Reliability, validity, and responsiveness of the Arabic version of HIT-6 questionnaire in patients with migraine indicated for preventive therapy: A multi-center study.

BACKGROUND: The Headache Impact Test (HIT-6) is an important patient-reported outcome measure (PROM) in migraine prevention trials. OBJECTIVES: This study aimed to (i) assess the reliability and validity of the Arabic version of HIT-6 in Arabic-speaking patients experiencing migraine, and (ii) evaluate the responsiveness of HIT-6 following migraine preventive therapy. METHODS: In this prospective study, patients with migraine (n = 145) were requested to fill out a headache diary, the Arabic version of HIT-6, and Migraine Disability Assessment Scale (MIDAS) at two time points (baseline and 3 months after initiation of prophylactic treatment). Some respondents (n = 73) were requested to fill out HIT-6 again 1 week from the baseline for test-retest reliability. The intensity of migraine headache attacks was evaluated using the Visual Analogue Scale (VAS). An anchor-based method was used to establish the minimal important change (MIC) value and responsiveness of HIT-6. RESULTS: The total scores of HIT-6 were significantly correlated to a fair degree with MIDAS (r = 0.41), as well as VAS (r = 0.53), and monthly migraine days (r = 0.38) at the baseline while at the follow-up (after 3 months), the correlations were of moderate degree with MIDAS scores (r = 0.62) and monthly migraine days (r = 0.60; convergent validity). Reliability estimates of the Arabic HIT-6 were excellent (Cronbach's α = 0.91 at baseline and 0.89 at follow-up). The average measure interclass correlation coefficient (ICC) value for the test-retest reliability was 0.96 (95% confidence interval = 0.94-0.98, p < 0.001). The HIT-6 total score is sensitive to change, being significantly reduced after prophylactic treatment compared to before (effect size = 1.5, standardized response mean = 1.3). A reduction from baseline of 4.5 on HIT-6 showed the highest responsiveness to predict improvement with an area under the curve equal to 0.66, sensitivity of 80%, specificity of 45%, and significance at 0.021. Changes in the HIT-6 total score were positively correlated with changes in monthly migraine days (r = 0.40) and VAS scores (r = 0.69) but not with changes in the score of MIDAS (r = 0.07). CONCLUSION: The Arabic version of HIT-6 is valid, reliable, and sensitive to detect clinical changes following migraine prophylactic treatment with a MIC of 4.5 points.

Quality, Reliability, and Readability of Online Information on Idiopathic Intracranial Hypertension.

BACKGROUND: To evaluate the quality & reliability, technical quality, and readability of patient-targeted online information on idiopathic intracranial hypertension. METHODS: In this cross-sectional study, we searched Google and Bing search engines for the terms "idiopathic intracranial hypertension" and "pseudotumor cerebri." We evaluated the first 50 search outcomes for each search term. Peer-reviewed articles, targeted advertisements, book chapters, videos, personal blogs, websites intended for healthcare professionals, and non-English websites were excluded. Websites were classified as institutional or private. Two independent reviewers assessed each website for 1) quality and reliability using DISCERN, Health on the Net Code of Conduct (HONcode), and JAMA criteria and 2) technical quality based on 11 criteria. Readability was evaluated using 6 measures (Flesch-Kincaid Reading Ease score and grade level, Gunning Fog, Simple Measure of Gobbledygook (Smog) index, Coleman-Liau index, and automated readability index). RESULTS: Sixty-three websites (37 institutional) were included. The mean scores for the DISCERN, HONcode, and JAMA criteria were 3.6 ± 1 (1-4.8; 1: worse, 5: best), 10.3 ± 2.8 (2-16; 0: worse, 16: best), and 2 ± 1.3 (0-4; 0: worse, 4: best), respectively. The mean technical quality score was 0.8 ± 0.1 (0.5-1). The mean Flesch-Kincaid grade level score was 8.9 ± 1.8 (3.3-13.3). For Flesch-Kincaid grade level, 47 (74.6%) websites scored a grade level of 10 or less. For Gunning Fog Score, 35 websites (55.6%) scored from 7.3 to 10.8. For the Smog Index, 46 (73%) websites scored 5.7-8. The mean Coleman Liau Index was 16 ± 2.1 (9.6-22.2). For the automated readability index, 30 (50.7%) websites scored less than the eighth grade. No statistically significant difference was present between institutional and private websites except for JAMA, which scored higher in private websites (2.4 vs 1.7, P = 0.03). CONCLUSIONS: Our findings suggest that online information on idiopathic intracranial hypertension/pseudotumor cerebri for patients generally demonstrates moderate to good quality and reliability. Although most websites maintain credible technical quality, the readability exceeds recommended levels for the average American reader. This may impede understanding, emphasizing the need for future improvements.

