Striking enhancement at the site of radiation for nivolumab-induced Stevens-Johnson syndrome

Stevens-Johnson syndrome is a rare adverse cutaneous drug reaction characterized by epidermal detachment of <10% body surface area with an average mortality rate of 1-5%. The mechanism of SJS is not fully understood. Nivolumab is a monoclonal antibody directed against programmed cell death-1 protein (PD-1), a receptor with immune checkpoint inhibitory and antineoplastic activities. We present a case of SJS in a patient being treated with anti-PD-1 therapy nivolumab for metastatic squamous cell carcinoma of the oropharynx. This case is unusual because of the severe accentuation with striking enhancement at his prior radiation site and in the cutaneous region with heavier tumor burden from his metastatic disease. This reaction may give insight to the underlying pathophysiology of SJS, suggesting that immune checkpoint inhibitors can activate T-cells to target keratinocytes and that external factors may be involved in creating distinct epitopes for T-cell recognition. We hope this case adds to the body of knowledge in the pathogenesis of Stevens-Johnson syndrome and cutaneous adverse events seen with checkpoint inhibitors

Pyoderma gangrenosum: a presenting sign of myelodysplastic syndrome in undiagnosed Fanconi anemia

A 26-year-old man with a history of congenital bilateral microtia, unilateral renal agenesis, left aural atresia, and right external auditory canal occlusion admitted for right rib cartilage graft harvest and left ear re-construction. Following surgery, an ulceration with violaceous borders and a yellow fibrinous base unresponsive to broad-spectrum antibiotics developed at the harvest site. The wound was expanding and not responsive to systemic broad-spectrum antibiotics. Biopsy revealed a dense dermal infiltrate of neutrophils with negative tissue cultures consistent with pyoderma gangrenosum (PG). He was treated with systemic, intralesional, and topical steroids, as well as doxycycline. Three weeks after the diagnosis of PG, he was found to have persistent anemia and leukopenia. Bone marrow aspiration analysis was consistent with hypocellular myelodysplastic syndrome and genetic testing was consistent with Fanconi anemia. There is a well-known association of PG with hematological disorders. Fanconi anemia is a rare genetic hematologic disorder with congenital defects leading to bone marrow failure and malignancy in long-standing disease. In our patient, we consider his development of PG a paraneoplastic sign associated with the onset of his hypocellular myelodysplastic syndrome

Recent advancements in nano-lubrication strategies for machining processes considering their health and environmental impacts

Industries have been seeking an efficient lubrication system that meets the requirement of sustainability without compromising manufacturing efficiency or final part quality. Conventional cutting fluids have been recognized as hazardous to the environment, health and economy of industries. The nano lubrication strategy has emerged as a sustainable and power-efficient lubrication system with encouraging performance in machining processes. This paper encapsulates an overview of the impact regarding usage of nanofluid as a cutting fluid in different machining processes. The recent innovations in the past decade, altered nano lubrication systems have been briefly summarized. A state of art review commences with a short synopsis of the historic perspective followed by a summary of the impact of nanofluid on different machining processes. The discussion section has been bifurcated according to the characterization of machining performance metrics. The environmental and health issues that emerged with the use of nanofluid are then discoursed thoroughly. Finally, the major findings are summarized and the future scope of research is identified. It can be quantified that the implementation of a nano lubrication system can significantly improve the heat transfer characteristic of base fluid which ultimately leads to the functionally tremendous product. However, there are major unknowns related to the health and environmental impact of nanoparticles

Use of natural substitutes as an intracanal medicament in the endodontics-An update for in vivo studies

165-168The success of root canal treatment depends on the elimination of bacteria by chemo-mechanical instrumentation and use of various irrigants to remove or dissolve organic and inorganic debris.The intracanal medicament also has an important role in the outcome of root canal treatment. With the rise in bacterial resistance to antibiotics, there is considerable interest in the development of other classes of antimicrobials for the control of infection. Use of Herbal intracanal medicament has been shown promising results when used under in vitro conditions, but very limited clinical trials reported due to the ethical concern. Hence, this review highlights the current guidelines (laid by the drugs and cosmetics act as per the Gazette of India) regarding the use of herbal medicaments for the clinical trials in Endodontics

Use of natural substitutes as an intracanal medicament in the endodontics-An update for in vivo studies

