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Background: Alzheimer's disease (AD) is a growing public health concern, yet misconceptions about the condition are common. This study assessed awareness and social perceptions of AD in Jazan., Methods: A cross-sectional survey of 925 adults was conducted. Knowledge was assessed using a 30-item Alzheimer's Disease Knowledge Scale (ADKS). Social perceptions were evaluated using a 10-item questionnaire., Results: Many had misconceptions about AD epidemiology, causes, management, and care. The mean ADKS score was 8.89 ± 5.17 out of 30. Knowledge was poorest for symptoms, risk factors, treatment, caregiving, and life impact. Knowledge was highest in those aged >45 years (p = 0.018), in those with income > 15K SR (p = 0.004), in retired individuals (p = 0.023), and in those who learned about AD from books (p = 0.001), healthcare professionals (p = 0.001), or had an affected relative (p = 0.001). However, knowledge was low across all domains, averaging only 29% correct answers. Most respondents held positive social perceptions, yet sizable minorities saw isolation, legal intervention, and institutionalization as appropriate. Additionally, a portion of respondents associated stigma with individuals affected by AD and expressed a sense of burden associated with the condition., Conclusions: There are substantial knowledge gaps and some stigmatizing attitudes about AD in Jazan. Awareness regarding the causes, diagnosis, and management of AD was low. Misconceptions exist that AD only affects older people. Improved public education, especially for higher-risk groups, is needed to address misconceptions and promote social inclusion for those with dementia. Healthcare professionals can play a crucial role., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Hakami et al.)

This study addressed the challenge of accurately detecting mycotoxins in herbs and spices, which have gained popularity as alternative medicines but pose health risks due to potential contamination. We used a competitive direct ELISA kit (Art No. 8610), Veratox for Ochratoxin, to quantify Ochratoxin A in the herb and spice samples. The samples were first prepared using solid-liquid extraction with 70% methanol. The resulting filtrate was then subjected to ELISA analysis. The results of the analysis were then further analyzed using principal component analysis (PCA). In this study, PCA was used to classify the concentration levels of Ochratoxin A based on various factors, such as the packaging type, country of origin, shelf life, and sample weight. The limits of detection (LOD) and quantification (LOQ) values indicate the lowest amount of Ochratoxin A that can be detected and quantified, respectively, with high accuracy and precision. The range of the LOD and LOQ values (0.43-0.58 µg/kg and 1.45-1.95 µg/kg, respectively) suggests that the method used was capable of detecting and quantifying Ochratoxin A in the herb and spice samples at different concentrations with a high degree of accuracy and precision. These results suggest that while most of the samples (73.33%) were below the maximum residue limit (MRL) for Ochratoxin A, a significant number of samples (26.67%) had concentrations of Ochratoxin A that were higher than the MRL. This highlights the importance of monitoring Ochratoxin A in herb and spice samples and ensuring the products are safe for consumption., Competing Interests: The authors declare no conflict of interest., (©2023 JOURNAL of MEDICINE and LIFE.)

Background: Mefenamic acid (MFA), a common analgesic, causes central nervous system (CNS) toxicity at high doses with a proposed activity on the Gamma-aminobutyric acid (GABA) system. However, it remains unknown whether flumazenil (FMZ), a GABA type A receptor (GABAAR) antagonist, can reverse MFA toxicity., Methods: The behavioral and neurophysiological effects of MFA were investigated in mice with and without FMZ pre-treatment. The elevated zero maze (EZM) and marble burying tests were used to assess anxiety-like behaviors and burying activities, respectively. The standard bar test was used to evaluate catalepsy, while the actophotometer test was used to measure locomotor activity. Seizure intensity was scored, and fatalities were counted., Results: Without FMZ pre-treatment, MFA induced behavioral and neurophysiological effects in a dose-dependent manner as follows: At a dose of 20 mg/kg, i.p, MFA-treated mice exhibited anxiety-like behaviors, which was determined by a significant increase in the time spent in the closed areas and a significant decrease in the number of entries to the open areas of the EZM apparatus. These mice also showed a significant decrease in the burying activity, manifested as a significant decrease in the number of buried marbles. At 40 mg/kg, i.p., MFA-treated mice showed catalepsy that was associated with a significant decrease in locomotor activity. At a dose of 80 mg/kg, i.p., mice developed fatal tonic-clonic seizures (seizure score = 4). Pre-treatment with FMZ (5 mg/kg, i.p.) significantly reversed the anxiety-like behaviors and restored marble-burying activity. Additionally, FMZ prevented catalepsy, significantly restored locomotor activity, reduced seizure intensity (seizure score = 0.3) and significantly reduced mortalities., Conclusions: The present study's findings indicate that activation of the GABAAR is involved in the CNS toxicity of MFA, and FMZ reverses MFA toxicity by interfering with this receptor., Competing Interests: The authors declare no conflict of interest., (© 2023 The Author(s). Published by IMR Press.)

