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Purpose: To report a complex case of serpiginous-like choroiditis (SLC) in a patient with anti-neutrophil cytoplasmic antibody (ANCA)-anti-proteinase 3 (PR3)-associated vasculitis with systemic involvement., Methods: Case report., Results: A 40-year-old male from a tuberculosis (TB)-endemic region presented with bilateral active SLC lesions. He was diagnosed with ANCA-PR3 vasculitis with unilateral otitis media, nasopharyngeal mass, lung abscess, pleurisy, and joint pain, all of which responded well to corticosteroids and rituximab. Extensive evaluations and biopsies ruled out Mycobacterium tuberculosis infection. Despite consensus criteria recommending anti-tubercular therapy (ATT), the SLC lesions were effectively managed with an intravitreal dexamethasone implant and systemic azathioprine, showing no recurrence at 18 months without ATT., Conclusions: The development of SLC lesions in the context of systemic autoimmune conditions like ANCA-PR3 vasculitis is uncommon. In these cases, the need for ATT should be carefully evaluated, with close attention to systemic disease manifestations and tailored management strategies.

Background: Human biomonitoring is crucial for regulatory toxicology, yet data on biomarker concentrations in the UAE are lacking. This study addresses this gap by analyzing urinary concentrations of 16 metals in UAE young adults, assessing correlations with personal characteristics, dietary patterns, and lifestyle habits., Methods: A cross-sectional pilot study was conducted among 144 randomly selected young adults (71 males and 73 females) from Sharjah, UAE, between January and March 2023. Participants provided urine samples, which were analyzed for 16 heavy metals using ICP-OES, and completed detailed questionnaires covering sociodemographic factors, lifestyle, and dietary habits. Descriptive statistics were used to summarize participant characteristics, and linear regression analysis was applied to explore associations between metal concentrations and factors such as gender, dietary habits, and exposure to environmental risks. Non-parametric tests, including the Mann-Whitney test, were used to assess differences by gender. Statistical significance was set at p < 0.05. Ethical approval was obtained, and informed consent was secured before participation., Results: Significant findings include dietary influences on metal exposure, with rice consumption linked to higher metal concentrations. Sex differences were significant, with females showing elevated levels of arsenic, lead, and cadmium. Lifestyle factors, such as smoking and incense use, were correlated with increased barium and boron levels., Conclusion: This study highlights the significant role of dietary habits, especially the consumption of rice, in metal exposure among young adults in Sharjah. The findings highlight the urgent need for comprehensive human biomonitoring to understand environmental exposures and reform public health policies. The gender-specific differences in metal distribution suggest the necessity for targeted public health strategies. The study, however, is limited by its cross-sectional nature and the focus on a specific geographic area, warranting further research for broader generalizability. Future investigations, particularly on the impact of incense exposure on metal levels, are essential for developing comprehensive health interventions and preventive strategies in the UAE., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Masarani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Uveitis, which refers to the inflammation of the uveal tract and surrounding structures in the eye, poses a significant risk of vision impairment, with macular edema (UME) being a prevalent complication. The current statement reviews UME's prevalence, pathogenesis, diagnosis, and management strategies, focusing on the utility of systemic and local corticosteroid therapy. Corticosteroids, with their multifaceted effects on inflammatory pathways, serve as the cornerstone of UME treatment. Various administration routes, including topical, periocular, intraocular, and systemic, are employed based on the anatomical type and severity of inflammation. The efficacy of different corticosteroid formulations, such as difluprednate, triamcinolone acetonide, dexamethasone implant, and fluocinolone acetonide implant, is evaluated through clinical trials and retrospective studies. Additionally, the role of corticosteroid-sparing treatments, including antimetabolites like methotrexate and mycophenolate mofetil, is explored. Emerging techniques, such as suprachoroidal space triamcinolone acetonide administration, offer promising alternatives for managing UME. Through a thorough examination of current evidence, this review provides valuable insights into optimizing the management of UME and improving visual outcomes in patients with uveitis.

Introduction: The incidence of infection in open tibial shaft injuries varies with the severity of the injury with rates ranging from roughly 2% for Gustilo-Anderson type I to nearly 43% for type IIIB fractures. As with all fractures, timely antibiotics administration in the emergency department (ED) is an essential component of fracture management and infection prevention. This study identifies factors associated with the expedient administration of antibiotics for open tibial shaft fractures., Methods: This retrospective study identified patients treated for open tibial shaft fractures at an academic level 1 trauma center between 2015 and 2021. Open fractures were identified by reviewing patient charts. We used chart reviews to gather demographics, fracture characteristics, postoperative outcomes, trauma activation, and time to antibiotic order, delivery, and operating room. Univariate analysis was used to compare patients who received antibiotics within 1 h of ED presentation to those who did not. Multivariate analysis was performed to investigate factors associated with faster delivery of antibiotics., Results: Among 70 ED patients with open tibial shaft fractures, 39 (56%) received early administration of antibiotics. Arrival at the ED via emergency medical service (EMS) as opposed to walking in (98% vs. 74%, p = 0.01) and trauma activation (90% vs. 52%, p < 0.001) were significantly more common in the early administration group than the late group. The early group had shorter intervals between antibiotic order and delivery (0.02 h vs. 0.35 h, p = 0.007). Multivariate analysis suggested that trauma activation, EMS arrival, and arrival during non-overnight shifts were independent predictors of a shorter time to antibiotic administration (odds ratios 11.9, 30.7, and 5.4, p = 0.001, 0.016, and 0.013, respectively)., Discussion: Earlier antibiotic delivery is associated with non-overnight arrival at the ED, arrival via EMS, and a coordinated trauma activation. Our findings indicate that in cases where administering antibiotics is critical to achieving positive outcomes, it is advisable to initiate a coordinated trauma response. Furthermore, hospital personnel should be attentive to the need for rapid administration of antibiotics to patients with open fractures who arrive via walk-in or during late-night hours., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Purpose: The Woven EndoBridge (WEB) system has established itself as a safe and effective option for managing wide-neck bifurcation aneurysms. Addressing aneurysms with a greater height than width using conventional WEB-sizing methods has proved ineffective due to the inherent configuration of the devices. To overcome this limitation, we propose an intuitive approach that involves swapping the width and height dimensions of the aneurysm to determine the appropriate WEB size., Materials and Methods: A retrospective analysis was conducted on patients undergoing WEB embolization at a single neuroscience center from March 2013 to February 2023., Results: Twenty-five eligible aneurysms were identified, with the height dimension exceeding the width by an average of 2.33 mm (ranging from 1.4 to 4.5 mm). Of these, 20 cases adhered to the recommended sizing technique, resulting in a 100% success rate of adequate occlusion (14/20 complete occlusion, 6/20 proximal recess filling). In contrast, the outcomes for the remaining 5 cases that did not follow the proposed sizing method were less favorable ( P  < .05). Among these, 4 cases treated with undersized WEBs showed neck remnants during follow-up, and 1 patient who received an oversized WEB required device replacement during the same procedure., Conclusions: The simple sizing method we proposed for treating taller-than-wide aneurysms has demonstrated promising results, allowing the WEB system to address twice the original size range of treatable aneurysms. Further research with a larger sample size is recommended., (© 2024 by American Journal of Neuroradiology.)

