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Introduction: Designs for determining nociceptive response in rodents are of great use in neurology and experimental neuroscience. Immersing mice's tails in warm water is one of the most widely used procedures to evaluate this response; however, a wide range of temperatures are used in different studies. Knowing the temperature that produces a powerful nociceptive response in the tail of BALB/c mice is extremely useful., Methods: Eight 2-month-old male BALB/c mice were used. A 14-cm high beaker was filled with water up to 13cm. The animals' tails were immersed in the container with a starting temperature of 36°C. The water temperature was raised in 1°C increments until we identified the temperatures that produced nociceptive responses. That response was determined by counting the time taken before the mouse shook its tail to remove it from the water., Results: Six of the 8 mice began shaking their tails at the temperature of 51°C. All animals removed their tails from the water at the temperatures of 54°C, 55°C, and 56°C, taking a mean time of 8.54, 7.99, and 5.33seconds, respectively. ANOVA applied to the response times for each of the 3 temperatures indicated revealed a value of F=2.8 (P=.123)., Conclusions: The response time was statistically similar for the temperatures of 54°C, 55°C, and 56°C; however, the data were less dispersed for the latter temperature., (Copyright © 2018 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.)

Filamentous, heterocyst-forming cyanobacteria belonging to taxonomic subsections IV and V are developmentally complex multicellular organisms capable of differentiating an array of cell and filament types, including motile hormogonia. Hormogonia exhibit gliding motility that facilitates dispersal, phototaxis, and the establishment of nitrogen-fixing symbioses. The gene regulatory network (GRN) governing hormogonium development involves a hierarchical sigma factor cascade, but the factors governing the activation of this cascade are currently undefined. Here, using a forward genetic approach, we identified hrmK , a gene encoding a putative hybrid histidine kinase that functions upstream of the sigma factor cascade. The deletion of hrmK produced nonmotile filaments that failed to display hormogonium morphology or accumulate hormogonium-specific proteins or polysaccharide. Targeted transcriptional analyses using reverse transcription-quantitative PCR (RT-qPCR) demonstrated that hormogonium-specific genes both within and outside the sigma factor cascade are drastically downregulated in the absence of hrmK and that hrmK may be subject to indirect, positive autoregulation via sigJ and sigC Orthologs of HrmK are ubiquitous among, and exclusive to, heterocyst-forming cyanobacteria. Collectively, these results indicate that hrmK functions upstream of the sigma factor cascade to initiate hormogonium development, likely by modulating the phosphorylation state of an unknown protein that may serve as the master regulator of hormogonium development in heterocyst-forming cyanobacteria. IMPORTANCE Filamentous cyanobacteria are morphologically complex, with several representative species amenable to routine genetic manipulation, making them excellent model organisms for the study of development. Furthermore, two of the developmental alternatives, nitrogen-fixing heterocysts and motile hormogonia, are essential to establish nitrogen-fixing symbioses with plant partners. These symbioses are integral to global nitrogen cycles and could be artificially recreated with crop plants to serve as biofertilizers, but to achieve this goal, detailed understanding and manipulation of the hormogonium and heterocyst gene regulatory networks may be necessary. Here, using the model organism Nostoc punctiforme , we identify a previously uncharacterized hybrid histidine kinase that is confined to heterocyst-forming cyanobacteria as the earliest known participant in hormogonium development., (Copyright © 2020 American Society for Microbiology.)

