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OBJECTIVE: To investigate whether cutoff value of 5.6 mmol/l for impaired fasting glucose (IFG) improves the prediction of Type 2 diabetes mellitus (T2DM) in comparison to the 6.1 mmol/l value. RESEARCH DESIGN AND METHODS: A total of 5794 non-diabetic subjects aged 42+/-13 years were followed for 6.5 years. T2DM was defined based on the WHO 1999 criteria. Cox regression analysis was used to calculate the relative risk (RR) of developing T2DM. Model discrimination was assessed by calculating the area under the receiver operating characteristic curve (AUC). RESULTS: During the follow-up, there were 351 incident T2DM. The RR (95% CI) of the 6.1 and 5.6 mmol/l cutoffs were comparable in both univariate and multivariate analysis [9.6 (7.5-12.3) vs. 8.4 (6.4-10.0), respectively in univariate and 2.4 (1.8-3.2) vs. 3.3 (2.6-4.2), respectively in multivariate models]. Using the 5.6 mmol/l cutoff value in the multivariate model significantly improved its discrimination in comparison to the 6.1 mmol/l value [AUC (95% CI): 0.78 (0.74-0.83) vs. 0.74 (0.70-0.79), P<0.01]. Models with impaired glucose tolerance and fasting glucose had the highest AUC of 0.81(95% CI: 0.78-0.85). CONCLUSIONS: The 5.6 mmol/l cutoff value of IFG combined with other diabetes risk factors performs significantly better than the 6.1 mmol/l value for prediction of future T2DM. [ABSTRACT FROM AUTHOR]

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Abstract Background Diabetes is a strong risk factor for cardiovascular disease (CVD).The relative role of various lipid measures in determining CVD risk in diabetic patients is still a subject of debate. We aimed to compare performance of different lipid measures as predictors of CVD using discrimination and fitting characteristics in individuals with and without diabetes mellitus from a Middle East Caucasian population. Methods The study population consisted of 1021 diabetic (men = 413, women = 608) and 5310 non-diabetic (men = 2317, women = 2993) subjects, aged ≥ 30 years, free of CVD at baseline. The adjusted hazard ratios (HRs) for CVD were calculated for a 1 standard deviation (SD) change in total cholesterol (TC), log-transformed triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), non-HDL-C, TC/HDL-C and log-transformed TG/HDL-C using Cox proportional regression analysis. Incident CVD was ascertained over a median of 8.6 years of follow-up. Results A total of 189 (men = 91, women = 98) and 263(men = 169, women = 94) CVD events occurred, in diabetic and non-diabetic population, respectively. The risk factor adjusted HRs to predict CVD, except for HDL-C, TG and TG/HDL-C, were significant for all lipid measures in diabetic males and were 1.39, 1.45, 1.36 and 1.16 for TC, LDL-C, non- HDL-C and TC/HDL-C respectively. In diabetic women, using multivariate analysis, only TC/HDL-C had significant risk [adjusted HR1.31(1.10-1.57)].Among non-diabetic men, all lipid measures, except for TG, were independent predictors for CVD however; a 1 SD increase in HDL-C significantly decreased the risk of CVD [adjusted HR 0.83(0.70-0.97)].In non-diabetic women, TC, LDL-C, non-HDL-C and TG were independent predictors. There was no difference in the discriminatory power of different lipid measures to predict incident CVD in the risk factor adjusted models, in either sex of diabetic and non-diabetic population. Conclusion Our data according to important test performance characteristics provided evidence based support for WHO recommendation that along with other CVD risk factors serum TC vs. LDL-C, non-HDL-C and TC/HDL-C is a reasonable lipid measure to predict incident CVD among diabetic men. Importantly, HDL-C did not have a protective effect for incident CVD among diabetic population; given that the HDL-C had a protective effect only among non- diabetic men.