This paper documents changes in infant mortality (IM) rates in São Paulo, Brazil, between 2003 and 2013 and examines the association among neighborhood characteristics and IM. We investigate the extent to which increased use of health care services and improvements in economic and social conditions are associated with reductions in IM. Using data from the Brazilian Census and the São Paulo Secretaria Municipal da Saúde/SMS, we conducted a longitudinal analysis of panel data in all 96 districts of São Paulo for every year between 2003 and 2013. Our regression model includes district level measures that reflect economic, health care and social determinants of IM. We find that investments in health care have contributed to lower IM rates in the city, but the direct effect of increased spending is most evident for people living in São Paulo's middle- and high-income neighborhoods. Improvements in social conditions were more strongly associated with IM declines than increases in the use of health care among São Paulo's low-income neighborhoods. To reduce health inequalities, policies should target benefits to lower-income neighborhoods. Subsequent research should document the consequences of recent changes in Brazil's economic capacity and commitment to public health spending for population health.

Objective: Human exposure to multiple xenobiotics, over various developmental windows, results in adverse health effects arising from these concomitant exposures. Humans are widely exposed to bisphenol A, and acetaminophen is the most commonly used over-the-counter drug worldwide. Bisphenol A is a well-recognized male reproductive toxicant, and increasing evidence suggests that acetaminophen is also detrimental to the male reproductive system. The recent recognition of male reproductive system dysfunction in conditions of suboptimal reproductive outcomes makes it crucial to investigate the contributions of toxicant exposures to infertility and sub-fertility. We aimed to identify toxicity in the male reproductive system at the mitochondrial level in response to co-exposure to bisphenol A and acetaminophen, and we investigated whether melatonin ameliorated this toxicity., Methods: Male Wistar rats were divided into six groups (n=10 each): a control group and groups that received melatonin, bisphenol A, acetaminophen, bisphenol A and acetaminophen, and bisphenol A and acetaminophen with melatonin treatment., Results: Significantly higher lipid peroxidation was observed in the testicular mitochondria and sperm in the treatment groups than in the control group. Levels of glutathione and the activities of catalase, glutathione peroxidase, glutathione reductase, and manganese superoxide dismutase decreased significantly in response to the toxicant treatments. Likewise, the toxicant treatments significantly decreased the sperm count and motility, while significantly increasing sperm mortality. Melatonin mitigated the adverse effects of bisphenol A and acetaminophen., Conclusion: Co-exposure to bisphenol A and acetaminophen elevated oxidative stress in the testicular mitochondria, and this effect was alleviated by melatonin.

Serial reaction time tasks, in which subjects have to match a target to a cue, are used to explore whether non-human animals have multiple memory systems. Predictable sub-sequences embedded in the sequence of cues are responded to faster, demonstrating incidental learning, often considered implicit. Here, we used the serial implicit learning task (SILT) to determine whether rats' memory shows similar effects. In SILT, subjects must nose-poke into a sequence of two lit apertures, S1 and S2. Some S1 are always followed by the same S2, creating predictable sequences (PS). Across groups, we varied the proportion of PS trials, from 10 to 80%, and show that rats with more PS experience do better on them than on unpredictable sequences, and better than rats with less experience. We then introduced test trials in which no S2 was cued. Rats with more PS experience did better on test trials. Finally, we reversed some sequences (from predictable to unpredictable and vice versa) and changed others. We find that rats with more PS experience perseverate on old (now incorrect) responses more than those with less PS experience. Overall, we find a discontinuity in performance as the proportion of PS increases, suggesting a switch in behavioral strategies or memory systems, which we confirm using a Process Dissociation Procedure analysis. Our data suggest that rats have at least two distinct memory systems, one of which appears to be analogous to human implicit memory and is differentially activated by varying the proportion of PS in our task., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The elevated plus maze (EPM) and the marble burying (MB) tests are common behavioral tests used for behavioral phenotyping in mouse models for neurodevelopmental disorders. However, the behavioral effects of maternal separation (MS), a standard paradigm for early life stress in animals, in both the EPM and MB tests remain incompletely known., Objectives: This study aimed to investigate the behavioral effects of prolonged MS in the offspring of mice using the EPM and MB tests., Methods: Male BALB/c mice were isolated from their mothers for 4 h each day during the first 30 days after birth. On day 50 postnatal, groups of separated and non-separated mice ( n = 18/each group) were subjected to the EPM and MB tests for comparative behavioral evaluations. In addition, the locomotor activity of mice was evaluated using the actophotometer test., Results: The findings of the EPM test revealed that separated mice exhibited anxiolytic-like behaviors, as evidenced by a significant increase in the latency to closed arms and the time spent in the open arms compared with non-separated mice. Separated mice also showed compulsive burying activity in the MB test, as determined by a significant increase in the number of buried marbles. The results of the actophotometer test did not show any significant change in locomotor activity., Conclusions: Prolonged MS caused the adult offspring of mice to exhibit a decrease in anxiety state and increased compulsive burying activity, which were not associated with a change in locomotor activity. Further investigations with validated tests are needed to support these findings.