Over 80% of pancreatic ductal adenocarcinoma (PDA) patients are diagnosed with non-resectable late-stage disease that lacks effective neoadjuvant therapies. Stereotactic body radiation therapy (SBRT) has shown promise as an emerging neoadjuvant approach for treating PDA, and here, we report that its combination with local interleukin-12 (IL-12) microsphere (MS) immunotherapy results in marked tumor reduction and cures in multiple preclinical mouse models of PDA. Our findings demonstrate an increase of intratumoral interferon gamma (IFNγ) production following SBRT/IL-12 MS administration that initiates suppressor cell reprogramming and a subsequent increase in CD8 T cell activation. Furthermore, SBRT/IL-12 MS therapy results in the generation of systemic tumor immunity that is capable of eliminating established liver metastases, providing a rationale for follow-up studies in advanced metastatic disease., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Designs for determining nociceptive response in rodents are of great use in neurology and experimental neuroscience. Immersing mice's tails in warm water is one of the most widely used procedures to evaluate this response; however, a wide range of temperatures are used in different studies. Knowing the temperature that produces a powerful nociceptive response in the tail of BALB/c mice is extremely useful., Methods: Eight 2-month-old male BALB/c mice were used. A 14-cm high beaker was filled with water up to 13 cm. The animals' tails were immersed in the container with a starting temperature of 36°C. The water temperature was raised in 1°C increments until we identified the temperatures that produced nociceptive responses. That response was determined by counting the time taken before the mouse shook its tail to remove it from the water., Results: Six of the 8 mice began shaking their tails at the temperature of 51°C. All animals removed their tails from the water at the temperatures of 54°C, 55°C, and 56°C, taking a mean time of 8.54, 7.99, and 5.33seconds, respectively. ANOVA applied to the response times for each of the 3 temperatures indicated revealed a value of F=2.8 (P=.123)., Conclusions: The response time was statistically similar for the temperatures of 54°C, 55°C, and 56°C; however, the data were less dispersed for the latter temperature., (Copyright © 2018 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Although radiotherapy (RT) is widely used to control tumor growth across many cancer types, there is a relatively high incidence of RT failure exhibited by tumor recurrence, therefore a clear need exists to achieve improved effectiveness of RT. The RT-elicited immune response largely impacts the efficacy of RT and includes immune cells that kill tumor cells, but also immunosuppressive cells, which dampen anti-tumor immunity. Using murine models in which syngeneic tumor cell lines (Colon38, Glioma261, Line1) are grown intramuscularly and treated with 15 Gy local RT, we assessed the effects of RT on both the systemic and intratumoral immune response. Here we demonstrate that RT stimulates increased production of two chemokines, CCL2 and CCL5, at the tumor site. Further, that this leads to increased CCR2+ CCR5+ monocytes in circulation and subsequently alters the intratumoral immune infiltrate favoring the largely immunosuppressive CCR2+ CCR5+ monocytes. Importantly, a CCR2/CCR5 antagonist administered daily (15 mg/kg subcutaneously) starting two days prior to RT reduces both circulating and intratumoral monocytes resulting in increased efficacy of RT in radioresponsive tumors. Overall, these data have important implications for the mechanism of RT and present a means to improve RT efficacy across many cancer types.

Heterotopic ossification (HO) is a complication following total hip arthroplasty (THA) with traditional approaches. The direct anterior approach (DAA) has become a popular approach for THA; however, no study has evaluated HO formation following DAA THA. We examined the incidence of HO in a consecutive series of THA using the DAA in two separate hospitals. Standard preoperative radiographs were examined to determine the type of degenerative arthritis, and follow-up radiographs of at least 6 months after surgery were evaluated for the presence and classification of HO. The overall incidence of HO after DAA THA in this study was 98/236, or 41.5%, which falls within the reported range from recent studies involving more traditional approaches to the hip., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Despite advances in surgical techniques, 20% to 90% of rotator cuff (RTC) repairs fail. They tend to fail at the suture-tendon junction due to tension at the repair and gap formation prior to healing. This study evaluated the gap formation and ultimate tensile failure loads of a RTC repair with a decellularized human dermal allograft. Augmentation of a RTC repair with an extracellular matrix graft decreased gap formation and increased load to failure in a human RTC repair model., (Copyright 2014, SLACK Incorporated.)

Groin pain is often related to hip pathology. As a result, groin pain is a clinical complaint encountered by orthopaedic surgeons. Approximately one in four persons will develop symptomatic hip arthritis before age 85 years. Groin injuries account for approximately 1 in 20 athletic injuries, and groin pain accounts for 1 in 10 patient visits to sports medicine centers. Many athletes with chronic groin pain have multiple coexisting pathologies spanning several disciplines. In treating these patients, the orthopaedic surgeon must consider both musculoskeletal groin disorders and nonorthopaedic conditions that can present as groin pain. A comprehensive history and physical examination can guide the evaluation of groin pain.

Core decompression and placement of the Trabecular Metal Osteonecrosis Intervention Implant have shown to be initially successful in treating early osteonecrosis. When treatment fails, however, patients often undergo primary total hip arthroplasty (THA) requiring removal of a previously inserted trabecular metal implant. We describe a technical tip for removal of a well-ingrown trabecular metal screw. A metal-cutting trephine placed over the screw allows for removal in an efficient manner while minimizing additional dissection and bone loss during conversion to THA., (Copyright © 2012 Elsevier Inc. All rights reserved.)