Clinical performance comparison between lithium disilicate and hybrid resin nano-ceramic CAD/CAM onlay restorations: a two-year randomized clinical split-mouth study.

A total of 20 lithium disilicate glass-ceramics (IPS e.max CAD, Ivoclar Vivadent) and 20 resin nano-ceramic (Voco Grandio Blocks) onlay restorations were performed in 20 patients using a split-mouth design to compare the two-year clinical performance of lithium disilicate and resin nano-ceramic onlay restorations. Both restorations were evaluated at baseline, one-year, and two-year clinical follow-ups based on the modified United States Public Health Service (USPHS) criteria. Chi-square and Fisher's exact tests showed no statistically significant difference between Voco Grandio and IPS e.max ceramic restorations for all evaluated parameters during the different follow-up periods (p > 0.05). Cochrane's and MC-Nemar's tests indicated statistically significant differences regarding color match within the Voco Grandio group. They also indicated statistically significant differences in marginal discoloration, marginal adaptation, surface texture, and postoperative hypersensitivity within both ceramic material groups (p < 0.05). Kaplan-Meier curve indicated that the survival rate of both ceramic materials was 90%. After two years of clinical service, IPS e.max CAD and Voco Grandio onlay restorations exhibited similar clinical performance.

Validity and reliability of Arabic version of pediatric migraine disability assessment scale (Child Self-Report versus Parent Proxy-Report): a multi-center study.

BACKGROUND: Pediatric Migraine Disability Assessment (PedMIDAS) is one of the most frequently used questionnaires to assess disability from migraine in pediatric patients. This work aimed to evaluate the validity and test-retest reliability of the Arabic version of the child self-report versus the parent proxy report PedMIDAS. We also aimed to test the agreement between children's and parents' reports of the scale. METHODS: PedMIDAS was subjected to translation and back-translation, then applied to 112 pediatric patients fulfilling the migraine diagnostic criteria. This cross-sectional study was conducted on two visits, one week apart. At visit 1, the following data were obtained from the included pediatric patients: disease duration, migraine type, current treatment regimen, monthly migraine days (MMD) during the last month preceding the enrollment, and migraine intensity using the visual analogue scale. Then, each child and his parent were independently asked to fill out PedMIDAS and Child Self-Report of the Pediatric Quality of Life Inventory™ 4.0 (PedsQL™) to test the convergent validity of PedMIDAS. At visit 2, each child was requested to complete PedMIDAS again, and so was the parent to evaluate test-retest reliability. RESULTS: Cronbach's alpha was estimated to be 0.94 for each instrument. For the child-self report PedMIDAS, the average measure intraclass correlation coefficient (ICC) value was 0.992 (95%CI = 0.989-0.995), while it was estimated to be 0.990 for the parent-proxy report with 95%CI = 0.985-0.993, indicating excellent test-retest reliability for both instruments. The child-self report and the parent-proxy report PedMIDAS scores were significantly correlated with MMD, VAS, and all domains of the corresponding PedsQL, supporting convergent validity for both instruments. Agreement between parent and child on disability grading categories of PedMIDAS was substantial (κ = 0.644). CONCLUSION: The Arabic version of PedMIDAS was a valid and reliable instrument to assess disability from migraine in Arabic-speaking pediatric patients with migraine. Parent reports can be valuable as a complement to child reports for a comprehensive assessment of migraine.

The characteristics of white dot syndromes following COVID-19 Vaccines: a systematic review.