The success of root canal treatment depends on the elimination of bacteria by chemo-mechanical instrumentation and use of various irrigants to remove or dissolve organic and inorganic debris.The intracanal medicament also has an important role in the outcome of root canal treatment. With the rise in bacterial resistance to antibiotics, there is considerable interest in the development of other classes of antimicrobials for the control of infection. Use of Herbal intracanal medicament has been shown promising results when used under in vitro conditions, but very limited clinical trials reported due to the ethical concern. Hence, this review highlights the current guidelines (laid by the drugs and cosmetics act as per the Gazette of India) regarding the use of herbal medicaments for the clinical trials in Endodontics

Lymphangioma Circumscriptum of the Vulva- A Case Series

Vulval dermatoses pose a diagnostic and therapeutic challenge for the dermatologists. Lymphangioma Circumscriptum (LC) is a form of lymphangioma affecting the skin and subcutaneous tissues that is characterised by benign dilation of lymphatic channels. This uncommon condition is known to occur over the chest, mouth, axilla, tongue, and rarely in the vulva. In this series, authors present three cases of LC of vulva in women between the age group of 45 to 60 years with late-onset fluid-filled lesions over the vulva. The first case had history of hysterectomy prior to onset of lesions, the second case had a spontaneous onset of lesions while the third was a suspected case of pelvic tuberculosis with secondary lymphangioma

Functional and Anatomical Outcomes of Facial Nerve Injury With Application of Polyethylene Glycol in a Rat Model

Importance: Functional and anatomical outcomes after surgical repair of facial nerve injury may be improved with the addition of polyethylene glycol (PEG) to direct suture neurorrhaphy. The application of PEG has shown promise in treating spinal nerve injuries, but its efficacy has not been evaluated in treatment of cranial nerve injuries. Objective: To determine whether PEG in addition to neurorrhaphy can improve functional outcomes and synkinesis after facial nerve injury. Design, Setting, and Subjects: In this animal experiment, 36 rats underwent right facial nerve transection and neurorrhaphy with addition of PEG. Weekly behavioral scoring was done for 10 rats for 6 weeks and 14 rats for 16 weeks after the operations. In the 16-week study, the buccal branches were labeled and tissue analysis was performed. In the 6-week study, the mandibular and buccal branches were labeled and tissue analysis was performed. Histologic analysis was performed for 10 rats in a 1-week study to assess the association of PEG with axonal continuity and Wallerian degeneration. Six rats served as the uninjured control group. Data were collected from February 8, 2016, through July 10, 2017. Intervention: Polyethylene glycol applied to the facial nerve after neurorrhaphy. Main Outcomes and Measures: Functional recovery was assessed weekly for the 16- and 6-week studies, as well as motoneuron survival, amount of regrowth, specificity of regrowth, and aberrant branching. Short-term effects of PEG were assessed in the 1-week study. Results: Among the 40 male rats included in the study, PEG addition to neurorrhaphy showed no functional benefit in eye blink reflex (mean [SEM], 3.57 [0.88] weeks; 95% CI, -2.8 to 1.9 weeks; P = .70) or whisking function (mean [SEM], 4.00 [0.72] weeks; 95% CI, -3.6 to 2.4 weeks; P = .69) compared with suturing alone at 16 weeks. Motoneuron survival was not changed by PEG in the 16-week (mean, 132.1 motoneurons per tissue section; 95% CI, -21.0 to 8.4; P = .13) or 6-week (mean, 131.1 motoneurons per tissue section; 95% CI, -11.0 to 10.0; P = .06) studies. Compared with controls, neither surgical group showed differences in buccal branch regrowth at 16 (36.9 motoneurons per tissue section; 95% CI, -14.5 to 22.0; P = .28) or 6 (36.7 motoneurons per tissue section; 95% CI, -7.8 to 18.5; P = .48) weeks or in the mandibular branch at 6 weeks (25.2 motoneurons per tissue section; 95% CI, -14.5 to 15.5; P = .99). Addition of PEG had no advantage in regrowth specificity compared with suturing alone at 16 weeks (15.3% buccal branch motoneurons with misguided projections; 95% CI, -7.2% to 11.0%; P = .84). After 6 weeks, the number of motoneurons with misguided projections to the mandibular branch showed no advantage of PEG treatment compared with suturing alone (12.1% buccal branch motoneurons with misguided projections; 95% CI, -8.2% to 9.2%; P = .98). In the 1-week study, improved axonal continuity and muscular innervation were not observed in PEG-treated rats. Conclusions and Relevance: Although PEG has shown efficacy in treating other nervous system injuries, PEG in addition to neurorraphy was not beneficial in a rat model of facial nerve injury. The addition of PEG to suturing may not be warranted in the surgical repair of facial nerve injury. Level of Evidence: NA

