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β-cyclodextrin and alginate polymers have been extensively investigated for their use in drug delivery systems. β-Cyclodextrin-alginate nanoparticles (CD/Alg) as an innovative drug carrier was the preapared by ionic chelation method. Methotrexate (MTX) as model drug was loaded onto the β-CD/Alg nanoparticles to form MTX-CD/Alg nanocomposites, via ionic interactions. The study was to investigate the changes in independent variables (concentration of CD, Alg and CaCl2) loading efficiency and particle size using 4-levels of CD, 5-levels of Alg and 4-levels of CaCl2. The Optimum nanocomposite has %LE (58.1% and particle size (213 nm). The prepared nanocomposites were chrecterized by powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR), a thermogravimetric analysis (TGA) and a release study. FTIR analysis displayed the drug into nanocomposites. The XRD pattern of MTX-β-CD/Ag nanocomposite suggested a peak at 2θ = 44.6° with the amorphous properties. A novel MTX-CD/Alg nanocomposites was developed. Optimized, characterized, and release studied was performed. These nanocomposites will be prmosing by delivering the drug in powder form. [ABSTRACT FROM AUTHOR]

Mothanna Sadiq Al-Qubaisi,1 Abdullah Rasedee,1,2 Moayad Husein Flaifel,3 Sahrim Hj Ahmad,3 Samer Hussein-Al-Ali,1 Mohd Zobir Hussein,4 Zulkarnain Zainal,4 Fatah H Alhassan,4 Yun H Taufiq-Yap,4 Eltayeb EM Eid,5 Ismail Adam Arbab,1 Bandar A Al-Asbahi,3 Thomas J Webster,6,7 Mohamed Ezzat El Zowalaty1,8,9 1Institute of Bioscience, 2Faculty of Veterinary Medicine, Universiti Putra Malaysia, 3Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 4Faculty of Science, Universiti Putra Malaysia, Selangor, Malaysia; 5College of Pharmacy, Qassim University, Buraidah, Saudi Arabia; 6Department of Chemical Engineering and Program in Bioengineering, Northeastern University, Boston, MA, USA; 7Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi Arabia; 8Faculty of Pharmacy, Zagazig University, Zagazig, Egypt; 9Faculty of Public Health and Tropical Medicine, Jazan University, Jazan, Saudi Arabia Abstract: 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. Keywords: NiZn ferrite nanoparticles, cancer cells, reactive oxygen species, cytochrome C, mitochondrial membrane potential, p53

Mothanna Sadiq Al-Qubaisi,1 Abdullah Rasedee,1,2 Moayad Husein Flaifel,5 Sahrim HJ Ahmad,5 Samer Hussein-Al-Ali,1 Mohd Zobir Hussein,3 Eltayeb EM Eid,6 Zulkarnain Zainal,3 Mohd Saeed,1 Muna Ilowefah,4 Sharida Fakurazi,1 Norhaszalina Mohd Isa,1 Mohamed Ezzat El Zowalaty1,7 1Institute of Bioscience, 2Faculty of Veterinary Medicine, 3Department of Chemistry, Faculty of Science, 4Faculty of Food Science and Technology, Universiti Putra Malaysia, Selangor, Malaysia; 5School of Applied Physics, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Selangor, Malaysia; 6College of Pharmacy, Qassim University, Buraidah, Saudi Arabia; 7Faculty of Pharmacy, Zagazig University, Ash Sharqiyah, Egypt Abstract: 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. Keywords: NiZn ferrite nanoparticles, cancer cells lines, anticancer, apoptosis

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.)

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).)

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.)

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.)

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.)

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.)

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.

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.

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.

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.)

A band of fascial thickening, termed the iliopubic tract, lies on the posterior aspect of the inguinal region and has been described in the surgical literature as playing an important role during herniorraphy. This study was undertaken to examine the gross and microscopic anatomy of the iliopubic tract in 12 cadavers. The results confirmed that the iliopubic tract can be readily identified as a thickening of the transversalis fascia running deep and parallel to the inguinal ligament. It attaches to the superomedial part of the pubic bone medially, but laterally its fibres fan out within the fascia transversalis and fascia iliaca without bony attachment to the iliac spines. In contrast to the inguinal ligament, the histological analysis of the iliopubic tract shows a high elastin to collagen ratio. The functional significance of this structure merits further study, but there is no doubt that it is important in many approaches to inguinal herniorraphy. For this reason it is considered that the iliopubic tract deserves greater emphasis in the anatomy teaching of the inguinal region.

The role of adult astrocytes in the removal of cell debris and foreign particles following injury to the brain is controversial. This study was undertaken to elucidate the response of adult astrocytes to needle injury of the rat cerebral cortex, using a suspension of colloidal carbon as a marker for phagocytosis. Either a single or 2 successive injections of colloidal carbon suspension were made into the cerebral cortex. The animals were allowed to survive for periods of from 1 to 30 d. Unequivocal involvement of astrocytes in the removal of carbon particles was evident only in those brains which had been subjected to 2 successive injections of carbon. The particles were located in membrane-bound vacuoles and were subsequently sequestered in lysosomes. Carbon-containing astrocytes were observed in the immediate vicinity of the lesion, in the adjacent parenchyma, around blood vessels and abutting carbon-containing macrophages. This study demonstrates that adult astrocytes are involved in phagocytosis, but only as a second line of defence. The possible significance of carbon-laden astrocytes further away from the site of the lesion is discussed.

1. The morphology of neurons in the dentate gyrus of the adult human brain was analyzed with two variants of Golgi technique. 2. About 20 neuronal types and subtypes were observed in the dentate gyrus of the adult human, several of which has not previously been described in the human. The human dentate gyrus harbors 4 types of neurons in the molecular layer, 3 types within the granule cell layer, and at least 10 types in the hilus. 3. Compared to the granule neurons in the rat brain, human granule neurons show a much greater variability. Many of these human neurons have basal dendrites and/or axonal spines. Also, there are significant differences among these neurons regarding the density of their dendritic trees and dendritic spines. In contrast to the rat, human hilar neurons with complex spines have complex spines not only on their dendrites but also on their cell bodies. 4. This study opens the door for further morphological studies involving specific diseases such as Alzheimer's disease and epilepsy.

A stab wound was produced in the adult rat cerebral cortex, and the progress of enzyme cytochemistry of phagocytosis was studied over 450 days. Light- and electron-microscopic observations were made to establish the origin of high acid phosphatase activity commonly seen at the site of brain lesions. Cells with phagocytic potential became differentiated and activated by the presence of degenerating neurons. The Golgi-lysosomal system of the phagocytes became elaborated, as evidenced by thiamine pyrophosphatase and acid phosphatase activities, the synthesis of acid phosphatase was increased, and the enzyme then secreted into the digestive vacuoles containing dead cells to be digested. Progress of the digestive process resulted in the accumulation of large amounts of acid phosphatase reaction product within the digestive vacuoles. The results showed that the phagocytes were the only detectable source of increased acid phosphatase activity at the site of injury in the cerebral cortex. In contrast to the phagocytes, newly formed multi-nucleated giant cells exhibited weak acid phosphatase, and intense cytochrome oxidase activities, the difference between the two cells reflecting the functional characteristics of each.