Background: Fibromyalgia is a chronic disease with a high burden. We aim to be the first to investigate the prevalence of fibromyalgia (FM) in Syria and assess its risk factors., Methods: A self-reported questionnaire was distributed to the public to identify fibromyalgia patients using the American College of Rheumatology (ACR) 2010 modified criteria. Identified cases were matched using age with controls free from rheumatic disorders that were randomly sampled from the same population., Results: Out of 2966 participants, 350 (11.8%) satisfied the diagnostic criteria. Of these, only 29 (8.2%) were previously diagnosed by a physician, 239 (68.3%) were females, and 69 (19.71%) were diagnosed with depression. Female sex (OR = 1.31), diagnosis of major depressive disorder (OR = 2.62), irritable bowel syndrome (OR = 1.8), and Restless legs syndrome (OR = 1.72) were associated with a higher likelihood of fibromyalgia., Conclusion: Our study revealed one of the highest prevalence rates of fibromyalgia ever reported in the general population. Efforts must be intensified to increase awareness about this disease in Syrian society as well as among healthcare providers., (© 2022. The Author(s).)

Medulloblastoma (MB) comprises a group of heterogeneous paediatric embryonal neoplasms of the hindbrain with strong links to early development of the hindbrain 1-4 . Mutations that activate Sonic hedgehog signalling lead to Sonic hedgehog MB in the upper rhombic lip (RL) granule cell lineage 5-8 . By contrast, mutations that activate WNT signalling lead to WNT MB in the lower RL 9,10 . However, little is known about the more commonly occurring group 4 (G4) MB, which is thought to arise in the unipolar brush cell lineage 3,4 . Here we demonstrate that somatic mutations that cause G4 MB converge on the core binding factor alpha (CBFA) complex and mutually exclusive alterations that affect CBFA2T2, CBFA2T3, PRDM6, UTX and OTX2. CBFA2T2 is expressed early in the progenitor cells of the cerebellar RL subventricular zone in Homo sapiens, and G4 MB transcriptionally resembles these progenitors but are stalled in developmental time. Knockdown of OTX2 in model systems relieves this differentiation blockade, which allows MB cells to spontaneously proceed along normal developmental differentiation trajectories. The specific nature of the split human RL, which is destined to generate most of the neurons in the human brain, and its high level of susceptible EOMES + KI67 + unipolar brush cell progenitor cells probably predisposes our species to the development of G4 MB., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background Heart murmurs are defined as whooshing or swishing sounds, unlike the normal lub-dub sounds detected by physicians while using a stethoscope. They usually develop due to numerous pathologies, with congenital defects accounting for the majority of pediatric murmurs. Few studies have addressed the difference in auscultating skills between senior and junior healthcare providers. Therefore, this study aims to collect local data on this topic as well as identify the gap between experienced and inexperienced providers in their ability to accurately detect heart murmurs. Methodology This study utilizes a quantitative retrospective design to collect data from King Abdulaziz Medical City and King Faisal Cardiac Centre, Saudi Arabia, from October 1, 2018, to September 30, 2019. The medical records of 292 pediatric patients, who were 14 years of age or below according to the centers' aging system, were collected from the Hospital Information System (BESTCare). Subsequently, it was determined whether a senior (R3-R4 residents and above) or a junior (R1-R2 residents and interns) healthcare provider ordered an echocardiogram (ECHO). Finally, using the centers' imaging system (Xcelera) the exact reason for referral, heart murmurs in the case of this study, was obtained, as well as whether a pathologic cause of a murmur was seen in the ECHO image. By obtaining the aforementioned data, the accuracy of each referral was analyzed using statistical analysis software. Results ECHO results were categorized into positive and negative outcomes depending on the presence of a structural heart defect, patent foramen ovale (PFO) was considered negative as it causes innocent murmurs. The majority of positive results were atrial septal defects, patent ductus arteriosus, and ventricular septal defects. The majority of negative results were either a structurally normal heart or PFO, which a great number of providers ordered an ECHO for. The Pearson score p-value using the chi-square test was 0.432, leading to the conclusion that junior and senior providers had a similar accuracy of referrals during the study period. Conclusions Junior healthcare providers display sufficient knowledge of heart murmur auscultation skills similar to senior healthcare providers during the study period. However, because the data only included two local centers with a limited sample and the absence of further local research on this topic, it is necessary to conduct studies of a larger scope on this topic., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Waggass et al.)

2-(4-Chlorophenyl)-5-benzoxazoleacetic acid (CBA) and its ester, methyl-2-(4-chloro-phenyl)-5-benzoxazoleacetate (MCBA), were synthesized, and their structures were confirmed by 1 HNMR, IR, and mass spectrophotometry. The anti-psoriatic activities of CBA and MCBA were tested using an imiquimod (IMQ)-induced psoriatic mouse model, in which mice were treated both topically (1% w/w ) and orally (125 mg/kg) for 14 days. The erythema intensity, thickness, and desquamation of psoriasis were scored by calculating the psoriasis area severity index (PASI). The study also included the determination of histopathological alterations in the skin tissues of treated mice. Topical and oral administration of CBA and MCBA led to a reduction in erythema intensity, thickness, and desquamation, which was demonstrated by a significant decrease in the PASI value. In addition, skin tissues of mice treated with CBA and MCBA showed less evidence of psoriatic alterations, such as hyperkeratosis, parakeratosis, scale crust, edema, psoriasiform, and hyperplasia. After administration of either topical or oral dosing, the anti-psoriatic effects were found to be stronger in MCBA-treated than in CBA-treated mice. These effects were comparable to those produced by Clobetasol propionate, the reference drug. This drug discovery could be translated into a potential new drug for future clinical use in psoriasis treatment.

