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Antiphospholipid syndrome (APS) is an acquired autoimmune clinical disorder characterized by persistently raised levels of anti-phospholipid antibodies and clinical feature of hypercoagulability (recurrent vascular thrombosis and pregnancy morbidities). Primary APS is idiopathic in nature though secondary APS is associated with other connective tissue diseases like SLE. Here, we present an instance of primary APS with recurrent cerebral venous sinus thrombosis in a youthful unmarried female who clinically presented with generalized epilepsy. Level of anti-cardiolipin (aCL) and anti-beta 2 GP1 antibodies were found elevated on two occasions 12 weeks apart. The patient was treated with anticoagulation therapy along with anti-epileptic therapy and she responded well to the therapy. This case report highlights that clinicians should always suspect APS in female patients who had history of seizures and ischemic or thrombotic lesions on brain imaging, irrespective of presence of pregnancy comorbidities.

Background: Metabolic syndrome and diabetes in obese individuals are strong risk factors for development of inflammatory bowel disease (IBD) and colorectal cancer. The pathogenic mechanisms of low-grade metabolic inflammation, including chronic hyperglycemic stress, in disrupting gut homeostasis are poorly understood. In this study, we sought to understand the impact of a hyperglycemic environment on intestinal barrier integrity and the protective effects of small molecular weight (35 kDa) hyaluronan on epithelial barrier function., Methods: Intestinal organoids derived from mouse colon were grown in normal glucose media (5 mM) or high glucose media (25 mM) to study the impact of hyperglycemic stress on the intestinal barrier. Additionally, organoids were pretreated with 35 kDa hyaluronan (HA35) to investigate the effect of hyaluronan on epithelial barrier under high glucose stress. Immunoblotting as well as confocal imaging was used to understand changes in barrier proteins, quantitative as well as spatial distribution, respectively. Alterations in barrier function were measured using trans-epithelial electrical resistance and fluorescein isothiocyanate flux assays. Untargeted proteomics analysis was performed to elucidate mechanisms by which HA35 exerts a protective effect on the barrier. Intestinal organoids derived from receptor knockout mice specific to various HA receptors were utilized to understand the role of HA receptors in barrier protection under high glucose conditions., Results: We found that high glucose stress decreased the protein expression as well as spatial distribution of two key barrier proteins, zona occludens-1 (ZO-1) and occludin. HA35 prevented the degradation or loss of ZO-1 and maintained the spatial distribution of both ZO-1 and occludin under hyperglycemic stress. Functionally, we also observed a protective effect of HA35 on the epithelial barrier under high glucose conditions. We found that HA receptor, layilin, was involved in preventing barrier protein loss (ZO-1) as well as maintaining spatial distribution of ZO-1 and occludin. Additionally, proteomics analysis showed that cell death and survival was the primary pathway upregulated in organoids treated with HA35 under high glucose stress. We found that XIAP associated factor 1 (Xaf1) was modulated by HA35 thereby regulating apoptotic cell death in the intestinal organoid system. Finally, we observed that spatial organization of both focal adhesion kinase (FAK) as well as F-actin was mediated by HA35 via layilin., Conclusion: Our results highlight the impact of hyperglycemic stress on the intestinal barrier function. This is of clinical relevance, as impaired barrier function has been observed in individuals with metabolic syndrome. Additionally, we demonstrate barrier protective effects of HA35 through its receptor layilin and modulation of cellular apoptosis under high glucose stress., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background : The adoption of robotic bariatric surgery has increased dramatically over the last decade. While outcomes comparing bariatric and laparoscopic approaches are debated, little is known about patient factors responsible for the growing delivery of robotic surgery. A better understanding of these factors will help guide the planning of bariatric delivery and resource allocation. Methods : Data were extracted from the MBSAQIP registry from 2020 to 2021. The patient population was organized into primary robot-assisted sleeve gastrectomy or Roux-en-Y gastric bypass (RYGB) versus those who underwent laparoscopic procedures. Bivariate analysis and multivariable logistic regression modeling were conducted to characterize cohort differences and identify independent patient predictors of robotic selection. Results : Of 318,151, 65,951 (20.7%) underwent robot-assisted surgery. Patients undergoing robotic procedures were older (43.4 ± 11.8 vs. 43.1 ± 11.8; p < 0.001) and had higher body mass index (BMI; 45.4 ± 7.9 vs. 45.0 ± 7.6; p < 0.001). Robotic cases had higher rates of medical comorbidities, including sleep apnea, hyperlipidemia, gastroesophageal reflux disease (GERD), and diabetes mellitus. Robotic cases were more likely to undergo RYGB (27.4% vs. 26.4%; p < 0.001). Robotic patients had higher rates of numerous complications, including bleed, reoperation, and reintervention, resulting in higher serious complication rates on multivariate analysis. Independent predictors of robotic selection included increased BMI (aOR 1.02), female sex (aOR 1.04), GERD (aOR 1.12), metabolic dysfunction, RYGB (aOR 1.08), black racial status (aOR 1.11), and lower albumin (aOR 0.84). Conclusions : After adjusting for comorbidities, patients with greater metabolic comorbidities, black racial status, and those undergoing RYGB were more likely to receive robotic surgery. A more comprehensive understanding of patient factors fueling the adoption of robotic delivery, as well as those expected to benefit most, is needed to better guide healthcare resources as the landscape of bariatric surgery continues to evolve.