PURPOSE: To review all studies reporting the onset of white dot syndromes following COVID-19 vaccines. METHODS: Our protocol was registered prospectively on PROSPERO [registration number: CRD42023426012]. We searched five different databases including PubMed, Scopus, Web of Science, Google Scholar, and Science Direct up to May 2023. All the studies that reported the occurrence of white dot syndrome following COVID-19 vaccines were included. All statistical tests were conducted with a 95% confidence interval and a 5% error margin. A p value of less than 0.05 was considered statistically significant. The methodological quality of included studies was performed using the IHE Quality Appraisal Checklist for Case Series studies and JBI Critical Appraisal Checklist for Case Reports. RESULTS: Fifty studies involving seventy-one subjects were included. Multiple evanescent white dot syndrome (MEWDS) was the most common disease (n = 25, 35.2% %), followed by acute macular neuroretinopathy (AMN) (n = 22, 31.0%) and acute posterior multifocal placoid pigment epitheliopathy (APMPPE) (n = 4, 5.6%). They were mostly unilateral (n = 50, 70.4%). The presenting symptoms were blurred vision (n = 26, 36.6%), paracentral scotoma (n = 19, 26.8%), visual field disturbance, and photopsia (n = 7, 9.9%). The mean duration for follow-up was 10.15 ± 14.04 weeks. Nineteen subjects (29.69%) received steroids with improvement reported in 68.4%. Eleven subjects (17.19%) were managed by observation only with reported full recovery and improvement. CONCLUSION: White dot syndromes are very rare entities. Our findings highlight a possible association between COVID-19 vaccines and the occurrence of white dot syndromes. However, larger studies with good quality should be implemented to confirm these findings.

New Air-Jet Dry Powder Insufflator for High-Efficiency Aerosol Delivery to Rats.

Pulmonary deposition of lung-targeted therapeutic aerosols can achieve direct drug delivery to the site of action, thereby enhancing the efficacy and reducing systemic exposure. In this study, we investigated the in vitro and in vivo aerosol performance of the novel small animal air-jet dry powder insufflator (Rat AJ DPI) using spray-dried albuterol excipient-enhanced-growth (EEG) powder as a model formulation. The in vitro aerosolization performance of the optimized albuterol EEG powder was first assessed using the Rat AJ DPI. The performance of Rat AJ DPI to deliver albuterol EEG aerosol to rat lungs was then compared to that of the Penn-Century Insufflator. Albuterol EEG powders dispersed using the Rat AJ DPI demonstrated narrow unimodal aerosol size distribution profiles, which were independent of the loaded powder dose (1, 2, and 5 mg). In addition, the span value for Rat AJ DPI (5 mg powder mass) was 1.32, which was 4.2-fold lower than that for Penn-Century insufflator (5 mg powder mass). At a higher loaded mass of 5 mg, the Rat AJ DPI delivered significantly larger doses to rat lungs compared with the Penn-Century DPI. The Rat AJ DPI with hand actuation delivered approximately 85% of the total emitted dose (2 and 5 mg loadings), which was comparatively higher than that for Penn-Century DPI (approximately 75%). In addition, percentage deposition in each of the lung lobes for the Rat AJ DPI was observed to be independent of the administration dose (2 and 5 mg loadings) with coefficients of variation below 12%, except in the right middle lobe. Automatic actuation of a 5 mg powder mass using the Rat AJ DPI demonstrated a similar delivered dose compared to manual actuation of the same dose, with 82% of the total emitted dose reaching the lung lobes. High-efficiency delivery of the aerosol to the lobar lung region and low sensitivity of the interlobar delivery efficiency to the loaded dose highlight the suitability of the new air-jet DPI for administering therapeutic pharmaceutical aerosols to small test animals.

Near Elimination of In Vitro Predicted Extrathoracic Aerosol Deposition in Children Using a Spray-Dried Antibiotic Formulation and Pediatric Air-Jet DPI.