Background The coronavirus disease 2019 (COVID-19) pandemic has negatively affected many aspects of daily life. In Saudi Arabia, many studies, using a range of assessment approaches, have examined how the pandemic has affected the mental health of both the general public and healthcare workers. However, to develop effective public-health initiatives for such crisis events, it would also be relevant to determine the pandemic's impact on the behavioral, emotional, and social lives of Saudi children. Objective To assess, among Saudi children aged 3-15 years, the behavioral, emotional, and social changes that have occurred in their daily lives due to the COVID-19 pandemic. Materials and methods This study featured a cross-sectional design. Potential participants were approached through the most popular social media in Saudi Arabia, and the final sample size was 651 parents. As, at the time of data collection, the members of the Saudi public were requested to avoid face-to-face meetings where possible, a well-designed electronic questionnaire featuring closed-ended questions was used. Results Descriptive statistics showed that the mean age of the parents was 29±7 years (range: 20-60 years); over half (58%) were female. During the COVID-19 outbreak, one-third of children had asked to sleep in their parents' beds. Furthermore, approximately 30% of children demonstrated increased irritability and mood swings when compared with the period before the pandemic. Concerning adaptive social behaviors, during the pandemic, 22% of children appeared calmer and 14% of children seemed more thoughtful. Our study reports more screen time, less physical activity, and reduced sleep time among children compared with the pre-pandemic period. Conclusion The COVID-19 pandemic has psychologically affected children. The present results highlight the need to reduce this psychological burden by enhancing children's emotional resilience and involving parents in health-promotion programs aimed at mitigating the negative impacts of such public-health crises., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Almugti et al.)

Background and Objectives: We assessed longitudinal changes in CSF microRNAs (miRNAs) in patients with moderately severe Parkinson disease., Methods: We used next-generation whole-genome miRNA sequencing to determine CSF miRNA expression in 75 patients with Parkinson disease after single random ascending doses of nilotinib and longitudinal miRNA expression after daily nilotinib, 150 and 300 mg, vs placebo for 1 year., Results: Significant changes in the expression of miRNAs that control genes and pathways that regulate angiogenesis, autophagy, and the blood-brain-barrier components, primarily collagen, were observed over 1 year, suggesting impairment of these pathways in Parkinson progression in these patients. Different miRNAs that indicate activation of genes associated with autophagy flux and clearance and angiogenesis were significantly altered in the nilotinib, 300 mg vs 150 mg, or placebo group, and these changes correlated with clinical outcomes. No changes were observed in miRNAs after a single dose of nilotinib vs placebo., Discussion: This study suggests vascular and autophagy defects in Parkinson progression. Nilotinib, 300 mg, reverses these effects via alteration of miRNA expression, suggesting epigenomic changes that may underlie long-term disease-modifying effects., Trial Registration Information: Clinical trial registration number: NCT02954978., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Sequelae after pediatric cranial radiotherapy (CRT) result in long-term changes in brain structure. While past evidence indicates regional differences in brain volume change, it remains unclear how these manifest in the time course of change after CRT. In this study, we spatiotemporally characterized volume losses induced by cranial irradiation in a mouse model, with a dense sampling of measurements over the first week postirradiation. Wild-type mice received whole-brain irradiation (7 Gy) or sham irradiation (0 Gy) at 16 days of age. In vivo magnetic resonance imaging was performed at one time point before, and 2-4 time points postirradiation in each mouse, with a particular focus on sampling during the first week after cranial irradiation. Volume changes across the brain were measured, and the degree and timing of volume loss were quantified across structures from a predefined atlas. Volume measurements across the brain after cranial irradiation revealed a ∼2-day delay in which volume is not significantly altered, after which time volume change proceeds over the course of four days. Volume losses were 3% larger and emerged 40% slower in white matter than in gray matter. Large volume loss was also observed in the ventricles. Differences in the timing and magnitude of volume change between gray and white matter after cranial irradiation were observed. These results suggest differences in the mechanism and/or kinetics underlying the associated radio-response, which may have implications in development., (©2021 by Radiation Research Society. All rights of reproduction in any form reserved.)