Purpose: New treatments are needed to improve the overall survival of patients with glioblastoma Metformin is known for anti-tumorigenic effects in cancers, including breast and pancreas cancers. In this study, we assessed the association between metformin use and overall survival in glioblastoma patients., Methods: We retrospectively studied 241 patients who underwent surgery at diagnosis of glioblastoma between 2014 and 2018. Metformin was used for pre-existing type 2 diabetes mellitus or in the prevention or management of glucocorticoid induced hyperglycemia. Kaplan-Meier curves and log-rank p test were used for univariate analysis. Cox-proportional hazards model was used to generate adjusted hazard ratios for multivariate analysis., Results: Metformin use was associated with longer survival in patients with tumors that had a methylated O6-methylguanine DNA methyltransferase gene (MGMT) promoter (484 days 95% CI: 56-911 vs. 394 days 95% CI: 249-538, Log-Rank test: 6.5, p = 0.01). Cox regression analysis shows that metformin associates with lower risk of death at 2 years in patients with glioblastoma containing a methylated MGMT promoter (aHR = 0.497, 95% CI 0.26-0.93, p = 0.028)., Conclusion: Our findings suggest a survival benefit with metformin use in patients with glioblastomas having methylation of the MGMT promoter., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Pyoderma gangrenosum (PG) is a debilitating skin condition often accompanied by inflammatory bowel disease (IBD). Strikingly, ~40% of patients that present with PG have underlying IBD, suggesting shared but unknown mechanisms of pathogenesis. Impeding the development of effective treatments for PG is the absence of an animal model that exhibits features of both skin and gut manifestations. This study describes the development of the first experimental drug-induced mouse model of PG with concomitant intestinal inflammation. Topical application of pyrimidine synthesis inhibitors on wounded mouse skin generates skin ulcers enriched in neutrophil extracellular traps (NETs) as well as pro-inflammatory cellular and soluble mediators mimicking human PG. The mice also develop spontaneous intestinal inflammation demonstrated by histologic damage. Further investigations revealed increased circulating low density IL-1β primed neutrophils that undergo enhanced NETosis at inflamed tissue sites supported by an increase in circulatory citrullinated histone 3, a marker of aberrant NET formation. Granulocyte depletion dampens the intestinal inflammation in this model, further supporting the notion that granulocytes contribute to the skin-gut crosstalk in PG mice. We anticipate that this novel murine PG model will enable researchers to probe common disease mechanisms and identify more effective targets for treatment for PG patients with IBD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jatana, Ponti, Johnson, Rebert, Smith, Fulmer, Maytin, Achkar, Fernandez and McDonald.)