The combination of metformin and the peroxisome proliferator-activated receptors (PPAR) agonists offers a promising avenue for managing type 2 diabetes (T2D) through their potential complementary mechanisms of action. The results from randomized controlled trials (RCT) assessing the efficacy of PPAR agonists plus metformin versus metformin alone in T2D are inconsistent, which prompted the conduct of the systematic review and meta-analysis. We searched MEDLINE and EMBASE from inception (1966) to March 2023 to identify all RCTs comparing any PPAR agonists plus metformin versus metformin alone in T2D. Categorical variables were summarized as relative risk along with 95% confidence interval (CI). Twenty RCTs enrolling a total of 6058 patients met the inclusion criteria. The certainty of evidence ranged from moderate to very low. Pooled results show that using PPAR agonist plus metformin, as compared to metformin alone, results in lower concentrations of fasting glucose [MD = - 22.07 mg/dl (95% CI - 27.17, - 16.97), HbA1c [MD = - 0.53% (95% CI - 0.67, - 0.38)], HOMA-IR [MD = - 1.26 (95% CI - 2.16, - 0.37)], and fasting insulin [MD = - 19.83 pmol/L (95% CI - 29.54, - 10.13)] without significant increase in any adverse events. Thus, synthesized evidence from RCTs demonstrates the beneficial effects of PPAR agonist add-on treatment versus metformin alone in T2D patients. In particular, novel dual PPARα/γ agonist (tesaglitazar) demonstrate efficacy in improving glycaemic and lipid concentrations, so further RCTs should be performed to elucidate the long-term outcomes and safety profile of these novel combined and personalized therapeutic strategies in the management of T2D.PROSPERO registration no. CRD42023412603., (© 2024. The Author(s).)

Background: The Woven EndoBridge (WEB) device (MicroVention, Tustin, CA, USA) has an excellent safety profile. While major complications such as device malposition and migration are rare, they can have serious consequences if not addressed promptly. Our case series describes the safety and efficacy of Amplatz goose neck microsnare device (Medtronic in Irvine, CA, USA) in endovascular retrieval of a detached WEB device., Methods: We retrospectively reviewed six consecutive patients who underwent endovascular WEB retrieval using Amplatz microsnare device between March 2012 and December 2022., Results: All six WEB devices were successfully retrieved either directly from the aneurysm sac due to device malpositioning or from a distal branch following device migration. None of the patients experienced intra-operative aneurysm perforation, arterial dissection, or vasospasm attributable to the process of WEB extraction. Five out of six patients (83.3%) had a good functional outcome (mRS 0-1) upon discharge from the hospital and at 24 months., Conclusion: Our experience suggests that detached WEB devices can be safely retrieved using an Amplatz microsnare. Apart from addressing device migration, direct removal of an undersized or malpositioned WEB from the aneurysm sac appears to be a safe option that can be considered when all other rescue techniques have been exhausted., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Despite long-standing uses in several food and medicine traditions, the full potential of the leguminous crop fenugreek (Trigonella foenum-graecum L.) remains to be realized in the modern diet. Not only its seeds, which are highly prized for their culinary and medicinal properties, but also its leaves and stems abound in phytochemicals with high nutritional and health promoting attributes. Fenugreek dual food-medicine applications and reported metabolic activities include hypoglycemic, antihyperlipidemic, antioxidative, anti-inflammatory, antiatherogenic, antihypertensive, anticarcinogenic, immunomodulatory, and antinociceptive effects, with potential organ-protective effects at the cardiovascular, digestive, hepatic, endocrine, and central nervous system levels. Effectiveness in alleviating certain inflammatory skin conditions and dysfunctions of the reproductive system was also suggested. As a food ingredient, fenugreek can enhance the sensory, nutritional, and nutraceutical qualities of a wide variety of foods. Its high nutritive density can assist with the design of dietary items that meet the demand for novelty, variety, and healthier foods. Its seeds provide essential protective nutrients and other bioactive compounds, notably galactomannans, flavonoids, coumarins, saponins, alkaloids, and essential oils, whose health benefits, alone or in conjunction with other bioactives, are only beginning to be tapped into in the food industries. This review summarizes the current state of evidence on fenugreek potential for functional food development, focusing on the nutrients and non-nutrient bioactive components of interest from a dietary perspective, and their applications for enhancing the functional and nutraceutical value of foods and beverages. New developments, safety, clinical evidence, presumed mechanisms of action, and future perspectives are discussed. HIGHLIGHTS: Fenugreek seeds and leaves have long-standing uses in the food-medicine continuum. Fenugreek phytochemicals exert broad-spectrum biological and pharmacological activities. They show high preventive and nutraceutical potential against common chronic diseases. Current evidence supports multiple mechanisms of action mediated by distinct bioactives. Opportunities for fenugreek-based functional foods and nutraceuticals are expanding., (© 2024 Institute of Food Technologists.)

With the increase in respiratory conditions including lung cancer post covid-19 pandemic, drug-loaded nanoparticulate dry powder inhalers (DPIs) can facilitate targeted lung delivery as a patient-friendly, non-invasive method. The aim of this work was to synthesise and optimise iron oxide nanoparticles (IONPs) containing dactinomycin as a model drug, using Quality by Design principles. Chitosan and sodium alginate were investigated as polymeric coatings. The mass median aerodynamic diameter (MMAD), fine particle fraction (FPF), burst-effect (BE), entrapment-efficiency and the emitted-dose (ED) were investigated in initial screening studies and outcomes used to set up a Design of Experiments. Results revealed that chitosan IONPs were superior to that of sodium alginate in delivering DPI with optimal properties [ED (89.9%), FPF (59.7%), MMAD (1.59 µm) and BE (12.7%)]. Design space for targeted IONPs included formulations containing 2.1-2.5% dactinomycin and 0.5-0.9% chitosan. Differential scanning calorimetry and X-ray diffraction and SEM-EDS analysis revealed effective formation of IONPs, and TEM images revealed the production of spherical IONPs with particle size of 4.4 ± 0.77 nm. This work overcame the light sensitivity of dactinomycin to potentially target the high molecular weight drugs to the lungs, with controlled delivery based on a reduced burst effect.

Introduction: Somali women face exceptionally high mortality and incidence rates from both breast cancer (BC) and cervical cancer (CC). They experience the highest age-standardised BC mortality rate in Africa and an age-standardised BC incidence rate of 41.7 per 100,000 women. Somalia's second-highest cancer-related mortality and incidence rates are due to CC, both behind BC. It is critical to identify the underlying factors that may influence healthcare workers' management of both cancers. At present, there is a lack of evidence regarding providers' knowledge of these two cancers and their screening in Somalia., Methods: A cross-sectional questionnaire was administered with a purposive sampling strategy to 469 healthcare professionals and students and was completed by 405 (86%). Healthcare workers were recruited from Mogadishu-based hospitals., Results: One hundred and ninety-seven healthcare professionals and 207 students completed the survey and were included in the analysis. 89% and 73% of respondents demonstrated good knowledge of BC and CC, respectively. Only 46% knew that a vaccine could prevent CC, and 89% of healthcare professionals disagreed that human papillomavirus (HPV) vaccines were available to their patients. Attitudes towards cancer screening, in addition to breast self-examination (BSE), were overwhelmingly positive. For both BC and CC, 24% reported having treated a patient and 30% reported having conducted a screen for either disease., Conclusion: Overall, while knowledge of both diseases and screening was good, there remain areas for clear educational targeting such as HPV vaccine availability and BC preventability. Attitudes to screening for both diseases were exceedingly positive but, with the exception of BSE, failed to translate into practice due to inadequate resources and patient refusal. Future investments into Somalia's chronic care management should prioritise technology necessary to conduct screenings for both diseases, expanding HPV vaccine access and understanding patients' potential motivations for refusing screening., Competing Interests: The authors declare that they have no conflicts of interests. This article is based on a thesis project for completion of graduation requirements for a Master’s in Public Health., (© the authors; licensee ecancermedicalscience.)

The Pediatric Genomics Discovery Program (PGDP) at Yale uses next-generation sequencing (NGS) and translational research to evaluate complex patients with a wide range of phenotypes suspected to have rare genetic diseases. We conducted a retrospective cohort analysis of 356 PGDP probands evaluated between June 2015 and July 2020, querying our database for participant demographics, clinical characteristics, NGS results, and diagnostic and research findings. The three most common phenotypes among the entire studied cohort (n = 356) were immune system abnormalities (n = 105, 29%), syndromic or multisystem disease (n = 103, 29%), and cardiovascular system abnormalities (n = 62, 17%). Of 216 patients with final classifications, 77 (36%) received new diagnoses and 139 (64%) were undiagnosed; the remaining 140 patients were still actively being investigated. Monogenetic diagnoses were found in 67 (89%); the largest group had variants in known disease genes but with new contributions such as novel variants (n = 31, 40%) or expanded phenotypes (n = 14, 18%). Finally, five PGDP diagnoses (8%) were suggestive of novel gene-to-phenotype relationships. A broad range of patients can benefit from single subject studies combining NGS and functional molecular analyses. All pediatric providers should consider further genetics evaluations for patients lacking precise molecular diagnoses., (© 2022 Wiley Periodicals LLC.)