Background: Mefenamic acid (MFA), a commonly prescribed non-steroidal anti-inflammatory drug (NSAID), possesses a greater risk of dose-related central nervous system (CNS) toxicity than other NSAIDs. In this study, α-tocopherol and α-tocopherol acetate were selected as prodrug moieties for MFA in an attempt to reduce the CNS toxicity and enhance the therapeutic efficacy., Method: α-tocopherol monoester of MFA (TMMA) and α-tocopherol di-ester of MFA (TDMA) were synthesized by esterification reaction and were subjected to various in vivo characterizations., Results: Masking of the carboxylate group of MFA with the proposed pro-moieties significantly (p<0.05) delayed the onset of tonic-clonic seizure in mice. Besides, the intraperitoneal administration of TMMA and TDMA in mice produced significantly (p<0.05) stronger anti-inflammatory effects in the carrageenan-induced paw edema test and greater anti-nociceptive effect in the acetic acid-induced writhing test than MFA at an equimolar dose of 20 mg/kg. Treatment with TMMA and TDMA caused a significant (p<0.05) inhibition of pain at 1st and 2nd phases of formalin-induced licking test in mice, whereas treatment with MFA inhibited the 2nd phase only. Pretreatment with naloxone and flumazenil significantly (p<0.05) reversed the anti-nociceptive effect of MFA, TMMA and TDMA in the acetic acid-induced writhing test. In addition, treatment with TMMA and TDMA caused significantly (p<0.05) a higher inhibition of pain in the glutamate-induced licking response in mice than MFA., Conclusion: Masking the carboxylate moiety of MFA by α-tocopherol and α-tocopherol acetate has a great potential for reducing CNS toxicity, enhancing the therapeutic efficacy and altering the mode of anti-nociceptive action., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Protein structure prediction is a long-standing unsolved problem in molecular biology that has seen renewed interest with the recent success of deep learning with AlphaFold at CASP13. While developing and evaluating protein structure prediction methods, researchers may want to identify the most similar known structures to their predicted structures. These predicted structures often have low sequence and structure similarity to known structures. We show how RUPEE, a purely geometric protein structure search, is able to identify the structures most similar to structure predictions, regardless of how they vary from known structures, something existing protein structure searches struggle with. RUPEE accomplishes this through the use of a novel linear encoding of protein structures as a sequence of residue descriptors. Using a fast Needleman-Wunsch algorithm, RUPEE is able to perform alignments on the sequences of residue descriptors for every available structure. This is followed by a series of increasingly accurate structure alignments from TM-align alignments initialized with the Needleman-Wunsch residue descriptor alignments to standard TM-align alignments of the final results. By using alignment normalization effectively at each stage, RUPEE also can execute containment searches in addition to full-length searches to identify structural motifs within proteins. We compare the results of RUPEE to the protein structure searches mTM-align, SSM, CATHEDRAL, and VAST using a benchmark derived from the protein structure predictions submitted to CASP13. RUPEE identifies better alignments on average with respect to TM-score as well as scores specific to SSM and CATHEDRAL, Q-score and SSAP-score, respectively., (© 2021 Wiley Periodicals LLC.)

Objectives: Whether to preserve or sacrifice the intercostobrachial nerves (ICBN) is a controversial issue. In this trial, we aim to assess the effects of preservation of the ICBN during axillary dissection for patients with breast cancer in terms of pain score immediately postoperatively and several hours later, need for simple analgesia and narcotics, numbness and arm swelling., Materials and Methods: This is a single-institution, single-surgeon randomized controlled trial where a sample of 48 patients with breast cancer, of various age groups, were allocated randomly to any of the 2; preservation or sacrifice categories. Postoperatively, patients were asked by a physician to fill a predesigned questionnaire to assess the studied items during hospitalization and after discharge., Results: Among the 48 included patients, ICBN was sacrificed in 24 patients; of which 18 patients (75%) developed numbness in the inner aspect of the arm. While in the ICBN preservation group (24 patients) only 6 patients suffered numbness (25%) with a significant P-value of 0.001. Estimated duration of surgery with ICBN preservation was 100±22.02 minutes, while it is significantly shorter in the ICBN sacrifice group (83.48±21.55). However, with regard to other variables of pain, seroma formation, need of simple analgesia and narcotics, hospital admission days and arm swelling, there was no significant difference between the 2 groups., Conclusion: This study can conclude that preservation of ICBN during axillary dissection in patients with breast CA can save these patients' additional suffering from inner arm numbness. That is at the expense of surgery duration, around 20 minutes longer, for the surgeon to take his/her time in carefully dissecting the axilla properly without injuring these ICBN., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: . Ocular injuries constitute a major cause of visual morbidity, and they have a significant socioeconomic impact worldwide. We aimed to document the types and causes of Syrian War related ocular injuries in Damascus, Syria., Methods: . Medical records were retrospectively reviewed to evaluate all patients in Al-Mouwasat University Hospital and Damascus Hospital, whose ocular injuries were caused by war-related activities during the period extending between January of 2016 and December 2017., Results: . 150 eye injuries in 127 patients were reviewed, in which 46 (31%) were bilateral and 87 (58%) were open globe injuries. The leading cause of the observed ocular injuries was improvised explosive devices (IED) [37 eyes (41%)]. The majority of patients presented with an initial best corrected visual acuity (BCVA) of "light perception" (LP) to "hand movement" (HM) [51 eyes (34%)]. Information on the final BCVA was available for 69 injured eyes only, and it was "no light perception" (NLP) in 20 eyes (29%)., Conclusion: . Explosive weaponry is the main culprit in most war-related ocular injuries in Syria. The high incidence of open globe injuries caused many of the cases to be severe in nature. Education on the precautionary measures that protect the eyes such as the use of combat eye protection during wartimes ought to be enforced, so that future ocular injuries can be prevented., Competing Interests: Declaration of Competing Interest None, (Copyright © 2020. Published by Elsevier Ltd.)