Introduction: Patients undergoing bariatric surgery experience substantial risk of pre- and postoperative substance use. Identifying patients at risk for substance use using validated screening tools remains crucial to risk mitigation and operative planning. We aimed to evaluate proportion of bariatric surgery patients undergoing specific substance abuse screening, factors associated with screening and the relationship between screening and postoperative complications., Methods: The 2021 MBSAQIP database was analyzed. Bivariate analysis was performed to compare factors between groups who were screened for substance abuse versus non-screened, and to compare frequency of outcomes. Multivariate logistic regression analysis was performed to assess the independent effect of substance screening on serious complications and mortality, and to assess factors associated with substance abuse screening., Results: A total of 210, 804 patients were included, with 133,313 (63.2%) undergoing screening and 77,491 (36.8%) who did not. Those who underwent screening were more likely to be white, non-smoker, and have more comorbidities. The frequency of complications was not significant (e.g., reintervention, reoperation, leak) or similar (readmission rates 3.3% vs. 3.5%) between screened and not screened groups. On multivariate analysis, lower substance abuse screening was not associated with 30-day death or 30-day serious complication. Factors that significantly affected likelihood of being screened for substance abuse included being black (aOR 0.87, p < 0.001) or other race (aOR 0.82, p < 0.001) compared to white, being a smoker (aOR 0.93, p < 0.001), having a conversion or revision procedure (aOR 0.78, p < 0.001; aOR 0.64, p < 0.001, respectively), having more comorbidities and undergoing Roux-en-y gastric bypass (aOR 1.13, p < 0.001)., Conclusion: There remains significant inequities in substance abuse screening in bariatric surgery patients regarding demographic, clinical, and operative factors. These factors include race, smoking status, presence of preoperative comorbidities, and procedure type. Further awareness and initiatives highlighting the importance of identifying at risk patients is critical for ongoing outcome improvement., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: It is important to appropriately risk stratify bariatric surgery patients, as these patients often have obesity-related comorbidities which can increase postoperative complication risk but also benefit the most from bariatric surgery. We aimed to evaluate the utility of risk stratification using ASA class for bariatric surgery patients and assessed predictive factors of postoperative complications., Methods: The 2020 MBSAQIP database was analyzed, and an ASA-deemed high-risk cohort (class IV) and normal-risk (ASA class II and III) cohort were compared. Univariate analysis was performed to characterize differences between cohorts and to compare complication rates. Multivariate logistic regression analysis was performed to determine factors associated with increased odds of postoperative complications., Results: We evaluated 138 612 patients with 5380 (3.9%) considered high-risk and 133 232 (96.1%) normal-risk. High-risk patients were more likely to be older (46.2 ± 12.0vs.43.4 ± 11.9, p < 0.001), male (30.9%vs.18.4%, p < 0.001), have higher BMI (51.4 ± 10.2vs.44.9 ± 7.4, p < 0.001), and have more comorbidities. High-risk patients were more likely to have increased 30-day serious complications (4.5%vs.2.8%, p < 0.001) and death (0.2%vs.0.1%, p = 0.001) but not anastomotic leak (0.2%vs.0.2%, p = 0.983). Multivariate models showed ASA class IV patients were at higher odds for any serious complication by 30 days (aOR 1.36, 95%CI 1.18-1.56, p < 0.001) but not for death (aOR 1.04, 95%CI 0.49-2.21, p = 0.921). The factor independently associated with the highest odds of complication in both models was functional status preoperatively (partially dependent aOR 2.06, 95%CI 1.56-2.72, p < 0.001; fully dependent aOR 3.19, 95%CI 1.10-9.28, p = 0.033 for any serious complication; partially dependent aOR 5.08, 95%CI 2.16-12.00, p < 0.001 for death)., Conclusions: While elevated ASA class correlates with increased serious complications, pre-operative functional status appears to have a much greater contribution to odds of serious complications and mortality. These findings question the utility of using ASA to risk stratify patients peri-operatively and provides evidence for using a simpler and more practical functional status approach., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Postoperative morbidity in glioblastoma (GBM) patients can be due to the disease course but can also come from postoperative complications. Our objective was to study the association of dexamethasone use and perioperative hyperglycemia with postoperative complications in GBM patients., Methods: A single-center, retrospective cohort study was conducted in patients who underwent surgery for primary GBM from 2014-2018. Patients with perioperative fasting blood glucose (FBG) measurements and adequate follow-up to assess for complications were included., Results: A total of 199 patients were included. More than half (53%) had poor perioperative glycemic control (FBG ≥ 7 mM for ≥ 20% perioperative days). Higher dexamethasone dose (≥ 8 mg) was associated with higher FBG on postoperative days 2-4 and 5 (p = 0.02,0.05,0.004,0.02, respectively). Poor glycemic control was associated with increased odds of 30-day any complication and 30-day infection on univariate analysis (UVA), and 30-day any complication and increased length of stay (LOS) on multivariate analysis (MVA). Higher average perioperative daily dexamethasone dose was associated with increased odds of 30-day any complication and 30-day infection on MVA. Elevated hemoglobin A1c (HgbA1c, ≥ 6.5%) was associated with increased odds of 30-day any complication, 30-day infection, and LOS on UVA. In a multivariate linear regression model, only the diagnosis of diabetes mellitus predicted perioperative hyperglycemia., Conclusions: Perioperative hyperglycemia, higher average dexamethasone use and elevated preoperative HgbA1c are associated with increased risk of postoperative complications in GBM patients. Avoiding hyperglycemia and limiting dexamethasone use in postoperative period may decrease the risk of complications. Select HgbA1c screening may allow the identification of a group of patients at higher risk of complications., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Hospitalized patients have an increased risk of developing hospital-acquired sacral pressure injury (HASPI). However, it is unknown whether SARS-CoV-2 infection affects HASPI development. To explore the role of SARS-CoV-2 infection in HASPI development, we conducted a single institution, multi-hospital, retrospective study of all patients hospitalized for ≥5 days from March 1, 2020 to December 31, 2020. Patient demographics, hospitalization information, ulcer characteristics, and 30-day-related morbidity were collected for all patients with HASPIs, and intact skin was collected from HASPI borders in a patient subset. We determined the incidence, disease course, and short-term morbidity of HASPIs in COVID-19(+) patients, and characterized the skin histopathology and tissue gene signatures associated with HASPIs in COVID-19 disease. COVID-19(+) patients had a 63% increased HASPI incidence rate, HASPIs of more severe ulcer stage (OR 2.0, p<0.001), and HASPIs more likely to require debridement (OR 3.1, p=0.04) compared to COVID-19(-) patients. Furthermore, COVID-19(+) patients with HASPIs had 2.2x increased odds of a more severe hospitalization course compared to COVID-19(+) patients without HASPIs. HASPI skin histology from COVID-19(+) patients predominantly showed thrombotic vasculopathy, with the number of thrombosed vessels being significantly greater than HASPIs from COVID-19(-) patients. Transcriptional signatures of a COVID-19(+) sample subset were enriched for innate immune responses, thrombosis, and neutrophil activation genes. Overall, our results suggest that immunologic dysregulation secondary to SARS-CoV-2 infection, including neutrophil dysfunction and abnormal thrombosis, may play a pathogenic role in development of HASPIs in patients with severe COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Narang, Jatana, Ponti, Musich, Gallop, Wei, Seck, Johnson, Kokoczka, Nowacki, McBride, Mireles-Cabodevila, Gordon, Cooper, Fernandez and McDonald.)