PURPOSE: This study evaluated the in vitro aerosol performance of a dry powder antibiotic product that combined a highly dispersible tobramycin powder with a previously optimized pediatric air-jet dry powder inhaler (DPI) across a subject age range of 2-10 years. METHODS: An excipient enhanced growth (EEG) formulation of the antibiotic tobramycin (Tobi) was prepared using a small particle spray drying technique that included mannitol as the hygroscopic excipient and trileucine as the dispersion enhancer. The Tobi-EEG formulation was aerosolized using a positive-pressure pediatric air-jet DPI that included a 3D rod array. Realistic in vitro experiments were conducted in representative airway models consistent with children in the age ranges of 2-3, 5-6 and 9-10 years using oral or nose-to-lung administration, non-humidified or humidified airway conditions, and constant or age-specific air volumes. RESULTS: Across all conditions tested, mouth-throat depositional loss was < 1% and nose-throat depositional loss was < 3% of loaded dose. Lung delivery efficiency was in the range of 77.3-85.1% of loaded dose with minor variations based on subject age (~ 8% absolute difference), oral or nasal administration (< 2%), and delivered air volume (< 2%). Humidified airway conditions had an insignificant impact on extrathoracic depositional loss and significantly increased aerosol size at the exit of a representative lung chamber. CONCLUSIONS: In conclusion, the inhaled antibiotic product nearly eliminated extrathoracic depositional loss, demonstrated high efficiency nose-to-lung antibiotic aerosol delivery in pediatric airway models for the first time, and provided ~ 80% lung delivery efficiency with little variability across subject age and administered air volume.

Helicobacter pylori infection in migraine headache: a true association or an innocent bystander?

Much concern was directed towards the relationship between migraine and Helicobacter pylori (H. pylori) infection. Some researchers reported a strong association. Meanwhile, others have indicated totally negative results. The aim of this work was to clarify the association between migraine headaches and both H. pylori infection and Gastrointestinal (GIT) symptoms and to study their impact on the frequency and severity of migraine headache attacks.This is a case control study conducted on 77 migraine patients and 77 healthy controls. History was taken from the included patients regarding the frequency of migraine headache attacks/month and GIT symptoms including dyspepsia, flatulence, weight loss, and epigastric pain. Migraine Disability Assessment Test (MIDAS) and Visual Analogue Scale (VAS) were used for assessment of migraine severity. Helicobacter pylori was detected in the stool of the included patients and controls.There was a significantly higher prevalence of infection with H. pylori in migraine patients [77.9% (n = 60)] than control group [50.6% (n = 39)] (P-value˂ 0.001, Odds ratio= 3.439, 95% CI =1.708 - 6.923). The prevalence of dyspepsia, flatulence, and epigastric pain. was significantly higher in migraine patients in comparison to control group (P-value= 0.003, 0.017, 0.006 respectively). There was no effect of infection with H. pylori or presence of GIT symptoms on frequency of migraine attacks, MIDAS or VAS scores.GIT symptoms and H. pylori infection are more prevalent in patients with migraine compared to controls, however, they might not have an impact on the frequency or severity of migraine headache attacks.

Computational Fluid Dynamics (CFD) Guided Spray Drying Recommendations for Improved Aerosol Performance of a Small-Particle Antibiotic Formulation.

PURPOSE: The objective of this study was to implement computational fluid dynamics (CFD) simulations and aerosol characterization experiments to determine best-case spray drying conditions of a tobramycin excipient enhanced growth (Tobi-EEG) formulation for use in a pediatric air-jet dry powder inhaler (DPI). METHODS: An iterative approach was implemented in which sets of spray drying conditions were explored using CFD simulations followed by lead candidate selection, powder production and in vitro aerosol testing. CFD simulations of a small-particle spray dryer were performed to capture droplet drying parameters and surface-averaged temperature and relative humidity (RH) conditions in the powder collection region. In vitro aerosol testing was performed for the selected powders using the pediatric air-jet DPI, cascade impaction, and aerosol transport through a pediatric mouth-throat (MT) model to a tracheal filter. RESULTS: Based on comparisons of CFD simulations and in vitro powder performance, recommended drying conditions for small-particle powders with electrostatic collection include: (i) reducing the CFD-predicted drying parameters of κavg and κmax to values below 3 µm2/ms and 114 µm2/ms, respectively; (ii) maintaining the Collector Surface RH within an elevated range, which for the Tobi-EEG formulation with l-leucine was 20-30 %RH; and (iii) ensuring that particles reaching the collector were fully dried, based on a mass fraction of solute CFD parameter. CONCLUSIONS: Based on the newly recommended spray dryer conditions for small particle aerosols, delivery performance of the lead Tobi-EEG formulation was improved resulting in >60% of the DPI loaded dose passing through the pediatric MT model.

MicroRNA-22 Level in Patients with Multiple Sclerosis and Its Relationship with Vitamin D and Vitamin D Receptor Levels.