Background: Linear scleroderma "en coups de sabre" is a disease that causes scar-like lesions in the forehead and the scalp, and atrophy of the underlying structures. The result is an acute facial asymmetry that can be distressing to affected young adults. Several surgical treatments are available such as free tissue transfer and synthetic fillers., Aims: In this report, we present a rare case of linear scleroderma "en coups de sabre," which was successfully managed with single-stage autologous fat grafting., Patients/methods: The patient was a 17-year-old male who presented with a soft-tissue defect in the left forehead region. Treatment consisted of transferring autologous fat into the defect in a retrograde fashion, as described by Coleman, and overcorrecting the defect to account for fat resorption., Results: At 6 mo postoperatively, the patient had maintained a satisfactory correction of his left forehead and scalp regions with minimal resorption of fat., Conclusion: Autologous fat grafting provides a safe and easy approach for the treatment of linear scleroderma "en coups de sabre". With minimal manipulation of the aspirated fat, combined with overcorrection of the defect, long-term clinically satisfactory results can be obtained., (© 2020 Wiley Periodicals LLC.)

We asked whether pharmacological stimulation of endogenous neural precursor cells (NPCs) may promote cognitive recovery and brain repair, focusing on the drug metformin, in parallel rodent and human studies of radiation injury. In the rodent cranial radiation model, we found that metformin enhanced the recovery of NPCs in the dentate gyrus, with sex-dependent effects on neurogenesis and cognition. A pilot double-blind, placebo-controlled crossover trial was conducted (ClinicalTrials.gov, NCT02040376) in survivors of pediatric brain tumors who had been treated with cranial radiation. Safety, feasibility, cognitive tests and MRI measures of white matter and the hippocampus were evaluated as endpoints. Twenty-four participants consented and were randomly assigned to complete 12-week cycles of metformin (A) and placebo (B) in either an AB or BA sequence with a 10-week washout period at crossover. Blood draws were conducted to monitor safety. Feasibility was assessed as recruitment rate, medication adherence and procedural adherence. Linear mixed modeling was used to examine cognitive and MRI outcomes as a function of cycle, sequence and treatment. We found no clinically relevant safety concerns and no serious adverse events associated with metformin. Sequence effects were observed for all cognitive outcomes in our linear mixed models. For the subset of participants with complete data in cycle 1, metformin was associated with better performance than placebo on tests of declarative and working memory. We present evidence that a clinical trial examining the effects of metformin on cognition and brain structure is feasible in long-term survivors of pediatric brain tumors and that metformin is safe to use and tolerable in this population. This pilot trial was not intended to test the efficacy of metformin for cognitive recovery and brain growth, but the preliminary results are encouraging and warrant further investigation in a large multicenter phase 3 trial.

The goal of this study was to develop and statistically optimize the metronidazole (MET), chitosan (CS) and alginate (Alg) nanoparticles (NP) nanocomposites (MET-CS-AlgNPs) using a (2 1 × 3 1 × 2 1 ) × 3 = 36 full factorial design (FFD) to investigate the effect of chitosan and alginate polymer concentrations and calcium chloride (CaCl 2 ) concentration ondrug loading efficiency(LE), particle size and zeta potential. The concentration of CS, Alg and CaCl 2 were taken as independent variables, while drug loading, particle size and zeta potential were taken as dependent variables. The study showed that the loading efficiency and particle size depend on the CS, Alg and CaCl 2 concentrations, whereas zeta potential depends only on the Alg and CaCl 2 concentrations. The MET-CS-AlgNPs nanocomposites were characterized by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA), scanning electron microscopy (SEM) and in vitro drug release studies. XRD datashowed that the crystalline properties of MET changed to an amorphous-like pattern when the nanocomposites were formed.The XRD pattern of MET-CS-AlgNPs showed reflections at 2θ = 14.2° and 22.1°, indicating that the formation of the nanocompositesprepared at the optimum conditions havea mean diameter of (165±20) nm, with a MET loading of (46.0 ± 2.1)% and a zeta potential of (-9.2 ± 0.5) mV.The FTIR data of MET-CS-AlgNPs showed some bands of MET, such as 3283, 1585 and 1413 cm -1 , confirming the presence of the drug in the MET-CS-AlgNPs nanocomposites. The TGA for the optimized sample of MET-CS-AlgNPs showed a 70.2% weight loss compared to 55.3% for CS-AlgNPs, and the difference is due to the incorporation of MET in the CS-AlgNPs for the formation of MET-CS-AlgNPs nanocomposites. The release of MET from the nanocomposite showed sustained-release properties, indicating the presence of an interaction between MET and the polymer. The nanocomposite shows a smooth surface and spherical shape. The release profile of MET from its MET-CS-AlgNPs nanocomposites was found to be governed by the second kinetic model ( R 2 between 0.956-0.990) with more than 90% release during the first 50 h, which suggests that the release of the MET drug can be extended or prolonged via the nanocomposite formulation.