Background: The impact on clinical outcomes of patient selection using perfusion imaging for endovascular thrombectomy (EVT) in patients with acute ischemic stroke presenting beyond 6 hours from onset remains undetermined in routine clinical practice., Methods: Patients from a national stroke registry that underwent EVT selected with or without perfusion imaging (noncontrast computed tomography/computed tomography angiography) in the early (<6 hours) and late (6-24 hours) time windows, between October 2015 and March 2020, were compared. The primary outcome was the ordinal shift in the modified Rankin Scale score at hospital discharge. Other outcomes included functional independence (modified Rankin Scale score ≤2) and in-hospital mortality, symptomatic intracerebral hemorrhage, successful reperfusion (Thrombolysis in Cerebral Infarction score 2b-3), early neurological deterioration, futile recanalization (modified Rankin Scale score 4-6 despite successful reperfusion) and procedural time metrics. Multivariable analyses were performed, adjusted for age, sex, baseline stroke severity, prestroke disability, intravenous thrombolysis, mode of anesthesia (Model 1) and including EVT technique, balloon guide catheter, and center (Model 2)., Results: We included 4249 patients, 3203 in the early window (593 with perfusion versus 2610 without perfusion) and 1046 in the late window (378 with perfusion versus 668 without perfusion). Within the late window, patients with perfusion imaging had a shift towards better functional outcome at discharge compared with those without perfusion imaging (adjusted common odds ratio [OR], 1.45 [95% CI, 1.16-1.83]; P =0.001). There was no significant difference in functional independence (29.3% with perfusion versus 24.8% without; P =0.210) or in the safety outcome measures of symptomatic intracerebral hemorrhage ( P =0.53) and in-hospital mortality (10.6% with perfusion versus 14.3% without; P =0.053). In the early time window, patients with perfusion imaging had significantly improved odds of functional outcome (adjusted common OR, 1.51 [95% CI, 1.28-1.78]; P =0.0001) and functional independence (41.6% versus 33.6%, adjusted OR, 1.31 [95% CI, 1.08-1.59]; P =0.006). Perfusion imaging was associated with lower odds of futile recanalization in both time windows (late: adjusted OR, 0.70 [95% CI, 0.50-0.97]; P =0.034; early: adjusted OR, 0.80 [95% CI, 0.65-0.99]; P =0.047)., Conclusions: In this real-world study, acquisition of perfusion imaging for EVT was associated with improvement in functional disability in the early and late time windows compared with nonperfusion neuroimaging. These indirect comparisons should be interpreted with caution while awaiting confirmatory data from prospective randomized trials.

In this study, we formulated Thymoquinone-loaded nanocomposites (TQ-NCs) using high-pressure homogenizer without sodium tripolyphosphate. The TQ-NCs were characterized and their anti-inflammatory determined by the response of the LPS-stimulated macrophage RAW 264.7 cells in the production of nitric oxide, prostaglandin E2, tumor necrosis factor-α, interleukin-6, and interleukin-1β. The physicochemical properties of TQ-NC were determined using different machines. TQ was fully incorporated in the highly thermal stable nanoparticles. The nanoparticles showed rapid release of TQ in the acidic medium of the gastric juice. In medium of pH 6.8, TQ-NC exhibited sustained release of TQ over a period of 100 h. The results suggest that TQ-NC nanoparticles have potential application as parenterally administered therapeutic compound. TQ-NC effectively reduce production of inflammatory cytokines by the LPS-stimulated RAW 264.7 cells, indicating that they have anti-inflammatory properties. In conclusion, TQ-NC nanoparticles have the characteristics of efficient carrier for TQ and an effective anti-inflammatory therapeutic compound., Competing Interests: 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., (© 2022 The Author(s).)

Introduction: Vaccine-preventable disease outbreaks have increased in past years, and there is great public health interest in monitoring attitudes towards vaccination as well as identifying factors contributing to vaccine hesitancy and refusal. Although the WHO declared vaccine hesitancy as one of the top threats to global health in 2019, studies focused on the determinants and extent of vaccine hesitancy in Arab countries in the Middle East and North Africa (MENA) region are lacking. This scoping review explores the various factors surrounding vaccine hesitancy, including but not limited to geographic, cultural and religious factors, and examines the extent and nature of the existing evidence on this topic. In light of current development of various COVID-19 vaccines, our work seeks to elucidate the barriers to vaccine uptake in specific populations., Methods and Analysis: This review will be conducted using the Joanna Briggs Institute Manual for Scoping Reviews. It will comply with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. Studies published in English, Arabic and French between January 1998 and December 2020 will be drawn from PubMed, Embase, Cochrane and Scopus. The search strategy will include terms related to vaccination and vaccine hesitancy in Arab countries in the MENA region. We will also include grey literature on the topic by searching Google and Google Scholar. Studies will be selected according to the Participants-Intervention-Comparators-Outcome model, and all study titles and abstracts will be screened by two reviewers. Disagreements will be resolved with a third reviewer's input., Ethics and Dissemination: This review is exempted from ethical approval and will be published in a peer-reviewed open-access journal to ensure wide dissemination., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Since psychiatric staff experience a high occurrence of workplace violence and subsequent Posttraumatic Stress Disorder (PTSD), it is important to assess the behavioral and cognitive risk factors of PTSD in this population., Objective: The current study assesses the incidence of PTSD 12 months after the occurrence of WV. Furthermore, it examines possible prospective associations between coping strategies and cognitive appraisals, respectively, and PTSD., Methods: This prospective cohort study was conducted with staff from 18 psychiatric wards in Denmark (n = 183) who had reported an incidence of workplace violence. Most subjects were women (83.3%)., Results: The incidence of PTSD was 9.8%. The main analysis showed a significant relationship between negative cognitive appraisals about the self and PTSD (OR = 2.87, p < .05), and a coping strategy of self-blame and PTSD (OR = 2.21, p < .05)., Conclusions: Certain dysfunctional coping strategies and negative cognitive appraisals seems to predict posttraumatic stress in an occupational context. Information about these processes could be important for preventive strategies in the workplace.

Reports of a rare form of cerebral venous sinus thrombosis with profound thrombocytopenia have emerged following introduction of the adenovirus-vectored coronavirus disease 2019 (COVID-19) vaccines. Between March and June 2021, seven cases of refractory vaccine-induced immune thrombotic thrombocytopenia were referred to our institution for mechanical thrombectomy. The condition of 1 patient deteriorated during interhospital transfer, and the remaining 6 underwent successful recanalization. No procedure-related adverse events were reported. At the time of this writing, 3 patients have been discharged with a good functional outcome (mRS 0-1), one required rehabilitation for mild dysarthria and vocal cord palsy (mRS 3), and 2 have died due to severe mass effect. Our anecdotal experience suggests that endovascular therapy may be safe and effective in reducing thrombus burden in selected cases of postvaccination cerebral venous sinus thrombosis., (© 2022 by American Journal of Neuroradiology.)