INTRODUCTION: Multiple sclerosis (MS) is known to be a multifactorial disorder. Numerous observational studies have suggested the implication of multiple genetic and environmental factors in the pathogenesis of MS. The aim of this work was to evaluate expression of the microRNA-22 (miRNA-22) level, in relation to vitamin D (VD) and VD receptor (VDR) levels in patients with MS during remission state. METHODS: This case-control study was conducted in 50 patients with clinically definite MS and 50 age- and sex-matched healthy controls. miRNA-22 expression was assessed in both MS patients and controls using quantitative RT-PCR. The serum level of VD and VDR was assessed in both MS patients and controls using ELISA techniques. RESULTS: The miRNA-22 level was significantly downregulated in MS patients in comparison to controls (p value <0.001). MS patients had also significantly lower VD and VDR levels in comparison to controls (p value <0.001 and <0.001, respectively). Patients with secondary progressive MS (SPMS) have a significantly higher miRNA-22 level than patients with relapsing remitting MS (RRMS) (p value = 0.042). There was a statistically significant positive correlation between the miRNA-22 level and EDSS (p value = 0.033). There was also a statistically significant positive correlation between the miRNA-22 level and VDR level (p value = 0.002). CONCLUSION: The miRNA-22 level was significantly downregulated in MS patients, but it had a positive correlation with disability status. Patients with SPMS have a significantly higher miRNA-22 level than patients with RRMS. VD and VDR levels were significantly lower in MS patients than controls. The miRNA-22 level was positively correlated with the VDR level.

Diagnostic accuracy of cardiac computed tomographic angiography and transesophageal echocardiography in evaluation of patients with prosthetic paravalvular leakage.

PURPOSE: Computed Tomography (CT) scan has been well addressed to provide diagnostic information for patients with prosthetic heart valve (PHV) dysfunction. However, its role in the assessment of patients with prosthetic paravalvular leakage (PVL) has not been studied thoroughly. So, this study was conducted to assess the feasibility, reproducibility, and accuracy of CT for diagnosis of prosthetic PVL using surgical findings as the reference standard. MATERIALS AND METHODS: This was a prospective cohort study that was conducted on 26 consecutive patients with suspected prosthetic PVL who underwent both transesophageal echocardiography (TEE) and 64-slice ECG-gated CT. The gold standard was the intraoperative findings. Surgery was performed on 26 patients. RESULTS: There was an excellent degree of agreement between CT and intraoperative findings for diagnosis, localization of prosthetic PVL. The perimeter of prosthetic PVL measured by CT was strongly correlated with echocardiographic severity of PVL by TEE (Spearman's Correlation Coefficient, r = .83, p = .0014). CONCLUSION: This study demonstrates that cardiac CT showed comparable diagnostic accuracy to TEE and intraoperative findings for the detection, localization, and assessment of severity of prosthetic PVL. Moreover, CT was shown to be useful in detection of other findings related to prosthetic cardiac valves.

Carnosic Acid Encapsulated in Albumin Nanoparticles Induces Apoptosis in Breast and Colorectal Cancer Cells.

Carnosic acid (CA) is a natural phenolic compound with several biomedical actions. This work was performed to study the use of CA-loaded polymeric nanoparticles to improve the antitumor activity of breast cancer cells (MCF-7) and colon cancer cells (Caco-2). CA was encapsulated in bovine serum albumin (BSA), chitosan (CH), and cellulose (CL) nanoparticles. The CA-loaded BSA nanoparticles (CA-BSA-NPs) revealed the most promising formula as it showed good loading capacity and the best release rate profile as the drug reached 80% after 10 h. The physicochemical characterization of the CA-BSA-NPs and empty carrier (BSA-NPs) was performed by the particle size distribution analysis, transmission electron microscopy (TEM), and zeta potential. The antitumor activity of the CA-BSA-NPs was evaluated by measuring cell viability, apoptosis rate, and gene expression of GCLC, COX-2, and BCL-2 in MCF-7 and Caco-2. The cytotoxicity assay (MTT) showed elevated antitumor activity of CA-BSA-NPs against MCF-7 and Caco-2 compared to free CA and BSA-NPs. Moreover, apoptosis test data showed an arrest of the Caco-2 cells at G2/M (10.84%) and the MCF-7 cells at G2/M (4.73%) in the CA-BSA-NPs treatment. RT-PCR-based gene expression analysis showed an upregulation of the GCLC gene and downregulation of the BCL-2 and COX-2 genes in cells treated with CA-BSA-NPs compared to untreated cells. In conclusion, CA-BSA-NPs has been introduced as a promising formula for treating breast and colorectal cancer.