Background: There is uncertainty whether benign breast papillomas without atypia (BP) can be followed by imaging or require surgical resection., Methods: A single-center, retrospective cohort study of patients diagnosed with BP (2011-2021) to determine the upgrade rate on surgery, and factors associated with surgical intervention and upgrade., Results: 139 BPs were included. 27(19.4%) had upfront surgery; 112(80.6%) had imaging follow-up. The upfront surgery group had higher rates of pre-excision nipple inversion (n = 2(8.3%)vs.n = 0(0%),p = 0.003). In the imaging group, the median follow-up was 3.8years, and 9 had subsequent resection. Upgrade rate was 5.8%(8/139). Of all BPs undergoing surgery (n = 36), patients ≥60years (75.0%vs.25.0%,p = 0.049) or with family history of breast cancer (87.5%vs.48.1%,p = 0.048) were more likely to have upgrade., Conclusions: Despite a low number of events, this study supports radiologic follow-up of BP except in patients ≥60 years or with family history of breast cancer, adding to the growing body of evidence supporting watchful waiting of BPs., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Respiratory viruses pose an important public health threat to most communities. Nonpharmaceutical interventions (NPIs) such as masks, hand hygiene or physical distancing, among others, are believed to play an important role in reducing transmission of respiratory viruses. In this umbrella review, we summarise the evidence of the effectiveness of NPIs for the prevention of respiratory virus transmission in the community setting., Observations: A systematic search of PubMed, Embase, Medline and Cochrane reviews resulted in a total of 24 studies consisting of 11 systematic reviews and meta-analyses, 12 systematic reviews without meta-analyses and one standalone meta-analysis. The current evidence from these data suggests that hand hygiene is protective against respiratory viral infection. The use of hand hygiene and facemasks, facemasks alone and physical distancing were interventions with inconsistent evidence. Interventions such as school closures, oral hygiene or nasal saline rinses were shown to be effective in reducing the risk of influenza; however, the evidence is sparse and mostly of low and critically low quality., Conclusions: Studies on the effectiveness of NPIs for the prevention of respiratory viral transmission in the community vary in study design, quality and reported effectiveness. Evidence for the use of hand hygiene or facemasks is the strongest; therefore, the most reasonable suggestion is to use hand hygiene and facemasks in the community setting., Competing Interests: Conflict of interest: There is no conflict of interest to report., (Copyright ©The authors 2022.)

Severe burns are traumatic and physically debilitating injuries with a high rate of mortality. Bacterial infections often complicate burn injuries, which presents unique challenges for wound management and improved patient outcomes. Currently, pigs are used as the gold standard of pre-clinical models to study infected skin wounds due to the similarity between porcine and human skin in terms of structure and immunological response. However, utilizing this large animal model for wound infection studies can be technically challenging and create issues with data reproducibility. We present a detailed protocol for a porcine model of infected burn wounds based on our experience in creating and evaluating full thickness burn wounds infected with Staphylococcus aureus on six pigs. Wound healing kinetics and bacterial clearance were measured over a period of 27 d in this model. Enumerated are steps to achieve standardized wound creation, bacterial inoculation, and dressing techniques. Systematic evaluation of wound healing and bacterial colonization of the wound bed is also described. Finally, advice on animal housing considerations, efficient bacterial plating procedures, and overcoming common technical challenges is provided. This protocol aims to provide investigators with a step-by-step guide to execute a technically challenging porcine wound infection model in a reproducible manner. Accordingly, this would allow for the design and evaluation of more effective burn infection therapies leading to better strategies for patient care., (© 2013-2022 The Journal of Biological Methods, All rights reserved.)

Thread size and polymer composition are critical properties to consider for achieving a positive healing outcome with a wound dressing. Three-dimensional (3D) printed scaffolds and electrospun mats both offer distinct advantages as replaceable wound dressings. This research aims to determine if the thread size and polymer compositions of the scaffolds affect skin wound healing outcomes, an aspect that has not been adequately explored. Using a modular polymer platform, four polyester direct-write 3D printed scaffolds and electrospun mats were fabricated into wound dressings. The dressings were applied to splinted, full thickness skin wounds in an excisional wound rat model and evaluated against control wounds to which no dressing was applied. Wound closure rates and reduction of the wound bed width were not affected by the thread size or polymer composition. However, epidermal thickness was larger in wounds treated with electrospun dressings and was slightly affected by the polymer composition. Two of the four tested polymer compositions lead to delayed reorganization of granulation tissues. Moreover, enhanced angiogenesis was seen in wounds treated with 3D printed dressings compared to those treated with electrospun dressings. The results from this study can be used to inform the choice of dressing architecture and polymer compositions to achieve positive wound healing outcomes.

Amorphous silicon dioxide nanoparticles (SiNPs) are ubiquitous, and they are currently found in cosmetics, drugs, and foods. Biomedical research is also focused on using these nanoparticles as drug delivery and bio-sensing platforms. Due to the high potential for skin exposure to SiNPs, research into the effect of topical exposure on both healthy and inflammatory skin models is warranted. While we observe only minimal effects of SiNPs on healthy mouse skin, there is an immunomodulatory effect of these NPs in a model of allergic contact dermatitis. The effect appears to be mediated partly by keratinocytes and results in decreases in epidermal hyperplasia, inflammatory cytokine release, immune cell infiltration, and a subsequent reduction in skin swelling. Additional research is required to further our mechanistic understanding and to validate the extent of this immunomodulatory effect in human subjects in order to assess the potential prophylactic use of SiNPs for treating allergic skin conditions.

Cancer immunotherapy aimed at boosting cancer-specific immunoresponses to eradicate tumor cells has evolved as a new treatment modality. Nanoparticles incorporating antigens and immunomodulatory agents can activate immune cells and modulate the tumor microenvironment to enhance anti-tumor immunity. The nanotechnology approach has been demonstrated to be superior to standard formulations in in-vivo settings. In this article, we focus on recent advances made within the last 5 years in nanoparticle-based cancer immunotherapy, including peptide- and nucleic acid-based nanovaccines, nanomedicines containing an immunoadjuvant to activate anti-tumor immunity, nanoparticle delivery of immune checkpoint inhibitors and the combination of the above approaches. Encouraging results and new emerging nanotechnologies in drug delivery promise the continuous growth of this field and ultimately clinical translation of enhanced immunotherapy of cancer., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Iron deficiency anemia (IDA) in cyanotic congenital heart disease (CCHD) and its association with cyanotic spells has been documented in literature. However, Indian data especially in the pediatric age group is scarce. This study was conducted to find out the prevalence of IDA in this population., Methods: An observational study was conducted in a tertiary care hospital. Children with CCHD in the age group of birth-12 years were included in the study. Hematological parameters of these patients were determined and compared. An assessment of the incidence of cyanotic spells in the iron-deficient and iron non-deficient children was also done. Data analysis was done using Fischer's exact test., Results: The prevalence of IDA was 47.06% in the study population. The study also showed that hemoglobin and hematocrit levels were paradoxically higher in the iron-deficient group as compared to the non-deficient, though the iron studies revealed the iron deficiency. The incidence of cyanotic spells was higher in the iron-deficient group. The mean corpuscular volume (MCV), red cell distribution width (RDW), serum ferritin, serum iron, total iron binding capacity (TIBC), and transferrin saturation (TS) values were the parameters, which were found to be statistically significant to differentiate the study groups., Conclusion: The prevalence of IDA in children with CCHD was found to be high. Iron-deficient group had an increased frequency of cyanotic spells as compared to the non-deficient group, which was statistically significant.