Background: Somalia is considered severely underprepared to contain an outbreak of COVID-19, with critical shortages in healthcare personnel and treatment resources. In limited-resource settings such as Somalia, providing healthcare workers with adequate information on COVID-19 is crucial to improve patient outcomes and mitigate the spread of the SARS-CoV-2 virus. This study assessed the knowledge of, preparedness for, and perceptions toward COVID-19 prevention and treatment among Somali healthcare workers., Methods: A descriptive, cross-sectional survey was completed by 364 Somali healthcare workers in summer of 2020 utilizing a convenience sampling method., Results: Participants' most accessed sources of COVID-19 information were from social media (64.8%), official government and international health organization websites (51.1%,), and traditional media sources such as radio, TV, and newspapers (48.1%). A majority of participants demonstrated strong knowledge of treatment of COVID-19, the severity of COVID-19, and the possible outcomes of COVID-19, but only 5 out of 10 symptoms listed were correctly identified by more than 75% of participants. Although participants indicated seeing a median number of 10 patients per week with COVID-19 related symptoms, access to essential medical resources, such as N95 masks (30.2%), facial protective shields (24.5%), and disposable gowns (21.4%), were limited. Moreover, 31.3% agreed that Somalia was in a good position to contain an emerging outbreak of COVID-19. In addition, 40.4% of participants agreed that the Somali government's response to the pandemic was sufficient to protect Somali healthcare professionals., Conclusion: This study provides evidence for the need to equip Somali healthcare providers with more information, personal protective equipment, and treatment resources such that they can safely and adequately care for COVID-19 patients and contain the spread of the virus. Social media and traditional news outlets may be effective outlets to communicate information regarding COVID-19 and the Somali government's response to frontline healthcare workers., Competing Interests: The authors have declared that no competing interests exist.

Objectives: This study examined knowledge and perceptions of COVID-19, prevalence of pre-existing conditions and access to essential resources among residents of internally displaced person (IDP) camps in Somalia, where overcrowded settlements with weakened infrastructure, inadequate water, sanitation, and hygiene facilities, and limited access to health services make this vulnerable population particularly susceptible to a COVID-19 outbreak., Design: A descriptive, cross-sectional survey., Setting: Twelve IDP camps across six areas of the Lower Shabelle region in Somalia., Participants: 401 adult Somali IDP camp residents., Results: The majority of participants were female (86%) and had received no formal education (89%). While 58% reported being in 'good' health, half of the participants reported having one or more pre-existing conditions. Though 77% of respondents reported taking at least one COVID-19 preventative public health measure, respondents reported a lack of access to adequate sanitation, an inability to practice social distancing and nearly universal inability to receive a COVID-19 screening exam. Questions assessing knowledge surrounding COVID-19 prevention and treatment yielded answers of 'I don't know' for roughly 50% of responses. The majority of participants were not familiar with basic information about the virus or confident that they could receive medical services if infected. 185 (47%) respondents indicated that camp living conditions needed to change to prevent the spread of COVID-19., Conclusion: This study highlights low levels of COVID-19 knowledge and limited access to essential prevention and treatment resources among individuals living in Somali IDP camps. A massive influx of additional resources is required to adequately address COVID-19 in Somalia, starting with codesigning interventions to educate those individuals most vulnerable to infection., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Psychiatric staff is at risk of workplace violence (WV) and subsequent posttraumatic symptomatology. The current study assesses the prevalence of acute stress disorder (ASD) and posttraumatic stress disorder (PTSD) in psychiatric staff following WV. This also examines the prospective association between ASD and PTSD., Methods: This is a prospective cohort study of staff from 18 psychiatric wards in Denmark (n = 250), that reported an incident of workplace violence., Results: The prevalence of ASD was 10.8%, while 8% had PTSD 3 months post-assault. Generalized linear mixed models showed a significant predictive power of ASD on PTSD (OR 8.45, p < 0.001) in the fully adjusted model., Conclusions: ASD seems to be a predictor of future PTSD in an occupational context and should be considered a possible instrument in enactment of preventive strategies.

Recessive variants in the GLDN gene, which encodes the gliomedin protein and is involved in nervous system development, have recently been associated with Arthrogryposis Multiplex Congenita (AMC), a heterogenous condition characterized by congenital contractures of more than one joint. Two cohorts of patients with GLDN-associated AMC have previously been described, evolving the understanding of the condition from lethal to survivable with the provision of significant neonatal support. Here, we describe one additional patient currently living with the syndrome, having one novel variant, p.Leu365Phe, for which we provide functional data supporting its pathogenicity. We additionally provide experimental data for four other previously reported variants lacking functional evidence, including p.Arg393Lys, the second variant present in our patient. We discuss unique and defining clinical features, adding calcium-related findings which appear to be recurrent in the GLDN cohort. Finally, we compare all previously reported patients and draw new conclusions about scope of illness, with emphasis on the finding of pulmonary hypoplasia, suggesting that AMC secondary to GLDN variants may be best fitted under the umbrella of fetal akinesia deformation sequence (FADS)., (© 2020 Wiley Periodicals LLC.)

Background/purpose: Preoperative radiographic examination of mandibular third molars (MTM) is essential to prevent inferior alveolar nerve (IAN) injury. The aim of this study was to assess the panoramic radiography (PAN) signs considered as indicators of increased risk of IAN injury and to correlate them with the cone beam CT (CBCT) findings., Materials and Methods: 58 patients who had MTMs extraction between January 2012 and January 2018. OPG were evaluated for the following signs: interruption of the roof of the canal, root darkening, roots deflection and narrowing, canal deviation, superimposition between the MTM roots and mandibular canal. Loss of canal cortication, root grooving, thinning and perforation of lingual cortex were assessed in CBCT images. Chi-square test and multivariate logistic regression tests were used to test the relationship between PAN signs and CBCT findings., Results: A total of 79 MTMs were examined. Loss of canal cortication in CBCT was seen in 22 (27.8%) of the cases. Root darkening in PAN images was the most frequent radiographic sign. Canal deviation and interruption of white line in PAN demonstrated a statistically significant correlation with the loss of canal cortication between the MTM and the mandibular canal on CBCT images (p = 0.004 and p = 0.012, respectively). No statistically significant association was observed for the other PAN signs and CBCT findings., Conclusion: Canal deviation and interruption of white lines were associated with loss of canal cortication on CBCT, indicating a direct contact between the roots and the mandibular canal which required a further assessment prior to the extraction., Competing Interests: None declared., (© 2019 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)