The aquaporin4-IgG status and how it affects the clinical features and treatment response in NMOSD patients in Egypt.

BACKGROUND: In Egypt, the characterization of Neuromyelitis Optica Spectrum Disorder (NMOSD) is lacking. OBJECTIVES: To determine the demographics, clinical features, aquaporin4 antibodies (AQP4-IgG) status, and neuroimaging of Egyptian NMOSD patients. METHODS: Retrospective analysis of 70 NMOSD patients' records from the MS clinic, Kasr Alainy hospital, between January 2013 and June 2018. RESULTS: Patients' mean age was 34.9 ± 9.2 years, and the mean at disease onset was 28.9 ± 10.5 years. Fifty-nine patients had an initial monosymptomatic presentation. AQP4-IgG was measured using either enzyme-linked immunosorbent assay (ELISA) (22 patients) or cell-based assay (CBA) (34 patients). Six and 29 patients had positive results, respectively (p < 0.001). 84% had typical NMOSD brain lesions. Longitudinally extensive myelitis was detected in 49 patients, and 9 had either short segments or normal cords. Treatment failure was higher in seropositive patients. Rituximab significantly reduced the annualized relapse rate (ARR) compared to Azathioprine with a percentage reduction of (76.47 ± 13.28) and (10.21 ± 96.07), respectively (p = 0.04). Age at disease onset was the only independent predictor for disability (p < 0.01). CONCLUSION: Treatment failure was higher in seropositive patients. However, there was no difference in clinical or radiological parameters between seropositive and seronegative patients. Patients, who are polysymptomatic or with older age of onset, are predicted to have higher future disability regardless of the AQP4-IgG status.

Changes in migraine characteristics over 30 days of Ramadan fasting: A prospective study.

OBJECTIVE: To study Ramadan's effect on migraine from the start to the end of the month and the tolerability of patients with migraine to fasting. BACKGROUND: Fasting is a well-known trigger for migraine. Whether this effect on migraine is the same throughout the whole month, or whether it varies from the first to the last days of the month, has not been studied yet. METHODS: A prospective cohort observational study was carried out on persons with migraine who fasted from 24 April to 23 May during Ramadan 2020. Each patient was asked to fill out their headache diary starting from Shaaban (the month before Ramadan) to the end of Ramadan. The Ramadan diary was divided by 10 days each, by which the patient was asked to accurately describe their migraine attacks in terms of frequency, duration, and intensity by using the Visual Analog Scale. Migraine attacks during the first day of fasting were assessed separately. RESULTS: A total of 292 known persons with migraine from Egypt completed the study. Their median age was 33 years; 72/292 (24.7%) were male, and 220/292 (75.3%) were female. About 126/236 (53.4%) of the patients had migraine attacks on Ramadan's first day, most of them during fasting. The frequency of migraine attacks was significantly increased in Ramadan (median 4, interquartile range [IQR] 2-7) compared with Shaaban (median 3, IQR 1-6), p = 0.009. The number of attacks was significantly reduced in both the second (median 1, IQR 0-2.25) and the third 10 days of Ramadan (median 1, IQR 1-3) compared with the first 10 days (median 3, IQR 1-5) (p < 0.001 for each). CONCLUSION: Ramadan's potential exacerbating effect on the frequency of migraine attacks should be discussed with patients with migraine. This effect appears to be limited to the first 10 days of Ramadan and then subsides with successive days of fasting.

Impact of Ramadan fasting on disease activity in patients with multiple sclerosis: a multicenter study.