Multidrug-resistant bacterial strains are a rapidly emerging healthcare threat; therefore it is critical to develop new therapies to combat these organisms. Prior antibacterial strategies directly target pathogen growth or viability. Host-directed strategies to increase antimicrobial defenses may be an effective alternative to antibiotics and reduce development of resistant strains. In this study, we demonstrated the efficacy of a pyrimidine synthesis inhibitor, N-phosphonacetyl-L-aspartate (PALA), to enhance clearance of methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and Acinetobacter baumannii strains by primary human dermal fibroblasts in vitro. PALA did not have a direct bactericidal effect, but enhanced cellular secretion of the antimicrobial peptides human β-defensin 2 (HBD2) and HBD3 from fibroblasts. When tested in porcine and human skin explant models, a topical PALA formulation was efficacious to enhance MRSA, P. aeruginosa, and A. baumannii clearance. Topical PALA treatment of human skin explants also resulted in increased HBD2 and cathelicidin (LL-37) production. The antimicrobial actions of PALA required expression of nucleotide-binding, oligomerization domain 2 (NOD2), receptor-interacting serine/threonine-protein kinase 2 (RIP2), and carbamoyl phosphatase synthase II/aspartate transcarbamylase/dihydroorotase (CAD). Our results indicate that PALA may be a new option to combat multidrug-resistant bacterial infections of the skin through enhancement of an integral pathway of the cutaneous innate immune defense system.

In recent years there has been considerable effort to understand the interaction of nanomaterials with the skin. In this study we use an in vivo mouse model of allergic contact dermatitis to investigate how nanoparticles (NPs) may alter allergic responses in skin. We investigate a variety of NPs that vary in size, charge and composition. Results show that small (<200 nm) negative and neutral charged NPs exhibit an immunosuppressive effect but that positively charged NPs do not. Confocal imaging suggests positively charged NPs may penetrate skin to a lesser extent and thereby are less able interact with and alter the local immune responses. Interestingly, negatively charged silica (20 nm) NPs suppress allergic response to two chemically distinct sensitizers; 1-fluoro-2, 4-dinitrobenzene and 2-deoxyurushiol. Skin wiping and NP application time studies suggest that the immunomodulatory mechanism is not due solely to the blocking of sensitizer adduct formation in skin. Results suggest that NPs modulate early immune events that impact mast cell degranulation. Our study shows for the first time the potential to modulate the elicitation phase of the allergic response which depends on the NP charge and composition. These finding can be used to inform the design topical therapeutics to mitigate allergic responses in skin.

Background: Previous work has demonstrated size, surface charge and skin barrier dependent penetration of nanoparticles into the viable layers of mouse skin. The goal of this work was to characterize the tissue distribution and mechanism of transport of nanoparticles beyond skin, with and without Ultraviolet Radiation (UVR) induced skin barrier disruption. Atomic absorption spectroscopy (AAS), flow cytometry and confocal microscopy were used to examine the effect of UVR dose (180 and 360 mJ/cm 2 UVB) on the skin penetration and systemic distribution of quantum dot (QD) nanoparticles topically applied at different time-points post UVR using a hairless C57BL/6 mouse model., Results: Results indicate that QDs can penetrate mouse skin, regardless of UVR exposure, as evidenced by the increased cadmium in the local lymph nodes of all QD treated mice. The average % recovery for all treatment groups was 69.68% with ~66.84% of the applied dose recovered from the skin (both epicutaneous and intracutaneous). An average of 0.024% of the applied dose was recovered from the lymph nodes across various treatment groups. When QDs are applied 4 days post UV irradiation, at the peak of the skin barrier defect and LC migration to the local lymph node, there is an increased cellular presence of QD in the lymph node; however, AAS analysis of local lymph nodes display no difference in cadmium levels due to UVR treatment., Conclusions: Our data suggests that Langerhans cells (LCs) can engulf QDs in skin, but transport to the lymph node may occur by both cellular (dendritic and macrophage) and non-cellular mechanisms. It is interesting that these specific nanoparticles were retained in skin similarly regardless of UVR barrier disruption, but the observed skin immune cell interaction with nanoparticles suggest a potential for immunomodulation, which we are currently examining in a murine model of skin allergy.