Olive growing in Lebanon plays an important role at both a social and economic level. Nevertheless, the quality of olive oil produced in the country is rarely addressed. In this study, oil content, fatty acid, and phenolic profiles were studied along four different ripening stages for 11 varieties of olives, including two clones of the local variety "Baladi," in addition to nine foreign varieties ("Ascolana Tenera," "Bella di Cerignola," "Itrana," "Jabaa," "Kalamata," "Nabali," "Salonenque," "Sigoise," and "Tanche"). Oil content was determined using the Soxhlet method and Abencor system. Fatty acid composition was determined using a GC-FID, total phenols using spectrophotometry, and the phenolic profile using HPLC-DAD. Results showed that variety, fruit ripening and their interaction have a significant effect on the overall studied oil parameters. Among the studied varieties, "Kalamata" presented the higher oil content on dry matter (OCDM = 48.24%), "Baladi 1" the highest oil content on humid matter (OCHM = 27.86%), and "Tanche" the highest oil industrial yield (OIY = 19.44%). While "Tanche" recorded the highest C18:1 (71.75%), "Ascolana Tenera" showed the highest total phenols (TP = 539 mg GAE/Kg of oil), "Salonenque" the highest oleacein (121.57 mg/Kg), and "Itrana" the highest oleocanthal contents (317.68 mg/Kg). On the other hand, oil content together with C18:2 and C18:0 increased along ripening while C18:1, total phenols and the main individual phenols decreased. Although preliminary, this study highlights the good quality of olive oil produced from both local and foreign varieties growing in Lebanon and encourages further investigations on the characterization and authentication of Lebanese olive oil.

Given the close relationship between protein structure and function, protein structure searches have long played an established role in bioinformatics. Despite their maturity, existing protein structure searches either use simplifying assumptions or compromise between fast response times and quality of results. These limitations can prevent the easy and efficient exploration of relationships between protein structures, which is the norm in other areas of inquiry. To address these limitations we have developed RUPEE, a fast and accurate purely geometric structure search combining techniques from information retrieval and big data with a novel approach to encoding sequences of torsion angles. Comparing our results to the output of mTM, SSM, and the CATHEDRAL structural scan, it is clear that RUPEE has set a new bar for purely geometric big data approaches to protein structure searches. RUPEE in top-aligned mode produces equal or better results than the best available protein structure searches, and RUPEE in fast mode demonstrates the fastest response times coupled with high quality results. The RUPEE protein structure search is available at https://ayoubresearch.com. Code and data are available at https://github.com/rayoub/rupee., Competing Interests: The authors have declared that no competing interests exist.

Aim: The aim of this study was to perform an audit of the use of statins in Australian pediatric hospitals., Methods: A retrospective audit of patients prescribed statins during a visit to a pediatric hospital, as in- or outpatients, was performed in four major children's hospitals in three Australian states. Patients were identified through hospital pharmacy dispensing records. Statin use (dose, type) as well as medical history was recorded., Results: A total of 157 patients under the age of 18 were included in the audit. The most common reasons for being prescribed a statin included history of organ transplantation, renal disease and familial hypercholesterolemia (FH). Four statins were prescribed: atorvastatin (n = 77), pravastatin (n = 45), simvastatin (n = 25) and rosuvastatin (n = 10). All statins, apart from rosuvastatin, were used in very young children (1-7 years old). Polypharmacy was common in these patients, including combinations with calcineurin inhibitors and diltiazem, which can increase systemic statin exposure. A small number of very young children were prescribed high doses of statin, based on mg/kg dosing., Conclusions: Statins were prescribed to children younger than suggested by current Australian guidelines, with atorvastatin being the preferred statin of choice. Long-term safety studies on the use of statins in children have only included FH patients so far, who are generally healthy besides their raised lipid levels. Further long-term safety studies are needed to include the more vulnerable transplant and renal patients, identified in this audit as being prescribed statins. This can help formulate guidelines for the safest possible use of this class of drugs in the pediatric setting, including the possibility of weight-based recommendations for younger children.