BACKGROUND: The safety of Ramadan fasting for Muslim patients suffering from multiple sclerosis (MS) is still a matter of debate. This work aimed to study the clinical course of MS during Ramadan fasting and to clarify the predictors of relapses and symptoms exacerbation. METHODS: This retrospective study included 153 Muslim patients with MS. Data related to the disease course before Ramadan were obtained from patients' files, whereas data related to the disease activity during Ramadan, were collected from patients over the two months following Ramadan. RESULTS: Patients with MS who experienced relapses, exacerbation of symptoms and development of new symptoms during Ramadan had a statistically significant longer disease duration compared to those who did not experience (P < 0.001, <0.001, 0.01 respectively). Also, patients who experienced relapses, exacerbation of symptoms and development of new symptoms during Ramadan had a statistically significant higher expanded disability status scale (EDSS) compared to those who did not experience (P <0.001, <0.001,0.01, respectively). The occurrence of relapses, exacerbation of symptoms and development of new symptoms during Ramadan, were significantly higher in patients who experienced relapses in the preceding year compared to those who did not (P= 0.002, 0.002, 0.01, respectively). Binary logistic regression revealed that each score elevation of EDSS increased the odds of relapse during Ramadan by 1.02 (P-value = 0.04). Also, each month's increase in disease duration increased the odds of relapse during Ramadan by 1.87 (P-value = 0.046). CONCLUSION: High EDSS and long disease duration are independent predictors of relapse during Ramadan.

High-Efficiency Dry Powder Aerosol Delivery to Children: Review and Application of New Technologies.

While dry powder aerosol formulations offer a number of advantages, their use in children is often limited due to poor lung delivery efficiency and difficulties with consistent dry powder inhaler (DPI) usage. Both of these challenges can be attributed to the typical use of adult devices in pediatric subjects and a lack of pediatric-specific DPI development. In contrast, a number of technologies have recently been developed or progressed that can substantially improve the efficiency and reproducibility of DPI use in children including: (i) nose-to-lung administration with small particles, (ii) active positive-pressure devices, (iii) structures to reduce turbulence and jet momentum, and (iv) highly dispersible excipient enhanced growth particle formulations. In this study, these technologies and their recent development are first reviewed in depth. A case study is then considered in which these technologies are simultaneously applied in order to enable the nose-to-lung administration of dry powder aerosol to children with cystic fibrosis (CF). Using a combination of computational fluid dynamics (CFD) analysis and realistic in vitro experiments, device performance, aerosol size increases and lung delivery efficiency are considered for pediatric-CF subjects in the age ranges of 2-3, 5-6 and 9-10 years old. Results indicate that a new 3D rod array structure significantly improves performance of a nasal cannula reducing interface loss by a factor of 1.5-fold and produces a device emitted mass median aerodynamic diameter (MMAD) of 1.67 µm. For all ages considered, approximately 70% of the loaded dose reaches the lower lung beyond the lobar bronchi. Moreover, significant and rapid size increase of the aerosol is observed beyond the larynx and illustrates the potential for targeting lower airway deposition. In conclusion, concurrent CFD and realistic in vitro analysis indicates that a combination of multiple new technologies can be implemented to overcome obstacles that currently limit the use of DPIs in children as young as two years of age.

Muscle Co-Activation around the Knee during Different Walking Speeds in Healthy Females.

The purpose of this study was to examine the changes in co-activation around the knee joint during different walking speeds in healthy females using the co-activation index. Ten healthy females (age: 21.20 ± 7.21 years, height: 164.00 ± 4.00 cm, mass: 60.60 ± 4.99 kg) participated in this study and performed three walking speeds (slow, normal, and fast). A Qualisys 11-camera motion analysis system sampling at a frequency of 200 Hz was synchronized with a Trigno EMG Wireless system operating at a 2000 Hz sampling frequency. A significant decrease in the co-activation index of thigh muscles was observed between the slow and fast, and between the normal and fast, walking speeds during all walking phases. A non-significant difference was observed between the slow and normal walking speeds during most walking phases, except the second double support phase, during which the difference was significant. A negative relationship was found between walking speed and the co-activation index of thigh muscles in all speeds during walking phases: first double support (r = -0.3386, p < 0.001), single support (r = -0.2144, p < 0.01), second double support (r = -0.4949, p < 0.001), and Swing (r = -0.1639, p < 0.05). In conclusion, the results indicated high variability of thigh muscle co-activation in healthy females during the different walking speeds, and a decrease in the co-activation of the thigh muscles with the increase of speed.

