material, which is available to authorized users

Serum IGF-1 is insufficient to restore skeletal size in the total absence of the growth hormone receptor

States of growth hormone (GH) resistance, such those observed in Laron dwarf patients, are characterized by mutations in the GH receptor (GHR), decreased serum and tissue IGF-1 levels, impaired glucose tolerance, and impaired skeletal acquisition. IGF-1 replacement therapy in such patients increases growth velocity but does not normalize growth. Herein we combined the GH-resistant (GHR knockout [GHRKO]) mouse model with mice expressing the hepatic Igf-1 transgene (HIT) to generate the GHRKO-HIT mouse model. In GHRKO-HIT mice, serum IGF-1 levels were restored via transgenic expression of Igf-1, allowing us to study how endocrine IGF-1 affects growth, metabolic homeostasis, and skeletal integrity. We show that in a GH-resistant state, normalization of serum IGF-1 improved body adiposity and restored glucose tolerance but was insufficient to support normal skeletal growth, resulting in an osteopenic skeletal phenotype. The inability of serum IGF-1 to restore skeletal integrity in the total absence of GHR likely resulted from reduced skeletal Igf-1 gene expression, blunted GH-mediated effects on the skeleton that are independent of serum or tissue IGF-1, and poor delivery of IGF-1 to the tissues. These findings are consistent with clinical data showing that IGF-I replacement therapy in patients with Laron syndrome does not achieve full skeletal growth.Fil: Wu, Yingjie. University Of New York; Estados UnidosFil: Sun, Hui. University Of New York; Estados UnidosFil: Basta Pljakic, Jelena. City College of New York; Estados UnidosFil: Cardoso, Luis. City College of New York; Estados UnidosFil: Kennedy, Oran D.. City College of New York; Estados UnidosFil: Jasper, Hector Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; ArgentinaFil: Domene, Horacio Mario. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; ArgentinaFil: Karabatas, Liliana Margarita. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; ArgentinaFil: Guida, María Clara. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; ArgentinaFil: Schaffler, Mitchell B.. City College of New York; Estados UnidosFil: Rosen, Clifford J.. Maine Medical Center Research Institute; Estados UnidosFil: Yakar, Shoshana. University Of New York; Estados Unido

Transient peak-strain matching partially recovers the age-impaired mechanoadaptive cortical bone response

Mechanoadaptation maintains bone mass and architecture; its failure underlies age-related decline in bone strength. It is unclear whether this is due to failure of osteocytes to sense strain, osteoblasts to form bone or insufficient mechanical stimulus. Mechanoadaptation can be restored to aged bone by surgical neurectomy, suggesting that changes in loading history can rescue mechanoadaptation. We use non-biased, whole-bone tibial analyses, along with characterisation of surface strains and ensuing mechanoadaptive responses in mice at a range of ages, to explore whether sufficient load magnitude can activate mechanoadaptation in aged bone. We find that younger mice adapt when imposed strains are lower than in mature and aged bone. Intriguingly, imposition of short-term, high magnitude loading effectively primes cortical but not trabecular bone of aged mice to respond. This response was regionally-matched to highest strains measured by digital image correlation and to osteocytic mechanoactivation. These data indicate that aged bone’s loading response can be partially recovered, non-invasively by transient, focal high strain regions. Our results indicate that old murine bone does respond to load when the loading is of sufficient magnitude, and bones’ age-related adaptation failure may be due to insufficient mechanical stimulus to trigger mechanoadaptation

Reductions in serum IGF-1 during aging impair health span

In lower or simple species, such as worms and flies, disruption of the insulin-like growth factor (IGF)-1 and the insulin signaling pathways has been shown to increase lifespan. In rodents, however, growth hormone (GH) regulates IGF-1 levels in serum and tissues and can modulate lifespan via/or independent of IGF- 1. Rodent models, where the GH/IGF-1 axis was ablated congenitally, show increased lifespan. However, in contrast to rodents where serum IGF-1 levels are high throughout life, in humans, serum IGF-1 peaks during puberty and declines thereafter during aging. Thus, animal models with congenital disruption of the GH/ IGF-1 axis are unable to clearly distinguish between developmental and age-related effects of GH/IGF-1 on health. To overcome this caveat, we developed an inducible liver IGF-1- deficient (iLID) mouse that allows temporal control of serum IGF- 1. Deletion of liver Igf -1 gene at one year of age reduced serum IGF-1 by 70% and dramatically impaired health span of the iLID mice. Reductions in serum IGF-1 were coupled with increased GH levels and increased basal STAT5B phosphorylation in livers of iLID mice. These changes were associated with increased liver weight, increased liver inflammation, increased oxidative stress in liver and muscle, and increased incidence of hepatic tumors. Lastly, despite elevations in serum GH, low levels of serum IGF-1 from 1 year of age compromised skeletal integrity and accelerated bone loss. We conclude that an intact GH/IGF-1 axis is essential to maintain health span and that elevated GH, even late in life, associates with increased pathology

BMP-12 Treatment of Adult Mesenchymal Stem Cells In Vitro Augments Tendon-Like Tissue Formation and Defect Repair In Vivo

We characterized the differentiation of rat bone marrow-derived mesenchymal stem cells (BM-MSCs) into tenocyte-like cells in response to bone morphogenetic protein-12 (BMP-12). BM-MSCs were prepared from Sprague-Dawley rats and cultured as monolayers. Recombinant BMP-12 treatment (10 ng/ml) of BM-MSCs for 12 hours in vitro markedly increased expression of the tenocyte lineage markers scleraxis (Scx) and tenomodulin (Tnmd) over 14 days. Treatment with BMP-12 for a further 12-hour period had no additional effect. Colony formation assays revealed that ∼80% of treated cells and their progeny were Scx- and Tnmd-positive. BM-MSCs seeded in collagen scaffolds and similarly treated with a single dose of BMP-12 also expressed high levels of Scx and Tnmd, as well as type I collagen and tenascin-c. Furthermore, when the treated BM-MSC-seeded scaffolds were implanted into surgically created tendon defects in vivo, robust formation of tendon-like tissue was observed after 21 days as evidenced by increased cell number, elongation and alignment along the tensile axis, greater matrix deposition and the elevated expression of tendon markers. These results indicate that brief stimulation with BMP-12 in vitro is sufficient to induce BM-MSC differentiation into tenocytes, and that this phenotype is sustained in vivo. This strategy of pretreating BM-MSCs with BMP-12 prior to in vivo transplantation may be useful in MSC-based tendon reconstruction or tissue engineering

Idiopathic sclerosing mesenteritis in paediatrics: Report of a successfully treated case and a review of literature

A 6 year old female with symptoms of small bowel obstruction underwent an exploratory laparotomy which revealed widespread evidence of inflammatory fibrotic adhesions involving the jejunal mesentery. In view of persistent growth failure, chronic anaemia, elevated acute phase reactants and imaging evidence of a diffuse progressive inflammatory process, the child was treated with corticosteroids and methotrexate with complete response. The literature on juvenile idiopathic sclerosing mesenteritis has been reviewed