Understanding the interactions of nanoparticles (NPs) with skin is important from a consumer and occupational health and safety perspective, as well as for the design of effective NP-based transdermal therapeutics. Despite intense efforts to elucidate the conditions that permit NP penetration, there remains a lack of translatable results from animal models to human skin. The objectives of this study are to investigate the impact of common skin lotions on NP penetration and to quantify penetration differences of quantum dot (QD) NPs between freshly excised human and mouse skin. QDs were mixed in 7 different vehicles, including 5 commercial skin lotions. These were topically applied to skin using two exposure methods; a petri dish protocol and a Franz diffusion cell protocol. QD presence in the skin was quantified using Confocal Laser Scanning Microscopy. Results show that the commercial vehicles can significantly impact QD penetration in both mouse and human skin. Lotions that contain alpha hydroxyl acids (AHA) facilitated NP penetration. Lower QD signal was observed in skin studied using a Franz cell. Freshly excised human skin was also studied immediately after the sub-cutaneous fat removal process, then after 24 hours rest ex vivo . Resting human skin 24 hours prior to QD exposure significantly reduced epidermal presence. This study exemplifies how application vehicles, skin processing and the exposure protocol can affect QD penetration results and the conclusions that maybe drawn between skin models.

The study of engineered nanomaterials for the development of technological applications, nanomedicine, and nano-enabled consumer products is an ever-expanding discipline as is the concern over the impact of nanotechnology on human environmental health and safety. In this review, we discuss the current state of understanding of nanomaterial skin interactions with a specific emphasis on the effects of ultraviolet radiation (UVR) skin exposure. Skin is the largest organ of the body and is typically exposed to UVR on a daily basis. This necessitates the need to understand how UVR skin exposure can influence nanomaterial skin penetration, alter nanomaterial systemic trafficking, toxicity, and skin immune function. We explore the unique dichotomy that UVR has on inducing both deleterious and therapeutic effects in skin. The subject matter covered in this review is broadly informative and will raise awareness of potential increased risks from nanomaterial skin exposure associated with specific occupational and life style choices. The UVR-induced immunosuppressive response in skin raises intriguing questions that motivate future research directions in the nanotoxicology and nanomedicine fields., (© 2013 Wiley Periodicals, Inc.)

Ultraviolet radiation (UVR) skin exposure is a common exogenous insult that can alter skin barrier and immune functions. With the growing presence of nanoparticles (NPs) in consumer goods and technological applications the potential for NPs to contact UVR-exposed skin is increasing. Therefore it is important to understand the effect of UVR on NP skin penetration and the potential for systemic translocation. Previous studies qualitatively showed that UVR skin exposure can increase the penetration of NPs below the stratum corneum. In this work, an in vivo mouse model was used to quantitatively examine the skin penetration of carboxylated (CdSe/ZnS, core/shell) quantum dots (QDs) through intact and UVR barrier-disrupted murine skin by organ Cd mass analysis. Transepidermal water loss was used to measure the magnitude of the skin barrier defect as a function of UVR dose and time post-UVR exposure. QDs were applied to mice 3-4 days post-UVR exposure at the peak of the skin barrier disruption. Our results reveal unexpected trends that suggest these negative-charged QDs can penetrate barrier intact skin and that penetration and systemic transport depends on the QD application time post-UVR exposure. The effect of UVR on skin-resident dendritic cells and their role in the systemic translocation of these QDs are described. Our results suggest that NP skin penetration and translocation may depend on the specific barrier insult and the inflammatory status of the skin.

Background Context: Bone morphogenetic protein-2 (BMP-2) (Infuse) has been approved for use in anterior lumbar fusion in conjunction with an LT cage. However, off-label use is seen with anterior cervical fusion, posterior lumbar interbody fusion (PLIF), and transforaminal lumbar interbody fusion (TLIF). The Federal Food and Drug Administration trial of BMP-2 in a PLIF application was halted because of a high incidence of ectopic bone forming in the neural canal (75%). The authors did not find a correlation between ectopic bone and increased leg pain. They concluded that the ectopic bone was a radiographic phenomenon and not associated with clinical findings. Complications using BMP in the cervical spine have been reported. Heretofore, there has not been a similar warning voiced for use of BMP in a lumbar PLIF or TLIF., Purpose: The purpose was to report five cases of ectopic bone in the canal associated with PLIF/TLIF off-label use of BMP-2 potentially contributing to abnormal neurologic findings., Study Design/setting: This is an observational cohort study of patients referred to a tertiary care private medical center., Methods: This was a retrospective chart review of patients referred to a tertiary spine institute with complications after surgery where BMP-2 had been used in an off-label PLIF or TLIF application. Patient demographics, operating room (OR) notes from the index BMP surgery, imaging studies, and current clinical status were reviewed., Results: Five cases of ectopic bone in the spinal canal with potential neurologic compromise were identified., Conclusions: It does appear that ectopic bone in the spinal canal associated with BMP-2 use in PLIF or TLIF may contribute to symptomatic neurologic findings in rare cases. Revision surgeries are difficult. This article challenges a previous publication, which concluded that the high incidence of ectopic bone was of no clinical significance. Isolating BMP anteriorly in the disc space using layered barriers of bone graft between the BMP and the annular defect may reduce the incidence of ectopic bone in the spinal canal. Surgeons need to weigh the benefits versus risks of any technology used off label when making treatment decisions with their patients.