Computational Fluid Dynamics (CFD) Simulations of Spray Drying: Linking Drying Parameters with Experimental Aerosolization Performance.

PURPOSE: The purpose of this study was to develop a new computational fluid dynamics (CFD)-based model of the complex transport and droplet drying kinetics within a laboratory-scale spray dryer, and relate CFD-predicted drying parameters to powder aerosolization metrics from a reference dry powder inhaler (DPI). METHODS: A CFD model of the Buchi Nano Spray Dryer B-90 was developed that captured spray dryer conditions from a previous experimental study producing excipient enhanced growth powders with L-leucine as a dispersion enhancer. The CFD model accounted for two-way heat and mass transfer coupling between the phases and turbulent flow created by acoustic streaming from the mesh nebulizer. CFD-based drying parameters were averaged across all droplets in each spray dryer case and included droplet time-averaged drying rate (κavg), maximum instantaneous drying rate (κmax) and precipitation window. RESULTS: CFD results highlighted a chaotic drying environment in which time-averaged droplet drying rates (κavg) for each spray dryer case had high variability with coefficients of variation in the range of 60-70%. Maximum instantaneous droplet drying rates (κmax) were discovered that were two orders of magnitude above time-averaged drying rates. Comparing CFD-predicted drying parameters with experimentally determined mass median aerodynamic diameters (MMAD) and emitted doses (ED) from a reference DPI produced strong linear correlations with coefficients of determination as high as R2 = 0.98. CONCLUSIONS: For the spray dryer system and conditions considered, reducing the CFD-predicted maximum drying rate experienced by droplets improved the aerosolization performance (both MMAD and ED) when the powders were aerosolized with a reference DPI.

Dry powder aerosol containing muco-inert particles for excipient enhanced growth pulmonary drug delivery.

Tenacious sputum poses a critical diffusion barrier for aerosol antibiotics used to treat cystic fibrosis (CF) lung infection. We conducted a proof-of-concept study using dense poly(ethylene glycol) coated polystyrene nanoparticles (PS-PEG NPs) as model muco-inert particles (MIPs) formulated as a powder using an excipient enhanced growth (EEG) strategy, aiming to minimize extrathoracic airway loss, maximize deposition in the airway and further overcome the sputum barrier in the CF lungs. The EEG aerosol formulation containing PS-PEG MIPs was prepared by spray drying and produced discrete spherical particles with geometric diameter of approximately 2 µm; and >80% of the powder dose was delivered from a new small-animal dry powder inhaler (DPI). The MIPs released from the EEG aerosol had human airway mucus and CF sputum diffusion properties comparable to the suspension formulation. These properties make this formulation a promising pulmonary drug delivery system for CF lung infections.

Predicting Wins, Losses and Attributes' Sensitivities in the Soccer World Cup 2018 Using Neural Network Analysis.

Predicting the results of soccer competitions and the contributions of match attributes, in particular, has gained popularity in recent years. Big data processing obtained from different sensors, cameras and analysis systems needs modern tools that can provide a deep understanding of the relationship between this huge amount of data produced by sensors and cameras, both linear and non-linear data. Using data mining tools does not appear sufficient to provide a deep understanding of the relationship between the match attributes and results and how to predict or optimize the results based upon performance variables. This study aimed to suggest a different approach to predict wins, losses and attributes' sensitivities which enables the prediction of match results based on the most sensitive attributes that affect it as a second step. A radial basis function neural network model has successfully weighted the effectiveness of all match attributes and classified the team results into the target groups as a win or loss. The neural network model's output demonstrated a correct percentage of win and loss of 83.3% and 72.7% respectively, with a low Root Mean Square training error of 2.9% and testing error of 0.37%. Out of 75 match attributes, 19 were identified as powerful predictors of success. The most powerful respectively were: the Total Team Medium Pass Attempted (MBA) 100%; the Distance Covered Team Average in zone 3 (15-20 km/h; Zone3_TA) 99%; the Team Average ball delivery into the attacking third of the field (TA_DAT) 80.9%; the Total Team Covered Distance without Ball Possession (Not in_Poss_TT) 76.8%; and the Average Distance Covered by Team (Game TA) 75.1%. Therefore, the novel radial based function neural network model can be employed by sports scientists to adapt training, tactics and opposition analysis to improve performance.