Background: Heterogeneity is a major obstacle to developing effective treatments for patients with primary Sjögren's syndrome. We aimed to develop a robust method for stratification, exploiting heterogeneity in patient-reported symptoms, and to relate these differences to pathobiology and therapeutic response., Methods: We did hierarchical cluster analysis using five common symptoms associated with primary Sjögren's syndrome (pain, fatigue, dryness, anxiety, and depression), followed by multinomial logistic regression to identify subgroups in the UK Primary Sjögren's Syndrome Registry (UKPSSR). We assessed clinical and biological differences between these subgroups, including transcriptional differences in peripheral blood. Patients from two independent validation cohorts in Norway and France were used to confirm patient stratification. Data from two phase 3 clinical trials were similarly stratified to assess the differences between subgroups in treatment response to hydroxychloroquine and rituximab., Findings: In the UKPSSR cohort (n=608), we identified four subgroups: Low symptom burden (LSB), high symptom burden (HSB), dryness dominant with fatigue (DDF), and pain dominant with fatigue (PDF). Significant differences in peripheral blood lymphocyte counts, anti-SSA and anti-SSB antibody positivity, as well as serum IgG, κ-free light chain, β2-microglobulin, and CXCL13 concentrations were observed between these subgroups, along with differentially expressed transcriptomic modules in peripheral blood. Similar findings were observed in the independent validation cohorts (n=396). Reanalysis of trial data stratifying patients into these subgroups suggested a treatment effect with hydroxychloroquine in the HSB subgroup and with rituximab in the DDF subgroup compared with placebo., Interpretation: Stratification on the basis of patient-reported symptoms of patients with primary Sjögren's syndrome revealed distinct pathobiological endotypes with distinct responses to immunomodulatory treatments. Our data have important implications for clinical management, trial design, and therapeutic development. Similar stratification approaches might be useful for patients with other chronic immune-mediated diseases., Funding: UK Medical Research Council, British Sjogren's Syndrome Association, French Ministry of Health, Arthritis Research UK, Foundation for Research in Rheumatology. VIDEO ABSTRACT., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Thymoquinone is an effective phytochemical compound in the treatment of various diseases. However, its practical administration has been limited due to poor aqueous solubility and bioavailability. In this work, we developed a novel inclusion complex of thymoquinone and hydroxypropyl-β-cyclodextrin that features improved solubility and bioactivity. The drug solubility was markedly accelerated in the increasing ratio of hydroxypropyl-β-cyclodextrin to thymoquinone amount. The formation of the thymoquinone/hydroxypropyl-β-cyclodextrin inclusion complex was evidenced using X-ray diffraction, differential scanning calorimetry, thermal gravimetric analysis, Fourier transform infrared, scanning electron microscopy and nuclear magnetic resonance. The release behavior of the complex, as well as of their mixtures, was examined in artificial gastric (pH 1.2) and intestinal (pH 6.8) dissolution media. The formulated complex released the drug rapidly at the initial stage, followed by a slow release. Thermodynamic parameters ΔH, ΔS and ΔG were calculated with temperatures ranging from 20 to 45 °C to evaluate the complexation process. The activity of the inclusion complex was evaluated on IgE-mediated allergic response in rat basophilic leukemia (RBL-2H3) cells by monitoring key allergic mediators. The results revealed that compared with free thymoquinone, the inclusion complex more strongly inhibited the release of histamine, tumor necrosis factor-α, and interleukin-4, and was not cytotoxic at the tested thymoquinone concentrations (0.125-4 μg/mL) indicating the inclusion complex possibly had better antiallergic effects. Our finding suggested that the inclusion complex achieved prolonged action and reduced side-effect of thymoquinone., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: To assess the relationships between systemic IFN type I (IFN-I) and II (IFN-II) activity and disease manifestations in primary SS (pSS)., Methods: RT-PCR of multiple IFN-induced genes followed by principal component analysis of whole blood RNA of 50 pSS patients was used to identify indicator genes of systemic IFN-I and IFN-II activities. Systemic IFN activation levels were analysed in two independent European cohorts (n = 86 and 55, respectively) and their relationships with clinical features were analysed., Results: Three groups could be stratified according to systemic IFN activity: IFN inactive (19-47%), IFN-I (53-81%) and IFN-I + II (35-55%). No patient had isolated IFN-II activation. IgG levels were highest in patients with IFN-I + II, followed by IFN-I and IFN inactive patients. The prevalence of anti-SSA and anti-SSB was higher among those with IFN activation. There was no difference in total-EULAR SS Disease Activity Index (ESSDAI) or ClinESSDAI between the three subject groups. For individual ESSDAI domains, only the biological domain scores differed between the three groups (higher among the IFN active groups). For patient reported outcomes, there were no differences in EULAR Sjögren's syndrome patient reported index (ESSPRI), fatigue or dryness between groups, but pain scores were lower in the IFN active groups. Systemic IFN-I but not IFN-I + II activity appeared to be relatively stable over time., Conclusions: Systemic IFN activation is associated with higher activity only in the ESSDAI biological domain but not in other domains or the total score. Our data raise the possibility that the ESSDAI biological domain score may be a more sensitive endpoint for trials targeting either IFN pathway.

Development of appropriate models, based on an in-depth understanding of the wash-off process, is essential to accurately estimating pollutant loads transported by stormwater, thereby minimizing environmental contamination. To this end, we developed an innovative rainfall simulator, which simulated an intense rainfall (120mm/h) and permitted the acquisition of runoff samples as well as the in situ monitoring of continuous flow and turbidity dynamics. Relationships between deposited sediments and total suspended solids in simulated runoff were thus investigated on two different types of surfaces within the Paris region in terms of loads and particle size distribution. Results demonstrate the occurrence of first flush phenomenon on the sidewalks even under constant flow. Results also show that the highest fraction conveyed by runoff consisted of fine (<16μm) and medium-sized (<100μm) particles, whose detachment was more favorable from smooth surfaces than from rougher ones. In terms of stormwater quality modelling, results suggest that the integration of a wash-off fraction based on both particle size and rainfall intensity could be an entrance for a better prediction of stormwater pollution., (Copyright © 2017 Elsevier B.V. All rights reserved.)

A deep understanding of pollutant buildup and wash-off is essential for accurate urban stormwater quality modeling and for the development of stormwater management practices, knowing the potential adverse impacts of runoff pollution on receiving waters. In the context of quantifying the contribution of airborne pollutants to the contamination of stormwater runoff and assessing the need of developing an integrated AIR-WATER modeling chain, loads of polycyclic aromatic hydrocarbons (PAHs) and metal trace elements (MTEs) are calculated in atmospheric dry deposits, stormwater runoff, and surface dust stock within a small yet highly trafficked urban road catchment (~ 30,000 vehicles per day) near Paris. Despite the important traffic load and according to the current definition of "atmospheric" source, atmospheric deposition did not account for more than 10% of the PAHs and trace metal loads in stormwater samples for the majority of the events, based on the ratio of deposition to stormwater. This result shows that atmospheric deposition is not a major source of pollutants in stormwater, and thus, linking the air and water compartment in a modeling chain to have more accurate estimates of pollutant loads in stormwater runoff might not be relevant. Comparison of road dust with water samples demonstrates that only the fine fraction of the available stock is eroded during a rainfall event. Even if the atmosphere mostly generates fine particles, the existence of other sources of fine particles to stormwater runoff is highlighted.

The leukocyte heat shock response (HSR) is used to determine individual's thermotolerance. The HSR and thermotolerance are enhanced following interventions such as preconditioning and/or acclimation/acclimatization. However, it is unclear whether the leukocyte HSR is an appropriate surrogate for the HSR in other tissues implicated within the pathophysiology of exertional heat illnesses (e.g., skeletal muscle), and whether an acute preconditioning strategy (e.g., downhill running) can improve subsequent thermotolerance. Physically active, non-heat acclimated participants were split into two groups to investigate the benefits of hot downhill running as preconditioning strategy. A hot preconditioning group (HPC; n = 6) completed two trials (HPC1 HOTDOWN and HPC2 HOTDOWN ) of 30 min running at lactate threshold (LT) on -10% gradient in 30°C and 50% relative humidity (RH) separated by 7 d. A temperate preconditioning group (TPC; n = 5) completed 30 min running at LT on a -1% gradient in 20°C and 50% (TPC1 TEMPFLAT ) and 7 d later completed 30 min running at LT on -10% gradient in 30°C and 50% RH (TPC2 HOTDOWN ). Venous blood samples and muscle biopsies (vastus lateralis; VL) were obtained before, immediately after, 3, 24, and 48 h after each trial. Leukocyte and VL Hsp72, Hsp90α, and Grp78 mRNA relative expression was determined via RT-QPCR. Attenuated leukocyte and VL Hsp72 (2.8 to 1.8 fold and 5.9 to 2.4 fold; p < 0.05) and Hsp90α mRNA (2.9 to 2.4 fold and 5.2 to 2.4 fold; p < 0.05) responses accompanied reductions ( p < 0.05) in physiological strain [exercising rectal temperature (-0.3°C) and perceived muscle soreness (~ -14%)] during HPC2 HOTDOWN compared to HPC1 HOTDOWN (i.e., a preconditioning effect). Both VL and leukocyte Hsp72 and Hsp90α mRNA increased ( p < 0.05) simultaneously following downhill runs and demonstrated a strong relationship ( p < 0.01) of similar magnitudes with one another. Hot downhill running is an effective preconditioning strategy which ameliorates physiological strain, soreness and Hsp72 and Hsp90α mRNA responses to a subsequent bout. Leukocyte and VL analyses are appropriate tissues to infer the extent to which the HSR has been augmented.