Background: A study was conducted to evaluate a system of standardizing the oxygen concentration inside the oxygen hood and to develop guidelines for controlled FiO2 administration by changing size of the hood, lid position on the hood and the oxygen flow rate, without an oxygen analyzer. The effect of low flow rates on carbon dioxide (CO2) retention was also studied., Method: A dummy patient and thirty neonates, requiring oxygen to be delivered through head box, constituted the material for the study group. Oxygen content in the head box was measured using a standard oxygen analyzer while the size of head box, flow rate and lid position were changed independently and in combination. The head boxes were tested on a dummy patient. These results were analyzed, and applied to thirty neonates requiring oxygen therapy using a head box., Result: Volume of headbox had an inverse relation with the oxygen concentration inside the headbox and smaller sized headbox achieved more predictable oxygen concentration at all flow rates. Maximum difference in oxygen concentration by varying the lid position was seen in the large headbox. Keeping the variables constant, oxygen concentration was significantly lower in babies as compared to dummy. No significant CO2 retention was found at a flow rate of four litres per minute (lpm) in small and three lpm in a medium and large head box respectively, while lower flow rates were associated with CO2 retention., Conclusion: It is possible to predict the oxygen concentration inside the head box without the use of oxygen analyzer. Larger head box and higher lid position, results in lower oxygen concentration, at a given oxygen flow rate. Oxygen concentration achieved in babies is lesser than the concentration achieved in a dummy. Flow rates of less than four lpm in small and three lpm in medium and large sized head boxes are associated with CO2 retention. These results are not applicable to infants weighing less than 2 kg.

Infections are still a leading cause of morbidity and mortality in children under five years of age, most of which can be prevented by vaccination. However, there are too many vaccines to be administered, increasing the cost of immunization and visits to the paediatrician. Combination vaccines can be an answer to these problems till the development of a single vaccine containing all the possible antigens. Researchers are aiming at development of an ideal vaccine, which can be given orally at birth, has negligible side effects, is heat stable and is affordable to all the parents.

Background Context: The role of total disc arthroplasty (TDA) in the treatment of spinal pathology is unclear. TDA has been touted as an alternative to fusion. However, not all back pain is purely discogenic in origin. Contraindications to TDA exist. At Spine Week in Porto, Portugal, Cammisa's group from the Hospital for Special Surgery in New York presented a series of 56 fusions where 100% of patients had one or more of 10 contraindications to TDA. En face, this appears to be an extremely large number., Purpose: The purpose of the study was to repeat the Hospital for Special Surgery study in another cohort of fusion patients., Study Design/setting: This study was an independent, retrospective record review of 100 consecutive lumbar spinal fusions performed at a tertiary care private medical center., Patient Sample: All adult patients having primary1-3 level lumbar spinal fusions from January 2003 to May 2004 were assessed., Outcome Measures: Physiologic measures included imaging, range of motion, and response to facet blocks., Methods: A retrospective chart review was performed of 100 consecutive patients having primary 1-3 level lumbar fusion by all five active staff spinal surgeons (3 orthopedic and 2 neurosurgeons). The review was performed independently by the doctorate level physiotherapist who serves as the medical center's research coordinator, reporting to the chairman of the Hospital institutional review board. The same 10 contraindications from Cammisa's study were noted. Additional facet arthrosis data were collected, including mention on imaging reports or operating room notes. Clinical notes were reviewed for documentation of range of lumbar motion (ROM) and whether there was restricted or painful extension ROM. Note was made if patients had facet blocks as another clinical indicator of facet arthrosis., Results: All 100 patients had at least one contraindication to TDA. The average was 3.69 (range 1-7). Only one patient had facet arthrosis as their only contraindication. Facet arthrosis was documented on imaging reports or operating room notes in 97/100. Reduced extension was present in 71/75 charts that documented ROM. Facet blocks were performed in 12/100 and gave greater than 50% relief in nine., Conclusions: Both our study and Cammisa's indicate that all lumbar fusion patients in our two institutions have at least one contraindication to TDA. The average fusion patient does not appear to have isolated discogenic pain. A large proportion of the patients appeared to have facet arthritis. The point where facet arthrosis definitely constitutes a contradiction to TDA will require analysis during long-term arthroplasty follow-up studies. Suitable patients for TDA may not represent a significant cohort presently undergoing lumbar fusion.

Background: Rheumatic heart disease (RHD) is still a common form of heart disease among children and young adults, especially in developing countries like India. Between 1940 and 1983, the prevalence rate of RHD varied from 1.8 to 11 per 1000 (national average 6 per 1000), while between 1984 and 1995 the rate varied from 1 to 5.4 per 1000 [1]. The study was carried out to assess the accuracy of a medical student's clinical evaluation of valvular heart disease and compare it with that of an echocardiographic evaluation and to determine the sensitivity, specificity and predictive values of clinical examination as compared to echocardiography for the various lesions in RHD patients., Method: 50 children between the ages of 5-16 years, attending the out patient department or admitted in a large teaching hospital, satisfying the criteria of RHD, were included in the study. Each patient underwent detailed clinical evaluation and relevant investigations including echocardiography., Results: Mitral valve was involved most often both by echocardiography and clinically. Isolated aortic valve involvement was rare. The most common lesion was mitral regurgitation (MR) both by auscultation and by echo. Mixed lesions were seen more often than pure lesions. Mitral stenosis (MS) had the highest sensitivity while tricuspid regurgitation (TR) had the highest specificity. MR had the highest positive predictive value and MS the highest negative predictive value. Sensitivity and specificity of aortic regurgitation (AR) was very low when compared to earlier studies. There was a statistically significant difference between echo diagnosis and clinical diagnosis (p < 0.05)., Conclusion: It is recommended that echocardiography be done routinely for the diagnosis of cardiac lesions in patients of RHD as clinical examination alone can miss various lesions, especially when the lesions are mild or when multiple lesions are present.