Mechanical loads play a pivotal role in the growth and maintenance of bone and joints. Although loading can activate anabolic genes and induce bone remodeling, damping is essential for preventing traumatic bone injury and fracture. In this study we investigated the damping capacity of bone, joint tissue, muscle, and skin using a mouse hindlimb model of enhanced loading in conjunction with finite element modeling to model bone curvature. Our hypothesis was that loads were primarily absorbed by the joints and muscle tissue, but that bone also contributed to damping through its compression and natural bending. To test this hypothesis, fresh mouse distal lower limb segments were cyclically loaded in axial compression in sequential bouts, with each subsequent bout having less surrounding tissue. A finite element model was generated to model effects of bone curvature in silico. Two damping-related parameters (phase shift angle and energy loss) were determined from the output of the loading experiments. Interestingly, the experimental results revealed that the knee joint contributed to the largest portion of the damping capacity of the limb, and bone itself accounted for approximately 38% of the total phase shift angle. Computational results showed that normal bone curvature enhanced the damping capacity of the bone by approximately 40%, and the damping effect grew at an accelerated pace as curvature was increased. Although structural curvature reduces critical loads for buckling in beam theory, evolution apparently favors maintaining curvature in the tibia. Histomorphometric analysis of the tibia revealed that in response to axial loading, bone formation was significantly enhanced in the regions that were predicted to receive a curvature-induced bending moment. These results suggest that in addition to bone's compressive damping capacity, surrounding tissues, as well as naturally-occurring bone curvature, also contribute to mechanical damping, which may ultimately affect bone remodeling and bone quality., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Functional neuroimaging (fMRI) studies show activation in mesolimbic circuitry in tasks involving reward processing, like the Monetary Incentive Delay Task (MIDT). In voltammetry studies in animals, mesolimbic dopamine release is associated with reward salience. This study examined the relationship between fMRI activation and magnitude of dopamine release measured with Positron emission tomography study (PET) in the same subjects using MIDT in both modalities to test if fMRI activation is related to dopamine release. Eighteen healthy subjects were scanned with [¹¹C]raclopride PET at baseline and after MIDT. Binding potential (BP(ND)) was derived by equilibrium analysis in striatal subregions and percent change across conditions (∆BP(ND)) was measured. Blood oxygen level dependence (BOLD) signal changes with MIDT were measured during fMRI using voxelwise analysis and ROI analysis and correlated with ∆BP(ND). ∆BP(ND) was not significant in the ventral striatum (VST) but reached significance in the posterior caudate. The fMRI BOLD activation was highest in VST. No significant associations between ∆BP(ND) and change in fMRI BOLD were observed with VST using ROI analysis. Voxelwise analysis showed positive correlation between BOLD activation in anticipation of the highest reward and ∆BP(ND) in VST and precommissural putamen. Our study indicates that endogenous dopamine release in VST is of small magnitude and is related to BOLD signal change during performance of the MIDT in only a few voxels when rewarding and nonrewarding conditions are interspersed. The lack of correlation at the ROI level may be due to the small magnitude of release or to the particular dependence of BOLD on glutamatergic signaling.

Mitochondrial dysfunction subsequent to increased oxidative stress and alterations in energy metabolism is considered to play a role in the development of cardiac hypertrophy and its progression to failure, although the sequence of events remains to be elucidated. This study aimed at characterizing the impact of hypertrophy development on the activity and expression of mitochondrial NADP+-isocitrate dehydrogenase (mNADP+-ICDH), a metabolic enzyme that controls redox and energy status. We expanded on our previous finding of its inactivation through posttranslational modification by the lipid peroxidation product 4-hydroxynonenal (HNE) in 7-wk-old spontaneously hypertensive rat (SHR) hearts before hypertrophy development (Benderdour et al. J Biol Chem 278: 45154-45159, 2003). In this study, we used 7-, 15-, and 30-wk-old SHR and Sprague-Dawley (SD) rats with abdominal aortic coarctation. Compared with age-matched control Wistar-Kyoto (WKY) rats, SHR hearts showed a significant 25% decrease of mNADP+-ICDH activity, which preceded in time 1) the decline in its protein and mRNA expression levels (between 10% and 35%) and 2) the increase in hypertrophy markers. The chronic and persistent loss of mNADP+-ICDH activity in SHR was associated with enhanced tissue accumulation of HNE-mNADP+-ICDH and total HNE-protein adducts at all ages and contrasted with the profile of changes in the activity of other mitochondrial enzymes involved in antioxidant or energy metabolism. Two-way ANOVA of the data also revealed a significant effect of age on most parameters measured in SHR and WKY hearts. The mNADP+-ICDH activity, protein, and mRNA expression were reduced between 25% and 35% in coarctated SD rats and were normalized by treatment of SHR or coarctated SD rats with renin-angiotensin system inhibitors, which prevented or attenuated hypertrophy. Altogether, our data show that cardiac mNADP+-ICDH activity and expression are differentially and sequentially affected in hypertrophy development and, to a lesser extent, with aging. Decreased cardiac mNADP+-ICDH activity, which is attributed at least in part to HNE adduct formation, appears to be a relevant early and persistent marker of mitochondrial oxidative stress-related alterations in hypertrophy development. Potentially, this could also contribute to the aetiology of cardiomyopathy.

Effects of the alpha 2-adrenoceptor agonists xylazine and detomidine on food intake in freely feeding male rats were evaluated. Intraperitoneal (i.p.) injection of xylazine (0.25-3 mg/kg) and detomidine (25 and 50 micrograms/kg) significantly increased the 2 and 24 h food intake from control values. Treatment of rats with the alpha 2-adrenoceptor antagonist yohimbine (1 mg/kg, i.p.) 15 min before xylazine (0.5 mg/kg, i.p.) or detomidine (50 micrograms/kg, i.p.) significantly inhibited the increase in food intake. Yohimbine treatments alone at 0.5, 1 and 2 mg/kg, i.p. did not significantly change the 2 and 24 h food intake from control values. The results suggest that the alpha 2-agonists xylazine and detomidine enhance food intake in rats.