Background: Chronic Fatigue Syndrome (CFS) is a prevalent debilitating condition that affects approximately 250,000 people in the UK. There is growing interest in the role of mitochondrial function and mitochondrial DNA (mtDNA) variation in CFS. It is now known that fatigue is common and often severe in patients with mitochondrial disease irrespective of their age, gender or mtDNA genotype. More recently, it has been suggested that some CFS patients harbour clinically proven mtDNA mutations., Methods: MtDNA sequencing of 93 CFS patients from the United Kingdom (UK) and South Africa (RSA) was performed using an Ion Torrent Personal Genome Machine. The sequence data was examined for any evidence of clinically proven mutations, currently; more than 200 clinically proven mtDNA mutations point mutations have been identified., Results: We report the complete mtDNA sequence of 93 CFS patients from the UK and RSA, without finding evidence of clinically proven mtDNA mutations. This finding demonstrates that clinically proven mtDNA mutations are not a common element in the aetiology of disease in CFS patients. That is patients having a clinically proven mtDNA mutation and subsequently being misdiagnosed with CFS are likely to be rare., Conclusion: The work supports the assertion that CFS should not be considered to fall within the spectrum of mtDNA disease. However, the current study cannot exclude a role for nuclear genes with a mitochondrial function, nor a role of mtDNA population variants in susceptibility to disease. This study highlights the need for more to be done to understand the pathophysiology of CFS.

Aim: To determine whether three-dimensional (3D) reconstruction from conventional magnetic resonance imaging (MRI) is able to accurately detect a meniscal tear, and define the configuration., Methods: Thirty-three patients' 3T MRI scan data were collected and sagittal uni-planar 3D reconstructions performed from the preoperative MRI. There were 24 meniscal tears in 24 patients, and nine controls. All patients had arthroscopic corroboration of MRI findings. Two independent observers prospectively reported on all 33 reconstructions. Meniscal tear presence or absence was noted, and tear configuration subsequently categorised as either radial, bucket-handle, parrot beak, horizontal or complex., Results: Identification of control menisci or meniscal tear presence was excellent (Accuracy: observer 1 = 90.9%; observer 2 = 81.8%). Of the tear configurations, bucket handle tears were accurately identified (Accuracy observer 1 and 2 = 80%). The remaining tear configurations were not accurately discernable., Conclusion: Uni-planar 3D reconstruction from 3T MRI knee scan sequences are useful in identifying normal menisci and menisci with bucket-handle tears. Advances in MRI sequencing and reconstruction software are awaited for accurate identification of the remaining meniscal tear configurations., Competing Interests: Conflict-of-interest statement: None of the authors have any conflict of interest or anything to disclose related to the research performed.

Between 19 April and 23 June 2015, 52 laboratory-confirmed cases of Middle East Respiratory Syndrome due to coronavirus (MERS) were reported from Al-Ahssa region, eastern Saudi Arabia. The first seven cases occurred in one family; these were followed by 45 cases in three public hospitals. The objectives of this investigation were to describe the epidemiological characteristic of the cluster and identify potential risk factors and control measures to be instituted to prevent further occurrence of MERS. We obtained the medical records of all confirmed cases, interviewed the members of the affected household and reviewed the actions taken by the health authorities. All the cases were connected. The index case was a 62-year-old man with a history of close contact with dromedary camels; three of the seven infected family members and 18 people in hospitals died (case-fatality rate, 40.4%). The median incubation period was about 6 days. The cluster of cases appeared to be due to high exposure to MERS, delayed diagnosis, inadequate risk communication and inadequate compliance of hospital health workers and visitors with infection prevention and control measures.

Objective: Patients with systemic vasculitis (SV) have an increased risk of all-cause mortality, often due to infection, compared to the healthy population. We investigated whether humoral response to vaccination and biomarkers of immune dysfunction were associated with infection and death., Methods: Patients with SV in remission were vaccinated with pneumococcal 7-valent conjugate, Haemophilus influenzae type b, and meningococcal group C conjugate vaccine and meningococcal polysaccharide groups A, C, Y, and W135 vaccines. Total IgG and antibody titers against specific antigens and lymphocyte subset analysis were performed before vaccination. Postvaccination antibody titers were measured at 4 weeks and 2 years, from which an antibody response score was calculated. Infections and death following vaccination were collected prospectively following vaccination., Results: A total of 92 patients were safely vaccinated with no increase in disease relapse, median followup 4.6 years (interquartile range [IQR] 3.6-4.8 years). Eighteen patients died at a median of 2 years and the overall infection rate was 0.4 (IQR 0.2-1.3) infections/patient/year. Reduced serum IgG, B cell count, and CD4+ cell counts predicted poor vaccine response and infection but not death. The response rates to individual vaccine antigens was highly variable, with a median response rate of 46% (IQR 39-58%) of patients responding to each individual antigen. Vaccine response, age, and reduced renal function were independent predictors of all-cause mortality in multivariate analysis., Conclusion: Total IgG and B cell counts predict infection and response to vaccination. Vaccination in patients with SV in remission is safe and the response predicts all-cause mortality. Vaccine response is a surrogate marker of immune system health., (© 2016, American College of Rheumatology.)

Vaccinia virus (VACV) is one of the most extensively-studied viruses of the Poxviridae family. It is easy to genetically modify, so it has become a key tool for many applications. In this context, reporter genes facilitate the study of the role of foreign genes introduced into the genome of VACV. In this review, we describe the type of reporter genes that have been used to generate reporter-expressing VACV and the applications of the recombinant viruses obtained. Reporter-expressing VACV are currently employed in basic and immunology research, in the development of vaccines and cancer treatment.

Acne vulgaris is one of the most common chronic inflammatory skin disorders among adolescents and young adults. It is associated with substantial morbidity and, rarely, with mortality. The exact worldwide incidence and prevalence are currently unknown. Current challenges involve improving understanding of the underlying pathophysiology of acne vulgaris and developing a practical treatment consensus. Expert panel discussions were held in 2013 and 2014 among a group of scientists and clinicians from the Omani and United Arab Emirate Dermatology Societies to ascertain the current optimal management of acne vulgaris, identify clinically relevant end-points and construct suitable methodology for future clinical trial designs. This article reviews the discussions of these sessions and recent literature on this topic.

Background: Fatigue is a debilitating condition with a significant impact on patients' quality of life. Fatigue is frequently reported by patients suffering from primary Sjögren's Syndrome (pSS), a chronic autoimmune condition characterised by dryness of the eyes and the mouth. However, although fatigue is common in pSS, it does not manifest in all sufferers, providing an excellent model with which to explore the potential underpinning biological mechanisms., Methods: Whole blood samples from 133 fully-phenotyped pSS patients stratified for the presence of fatigue, collected by the UK primary Sjögren's Syndrome Registry, were used for whole genome microarray. The resulting data were analysed both on a gene by gene basis and using pre-defined groups of genes. Finally, gene set enrichment analysis (GSEA) was used as a feature selection technique for input into a support vector machine (SVM) classifier. Classification was assessed using area under curve (AUC) of receiver operator characteristic and standard error of Wilcoxon statistic, SE(W)., Results: Although no genes were individually found to be associated with fatigue, 19 metabolic pathways were enriched in the high fatigue patient group using GSEA. Analysis revealed that these enrichments arose from the presence of a subset of 55 genes. A radial kernel SVM classifier with this subset of genes as input displayed significantly improved performance over classifiers using all pathway genes as input. The classifiers had AUCs of 0.866 (SE(W) 0.002) and 0.525 (SE(W) 0.006), respectively., Conclusions: Systematic analysis of gene expression data from pSS patients discordant for fatigue identified 55 genes which are predictive of fatigue level using SVM classification. This list represents the first step in understanding the underlying pathophysiological mechanisms of fatigue in patients with pSS.