Chikungunya Outbreak, South India, 2006

We investigated chikungunya outbreaks in South India and observed a high attack rate, particularly among adults and women. Transmission was facilitated by Aedes aegypti mosquitoes in peridomestic water containers, as indicated by a high Breteau index. We recommended vector control measures and health education to promote safe water storage practices

Development of a step-down method for altering male C57BL/6 mouse housing density and hierarchical structure: Preparations for spaceflight studies

This study was initiated as a component of a larger undertaking designed to study bone healing in microgravity aboard the International Space Station (ISS). Spaceflight experimentation introduces multiple challenges not seen in ground studies, especially with regard to physical space, limited resources, and inability to easily reproduce results. Together, these can lead to diminished statistical power and increased risk of failure. It is because of the limited space, and need for improved statistical power by increasing sample size over historical numbers, NASA studies involving mice require housing mice at densities higher than recommended in the Guide for the Care and Use of Laboratory Animals (National Research Council, 2011). All previous NASA missions in which mice were co-housed, involved female mice; however, in our spaceflight studies examining bone healing, male mice are required for optimal experimentation. Additionally, the logistics associated with spaceflight hardware and our study design necessitated variation of density and cohort make up during the experiment. This required the development of a new method to successfully co-house male mice while varying mouse density and hierarchical structure. For this experiment, male mice in an experimental housing schematic of variable density (Spaceflight Correlate) analogous to previously established NASA spaceflight studies was compared to a standard ground based housing schematic (Normal Density Controls) throughout the experimental timeline. We hypothesized that mice in the Spaceflight Correlate group would show no significant difference in activity, aggression, or stress when compared to Normal Density Controls. Activity and aggression were assessed using a novel activity scoring system (based on prior literature, validated in-house) and stress was assessed via body weights, organ weights, and veterinary assessment. No significant differences were detected between the Spaceflight Correlate group and the Normal Density Controls in activity, aggression, body weight, or organ weight, which was confirmed by veterinary assessments. Completion of this study allowed for clearance by NASA of our bone healing experiments aboard the ISS, and our experiment was successfully launched February 19, 2017 on SpaceX CRS-10

Impact of peripheral immune status on central molecular responses to facial nerve axotomy

When facial nerve axotomy (FNA) is performed on immunodeficient recombinase activating gene-2 knockout (RAG-2-/-) mice, there is greater facial motoneuron (FMN) death relative to wild type (WT) mice. Reconstituting RAG-2-/- mice with whole splenocytes rescues FMN survival after FNA, and CD4+ T cells specifically drive immune-mediated neuroprotection. Evidence suggests that immunodysregulation may contribute to motoneuron death in amyotrophic lateral sclerosis (ALS). Immunoreconstitution of RAG-2-/- mice with lymphocytes from the mutant superoxide dismutase (mSOD1) mouse model of ALS revealed that the mSOD1 whole splenocyte environment suppresses mSOD1 CD4+ T cell-mediated neuroprotection after FNA. The objective of the current study was to characterize the effect of CD4+ T cells on the central molecular response to FNA and then identify if mSOD1 whole splenocytes blocked these regulatory pathways. Gene expression profiles of the axotomized facial motor nucleus were assessed from RAG-2-/- mice immunoreconstituted with either CD4+ T cells or whole splenocytes from WT or mSOD1 donors. The findings indicate that immunodeficient mice have suppressed glial activation after axotomy, and cell transfer of WT CD4+ T cells rescues microenvironment responses. Additionally, mSOD1 whole splenocyte recipients exhibit an increased astrocyte activation response to FNA. In RAG-2-/- + mSOD1 whole splenocyte mice, an elevation of motoneuron-specific Fas cell death pathways is also observed. Altogether, these findings suggest that mSOD1 whole splenocytes do not suppress mSOD1 CD4+ T cell regulation of the microenvironment, and instead, mSOD1 whole splenocytes may promote motoneuron death by either promoting a neurotoxic astrocyte phenotype or inducing Fas-mediated cell death pathways. This study demonstrates that peripheral immune status significantly affects central responses to nerve injury. Future studies will elucidate the mechanisms by which mSOD1 whole splenocytes promote cell death and if inhibiting this mechanism can preserve motoneuron survival in injury and disease