The International Association for the Study of Pain, has defined pain as "an unpleasant sensory and emotional experience connected with actual or potential tissue damage or described in terms of such damage". It was thought that the newborn baby does not experience pain because of incompletely developed nervous system. However, it has been shown that neurological system known to be associated with pain transmission and modulation, is intact and functional. A study was conducted in our center to study the analgesic effect of administration of oral glucose in various concentrations, in neonates undergoing heel punctures, for collection of blood for investigations. This was compared with the analgesic effects of breast milk (which contains lactose). 125 full term normal neonates with no history of birth asphyxia or underlying neurological abnormality, requiring heel punctures for collection of blood for various investigations were selected for the study. They were matched for gestational age, birth weight and sex distribution and divided into 5 groups of 25 each. One group comprised control subjects and was administered sterile water. 3 groups were administered 1 ml of varying strengths of glucose solutions i.e. 10%, 25% and 50% respectively. The last group was given 1 ml of expressed breast milk (EBM). Prior to heel pricks, state of arousal, baseline heart rate (HR) and transcutaneous oxygen saturation (SpO2) were recorded by pulse oximeter in each neonate. Autolet, a mechanical device for capillary sampling, was used for heel pricks to give equal strength of painful stimulus in each procedure. Audio tape recorder was used to record the cry. The oral solution was administered slowly over 30 seconds by means of a syringe placed in the mouth. Heel puncture was done after 2 minutes, taking all aseptic precautions. HR and SpO2 were monitored using pulse oximeter. Pain response was assessed, by recording duration of crying, change in HR, change in SpO2 and facial action score after the procedure. Mean duration of cry and total cry over 5 minutes was significantly less in groups given 25% and 50% glucose solutions as compared to the control group and babies given EBM. Difference in mean increase in HR, fall in SpO2 were statistically significant between control group, EBM group and neonates given 25% and 50% glucose solutions respectively. Compared to control group, all other administered solutions (10%, 25%, 50% glucose and EBM) were found to reduce physiological and behavioral responses in neonates undergoing heel punctures. 25% and 50% glucose solutions were found to have maximal analgesic effect and both were found to be equally effective. EBM and 10% glucose solution have an equal analgesic effect but less than 25% or 50% glucose. This simple, cheap and safe method of oral analgesia can be easily used in neonates undergoing heel prick procedures during routine neonatal care.

Bronchial asthma is an inflammatory condition. The inflammatory actions of leukotrienes (LT) B4, C4, D4, and E4 have been shown experimentally to play a role in inflammatory mechanisms, producing asthma. Antileukotrienes (ALT) or leukotrienes antagonists (LA) is a new class of anti-asthma drugs with anti-inflammatory role. LT modifiers from the groups of 5 lipoxygenase inhibitor and Cys LT1 receptor antagonists, are found useful in asthma therapy. LAs are of main use in young infants and toddler with recurrent wheezing, children with moderate to severe chronic asthma on steroid therapy and in allergic rhinitis. In chronic asthma they are required to be used for prolonged periods with other anti-asthma agents. Except for Montelukast and Zafirlukast, which can be used in children above two and six years of age respectively, the paediatric use of other agents is yet to be established. However, these agents are essentially safe. The cost of LAs is reasonably high. At present, with available evidence, these drugs are considered promising in management of asthma in children. However, there is need to do more long term clinical trials for ascertaining their effectivity in different types of asthma to compare their effects with long acting B2 agnoists and chromones, so as to optimally explore their utility.

Objectives: To evaluate efficacy of polymerase chain reaction (PCR), using the insertion sequence IS6110 as target for DNA, to detect Mycobacterium tuberculosis in body fluids of children with suspected tuberculosis (TB)., Setting: Hospitalized patients., Methods: A comparison of PCR on body fluids, Acid Fast Bacilli staining (AFB), mycobacterial culture and clinical features, with special emphasis on central nervous system (CNS) TB was done over 18 month period. A total of 80 children were evaluated, 41 with probable TB disease and 39 controls. Cases were defined by specific clinical criteria. Controls included patients free of clinical TB. PCR was done on the clinical specimens and compared with clinical findings, radiological features, Mantoux (Mx) testing, AFB staining and culture on Lowenstein-Jensen (LJ) medium., Results: Sensitivity of PCR in CSF samples was 100%, in gastric aspirate samples was 20% and in pleural fluid samples was 100%., Conclusion: PCR technique may become a valuable diagnostic tool for the diagnosis of tuberculosis in children especially in CNS TB.

Knee motion is believed to occur about a variable flexion-extension (FE) axis perpendicular to the sagittal plane and a longitudinal rotation (LR) axis. The authors used a mechanical device to locate the FE and the LR axes of six fresh anatomic specimen knees. The motion of points on the LR axis produced circular, planar paths about the fixed FE axis. Magnetic resonance (MR) images in planes perpendicular to the FE axis showed a circular profile for the femoral condyles. The FE axis is constant and directed from anterosuperior on the medial side to posteroinferior on the lateral side, passing through the origins of the medial and lateral collateral ligaments and superior to the crossing point of the cruciates. The LR axis is anterior and not perpendicular to the FE axis, the anatomic planes. This offset produces the valgus and external rotation observed with extension. The implications of two fixed offset axes for knee motion on prosthetic design, braces, gait analysis, and reconstructive surgery are profound.

We used a mechanical method to locate the axis of rotation of the talocrural joint. A single constant axis of rotation was found just distal to the tips of the malleoli. The paths of light-emitting diodes mounted on a talar pin were recorded with time lapse photography during flexion-extension. These paths were analyzed both in the sagittal plane and in a plane perpendicular to the axis of rotation. Sagittal plane studies were distorted by perspective error. The plane used to analyze joint motion or shape must be the plane of motion. Models of the talocrural joint for gait analysis, reconstructive surgery and prosthetic design should have a single offset axis of rotation.