The suitability of a commonly used accumulation and wash-off model for continuous modelling of urban runoff contamination was evaluated based on 11-month turbidity and flow-rate records from an urban street. Calibration and uncertainty analysis were performed using a Markov Chain Monte-Carlo sampling method for both suspended solids loads (discharge rates) and concentration modelling. Selected models failed at replicating suspended solids concentration over the complete monitoring period. The studied dataset indeed suggests that the accumulation process is rather unpredictable and cannot be satisfactorily represented with usual accumulation models unless short periods are considered. Regarding suspended solid loads modelling, noticeably better performance was achieved, but similar results could as well be obtained with much simpler constant concentration models. Unless providing very accurate estimates of concentrations in runoff, accounting for their temporal variability during rain events may therefore not always be necessary for pollutant loads modelling, as loads are in fact mostly explained by runoff volumes., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The mylohyoid hiatus and hernia were discovered in the nineteenth century and were considered to explain the origin of the plunging ranula from the sublingual gland. This formed the rationale for sublingual sialadenectomy for the treatment of plunging ranula. However, a more recent, extensive histological investigation reported that hernias contained submandibular gland, which supported an origin of the plunging ranula from the submandibular gland and submandibular sialadenectomy for the treatment of plunging ranula. We therefore decided to investigate the occurrence and location of the hiatus and the histological nature of the hernia. Twenty-three adult cadavers were dissected in the submandibular region. The locations and dimensions of mylohyoid hiatuses were measured before taking biopsies of hernias. Hiatuses with associated hernias were found in ten cadavers: unilateral in six; and bilateral in four, in one of which there were three hiatuses. Sublingual gland was identified in nine hernias and fat without gland in six. This investigation supports clinical and experimental evidence that the plunging ranula originates from the sublingual gland and may enter the neck through the mylohyoid muscle. It confirms the rationale of sublingual sialadenectomy for the treatment of plunging ranula., (Copyright © 2013 Wiley Periodicals, Inc.)

The long-term objective of the present study was to determine the ability of NiZn ferrite nanoparticles to kill cancer cells. NiZn ferrite nanoparticle suspensions were found to have an average hydrodynamic diameter, polydispersity index, and zeta potential of 254.2 ± 29.8 nm, 0.524 ± 0.013, and -60 ± 14 mV, respectively. We showed that NiZn ferrite nanoparticles had selective toxicity towards MCF-7, HepG2, and HT29 cells, with a lesser effect on normal MCF 10A cells. The quantity of Bcl-2, Bax, p53, and cytochrome C in the cell lines mentioned above was determined by colorimetric methods in order to clarify the mechanism of action of NiZn ferrite nanoparticles in the killing of cancer cells. Our results indicate that NiZn ferrite nanoparticles promote apoptosis in cancer cells via caspase-3 and caspase-9, downregulation of Bcl-2, and upregulation of Bax and p53, with cytochrome C translocation. There was a concomitant collapse of the mitochondrial membrane potential in these cancer cells when treated with NiZn ferrite nanoparticles. This study shows that NiZn ferrite nanoparticles induce glutathione depletion in cancer cells, which results in increased production of reactive oxygen species and eventually, death of cancer cells.

In this study, in vitro cytotoxicity of nickel zinc (NiZn) ferrite nanoparticles against human colon cancer HT29, breast cancer MCF7, and liver cancer HepG2 cells was examined. The morphology, homogeneity, and elemental composition of NiZn ferrite nanoparticles were investigated by scanning electron microscopy, transmission electron microscopy, and energy dispersive X-ray spectroscopy, respectively. The exposure of cancer cells to NiZn ferrite nanoparticles (15.6-1,000 μg/mL; 72 hours) has resulted in a dose-dependent inhibition of cell growth determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The quantification of caspase-3 and -9 activities and DNA fragmentation to assess the cell death pathway of the treated cells showed that both were stimulated when exposed to NiZn ferrite nanoparticles. Light microscopy examination of the cells exposed to NiZn ferrite nanoparticles demonstrated significant changes in cellular morphology. The HepG2 cells were most prone to apoptosis among the three cells lines examined, as the result of treatment with NiZn nanoparticles. In conclusion, NiZn ferrite nanoparticles are suggested to have potential cytotoxicity against cancer cells.

Background: Previous studies of task-specific skills have suggested that a loss of technical performance occurs if the skill is not practiced for a six-month period. The aims of this study were to objectively demonstrate the learning curve for a complex arthroscopic task (meniscal repair) by means of motion analysis and to determine the impact of task repetition on the retention of this skill., Methods: Nineteen orthopaedic residents with experience in routine knee arthroscopy but not in arthroscopic meniscal repair were recruited into a randomized study. During the initial learning phase, all subjects performed twelve meniscal repairs on a knee simulator over a three-week period. A validated motion analysis tracking system was used to objectively record the performance and learning of each subject; the outcomes were the time taken, distance traveled, and number of hand movements. The subjects were then randomized into three groups. Group A performed one meniscal repair each month, Group B performed one meniscal repair at three months, and Group C performed no repairs during this interim phase. All three groups then returned at the six-month point for the final assessment phase, during which they carried out an additional twelve meniscal repairs over three weeks., Results: All subjects demonstrated a clear learning curve during the initial learning phase, with significant objective improvement in all motion analysis parameters over the initial twelve episodes (p < 0.0001). Although some residents had reached a learning plateau by twelve episodes, others continued to make further improvements for up to another nine episodes. Importantly, Group C did not display any loss of skill between the initial learning phase and final evaluation phase despite a six-month break in task repetition (p > 0.05)., Conclusions: In contrast to previous studies, residents did not lose any skill over a six-month interruption in task performance, and other residents took longer to produce a more consistent performance.

Background: Restrictions placed on the working hours of doctors over the past decade have resulted in substantial changes to the training and assessment of orthopaedic surgical residents. Many who are responsible for training the surgeons of the future have become concerned that this reduced clinical exposure is having a detrimental impact on technical skill acquisition. Consequently, there is a need for surgical educators to develop more objective methods for assessing surgical skill. The primary aim of this study was to determine whether a novel set of visual parameters assessing visuospatial ability, fine motor dexterity, and gaze control could objectively discriminate among various levels of arthroscopic experience. The secondary aim was to evaluate the correlations between these new parameters and previously established technical skill assessment methods., Methods: Twenty-seven subjects were divided into a novice group (n = 7), a resident group (n = 15), and an expert group (n = 5) on the basis of arthroscopic experience. All subjects performed a diagnostic knee arthroscopy task on a simulator. Their performance was assessed with use of novel simple visual parameters that included the prevalence of instrument loss, triangulation time, and prevalence of lookdowns. Performance was also evaluated with use of previously validated technical skill assessment methods (a global rating scale and motion analysis)., Results: A significant difference in performance among the groups was demonstrated with use of all three novel visual parameters, the global rating scale, and motion analysis (p < 0.05). There were strong and highly significant correlations (p < 0.0001) between each of the novel parameters and the previously validated skill assessment methods., Conclusions: This study demonstrates the construct validity of three novel visual parameters for objectively assessing arthroscopic performance. These parameters are simple, can be used easily in the operating room, and are strongly correlated with current validated methods of technical skill assessment.

Objective: The aim of this study is to present a case of superior oblique muscle dysfunction after a frontal sinus mini-trephine., Methods: This is a case report of an 18-year-old woman where a mini-trephination approach and endoscope were used to open and marsupialize a symptomatic, opacified type IV cell within the left frontal sinus. After surgery, the patient developed a persisting diplopia; a left superior oblique muscle palsy was diagnosed. Nine cadaveric dissections of the trochlea were undertaken to clarify mechanisms for potential trochlear damage., Results: Cadaveric dissection reveals that the trochlea is more than a simple pulley; it is a complex structure in close proximity to the orbital rim. The superior oblique tendon telescopes and is surrounded by a vascular sheath that could be easily traumatized., Conclusion: Damage to the trochlea could occur, as the periosteum is elevated from bone or during healing. Alternatively, prolonged traction on soft tissue near the trochlea could cause swelling of the vascular sheath, fibrosis, and hypomobility of the superior oblique tendon. Careful siting of the incision for external frontal sinus surgery as well as careful retraction of skin flaps and periosteal elevation are all techniques used, which should reduce the risk of damage to the trochlea., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Significant changes in the voice occur after the age of 50 years. Changes in the structure of the vocal fold (VF) can interfere with the voice. The aim of this study is to investigate the structure of the VF of elderly people that may contribute to the tendency of the human voice to deteriorate. Larynges were obtained from eight embalmed cadavers aged 72-98 years. The middle portion of each vocal fold was removed and placed in 4% buffered formalin. Tissue blocks were then processed and embedded in wax. Four to six micron coronal sections were cut and stained with Haematoxylin and Eosin (H&E), Masson's Trichrome (MTS), Elastin van Gieson (EVG), Herovici (HERO), picrosirius and CD31 immunohistochemical marker in order to study the collagen fibers, elastic fibers and microvasculature of the VF. The maturity of collagen fibers within the VF were noted to increase from the superficial to the deep layer of the lamina propria (LP). Contrary to current literature, the amount of elastic fibers was sparse in the superficial layer of the LP in the vocal tissue of elderly cadavers. Numerous cross-sectioned blood vessels were seen in the lamina propria near the free edge, and near the superior and inferior surfaces of the VF. The presence of lymphatic vessels was confirmed in the VF of elderly subjects. This study revealed that the collagenous component of the deep layer of the VF LP was made up of mature fibers whilst immature collagen fibers made up the superficial layer of the LP. There was a notable scarcity of elastic fibers in the superficial layer of the LP. Lymphatics were seen and were orientated differently in the geriatric vocal folds., (Copyright © 2011 Wiley-Liss, Inc.)

Objective: The purpose of this study was to examine whether different techniques used for antegrade cerebral perfusion could account for variation in the perfusion adequacy of the brain and spinal cord., Methods: Selected vessels were ligated in 30 rats, recreating a selection of approaches used in aortic arch surgery for patients undergoing circulatory arrest with antegrade cerebral perfusion. Filling of spinal and cerebral vessels was mapped after cannulation and perfusion with E20, gelatin/India ink, or buffered saline/India ink. Three clinical approaches were replicated: unilateral perfusion, bilateral perfusion, and bilateral perfusion with additional left subclavian artery perfusion. Filling of the spinal arteries via the common carotid arteries or the subclavian arteries alone was examined. Penetration of the marker was analyzed histologically., Results: The control experiments achieved maximal arterial filling of both brain and spinal cord at gross and microscopic levels. Unilateral and bilateral antegrade cerebral perfusion provided comprehensive arterial filling of all cerebral vessels with all vascular markers. In contrast, only bilateral antegrade cerebral perfusion provided complete spinal cord perfusion with all markers. Unilateral antegrade cerebral perfusion with a viscous marker resulted in significantly reduced spinal cord arterial filling. Examination of the relative importance of either both common carotid arteries alone or both subclavian arteries alone, in terms of their adequacy of subsequent arterial filling of the spinal cord, showed severe impairment of spinal cord perfusion with either technique. Thus perfusion of both common carotid arteries resulted in only the proximal 30% of the spinal cord arteries being filled, whereas perfusion of both subclavian arteries resulted in only the proximal 40% of the spinal cord arteries being filled., Conclusions: Approaches to antegrade cerebral perfusion using the brachiocephalic and left common carotid arteries together gave good perfusion of both the brain and the spinal cord. Brachiocephalic perfusion alone gave good cerebral perfusion but showed some significant limitation in spinal cord perfusion with one vascular marker. Complete spinal cord perfusion with all markers under conditions of antegrade cerebral perfusion required some contribution from both the carotid system and the subclavian system together. Selected perfusion of either system alone was very inadequate for spinal cord perfusion., (Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Background: The variations in the anatomy of the external branch of the superior laryngeal nerve (EBSLN) are generally classified according to the relationship of the nerve to the superior thyroid artery, or the superior pole of the thyroid. Both artery and superior pole are themselves variable landmarks, and therefore are not consistent between subjects. We sought to examine EBSLN anatomy in relation to alternate, more consistent surgical landmarks., Methods: Fifteen hemi-larynges from 20 embalmed human cadavers were dissected anatomically. Each nerve was categorized using established classification systems, and terminal branching patterns were also noted. Nerve location was recorded in relation to three different constant anatomical structures: the laryngeal prominence, midline junction of the cricothyroid muscles and ipsilateral cricothyroid joint., Results: All cadavers were of European descent. The EBSLN had two branches to the cricothyroid muscle in 34% of cases. The EBSLN anatomical types found were mainly Cernea type 1 (80%), with 7% type 2a and 13% type Ni. An EBSLN was more likely to lie in an 'at risk' location if the subject was less than 160 cm tall. The EBSLN entered the crico-thyroid muscle at a median distance of 14 mm lateral from the laryngeal prominence and 8 mm inferiorly. The median distance from the medial-most point of the cricothyroid muscle junction was 14 mm laterally and 14 mm superiorly, and from the cricothyroid joint the entry lay a median distance of 10 mm superiorly and 11 mm medially., Conclusions: The variability of EBSLN anatomy is again evident, as is the need for careful and knowledgeable surgical technique. New surgical landmarks for the relations of the insertion of the EBSLN reveal a deployment range for each, but one of more of these landmarks may prove useful in thyroid surgery., (© 2010 The Authors. ANZ Journal of Surgery © 2010 Royal Australasian College of Surgeons.)

The aim of this study was to obtain detailed information regarding the three-dimensional structure of the gastro-oesophageal region, and, in particular, the fiber orientation of the different muscle layers of the junction. This was achieved by a study of an en bloc resection of the gastro-oesophageal junction (GOJ) harvested from a human cadaver. The excised tissue block was suspended in a cage to preserve anatomical relationships, fixed in formalin and embedded in wax. The tissue block was then processed by a custom-built extended-volume imaging system to obtain the microstructural information using a digital camera which acquires images at a resolution of 8.2 microm/pixel. The top surface of the tissue block was sequentially stained and imaged. At each step, the imaged surface was milled off at a depth of 50 microm. The processing of the tissue block resulted in 650 images covering a length of 32.25 mm of the GOJ. Structures, including the different muscle and fascial layers, were then traced out from the cross-sectional images using color thresholding. The traced regions were then aligned and assembled to provide a three-dimensional representation of the GOJ. The result is the detailed three-dimensional microstructural anatomy of the GOJ represented in a new way. The next stage will be to integrate key physiological events, including peristalsis and relaxation, into this model using mathematical modeling to allow accurate visual tools for training health professionals and patients., (2010 Wiley-Liss, Inc.)

This study elucidates the structure of the anal sphincter complex (ASC) and correlates the individual layers, namely the external anal sphincter (EAS), conjoint longitudinal muscle (CLM) and internal anal sphincter (IAS), with their ultrasonographic images. Eighteen male cadavers, with an average age of 72 years (range 62-82 years), were used in this study. Multiple methods were used including gross dissection, coronal and axial sheet plastination, different histological staining techniques and endoanal sonography. The EAS was a continuous layer but with different relations, an upper part (corresponding to the deep and superficial parts in the traditional description) and a lower (subcutaneous) part that was located distal to the IAS, and was the only muscle encircling the anal orifice below the IAS. The CLM was a fibro-fatty-muscular layer occupying the intersphincteric space and was continuous superiorly with the longitudinal muscle layer of the rectum. In its middle and lower parts it consisted of collagen and elastic fibres with fatty tissue filling the spaces between the fibrous septa. The IAS was a markedly thickened extension of the terminal circular smooth muscle layer of the rectum and it terminated proximal to the lower part of the EAS. On endoanal sonography, the EAS appeared as an irregular hyperechoic band; CLM was poorly represented by a thin irregular hyperechoic line and IAS was represented by a hypoechoic band. Data on the measurements of the thickness of the ASC layers are presented and vary between dissection and sonographic imaging. The layers of the ASC were precisely identified in situ, in sections, in isolated dissected specimens and the same structures were correlated with their sonographic appearance. The results of the measurements of ASC components in this study on male cadavers were variable, suggesting that these should be used with caution in diagnostic and management settings.