Abstract Background The Middle East is estimated to have the largest increase in prevalence of diabetes by 2030; yet there is lack of published data on the incidence of Type 2 diabetes in this region. This study aimed to estimate Type 2 diabetes incidence and its associated risk factors in an Iranian urban population. Methods Among 3307 non-diabetics ≥ 20 years (mean age 42 ± 13 years, 42% males), glucose tolerance test was performed at baseline in 1999–2001 and at two consecutive phases in 2001–2005 and 2005–2008. Diabetes and glucose tolerance status were defined according to the ADA 1997 criteria. Logistic regression was used to determine the independent variables associated with incident diabetes and their odds ratios (OR). Results After median follow-up of 6 years, 237 new cases of diabetes were ascertained corresponding to an age and sex standardized cumulative incidence of 6.4% (95%CI: 5.6–7.2) and incidence rate of 10.6 (9.2–12.1) per 1000 person years. Besides classical diabetes risk factors, female sex and low education level significantly increased risk of diabetes in age adjusted models. In full model, the independent predictors were age [OR, 95%CI: 1.2 (1.1–1.3)], family history of diabetes [1.8 (1.3–2.5)], body mass index ≥ 30 kg/m2 [2.3 (1.5–3.6)], abdominal obesity [1.9 (1.4–2.6)], high triglyceride [1.4 (1.1–1.9)], Isolated impaired fasting glucose (IFG) [7.4 (3.6–15.0)], Isolated impaired glucose tolerance (IGT) [5.9 (4.2–8.4)] and combined IFG and IGT [42.2 (23.8–74.9)]. Conclusion More than 1% of the Iranian urban population older than 20 years develops Type 2 diabetes each year. Combination of IFG and IGT was the strongest predictor of incident diabetes among the modifiable risk factors.

Abstract Background To investigate the association of Aspartate aminotransferase (AST), Alanin aminotranferase (ALT) and Gamma glutamyl transferase (GGT) with incident type 2 diabetes. Methods In a nested case-control study, AST, ALT, GGT as well as classic diabetes risk factors, insulin and C-reactive protein (CRP) were measured in 133 non-diabetic subjects at baseline of which 68 were cases and 65 were controls. Incident diabetes was defined by the WHO 1999 criteria. Conditional logistic regression was used to calculate the odds ratio (OR) of incident diabetes associated with different hepatic markers. We used factor analysis for clustering of classic diabetes risk factors. Results In Univariate analysis both ALT and GGT were associated with diabetes with ORs of 3.07(1.21–7.79) and 2.91(1.29–6.53) respectively. After adjustment for CRP and insulin, ALT and GGT were still predictive of incident diabetes. When the model was further adjusted for anthropometric, blood pressure and metabolic factors, only ALT was independently associated with diabetes [OR = 3.18 (1.02–9.86)]. No difference was found between the area under the receiver operating characteristic curves of the models with and without ALT (0.820 and 0.802 respectively, P = 0.4) Conclusion ALT is associated with incident type 2 diabetes independent of classic risk factors. However, its addition to the classic risk factors does not improve the prediction of diabetes.

Abstract Background To estimate the prevalence of diagnosed and undiagnosed diabetes mellitus, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and combined IFG/IGT in a large urban Iranian population aged ≥ 20 years. Methods The study population included 9,489 participants of the Tehran Lipid and Glucose Study with full relevant clinical data. Age-standardized prevalence of diabetes and glucose intolerance categories were reported according to the 2003 American Diabetes Association definitions. Age-adjusted logistic regression models were used to estimate the numbers needed to screen (NNTS) to find one person with undiagnosed diabetes. Results The prevalence of diagnosed and undiagnosed diabetes, isolated IFG, isolated IGT, and combined IFG/IGT were 8.1%, 5.1%, 8.7%, 5.4% and 4.0% in men and 10%, 4.7%, 6.3%, 7.6%, and 4.5% in women respectively. Participants with undiagnosed diabetes had higher age, body mass index (BMI), waist circumference, systolic and diastolic blood pressures, triglycerides (all p values 2), abdominal obesity, hypertriglyceridemia, hypertension and low HDL-cholesterol levels. Among men, a combination of increased BMI, hypertension, and family history of diabetes led to a NNTS of 1.6 (95% CI: 1.57–1.71) and among women a combination of family history of diabetes and abdominal obesity, yielded a NNTS of 2.2 (95% CI: 2.1–2.4). Conclusion In conclusion, about one third of Tehranian adults had disturbed glucose tolerance or diabetes. One- third of total cases with diabetes were undiagnosed. Screening individuals with BMI ≥ 25 kg/m2 (men), hypertension (men), abdominal obesity (women) and family history of diabetes may be more efficient.

Objective: Refugees are highly vulnerable to mental health disorders and head injuries. The primary aim of this study is to examine the impact of posttraumatic stress disorder (PTSD) and head injury on reactive and appetitive aggression in adult Syrian refugees in Lebanon., Method: A cross-sectional study was conducted targeting adult Arab United Nations High Commissioner for Refugees-registered Syrian refugees residing in Beirut and southern regions of Lebanon. Eligible refugees completed a battery of questionnaires including the PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders, fifth edition, the Trauma Events and Head Injury sections of the Harvard Trauma Questionnaire, the Buss-Perry Aggression Questionnaire, and the Appetitive Aggression Scale., Results: A total of 191 Syrian refugees participated in the study: 62.83% were females, and the mean age was 31.01 years ( SD = 10.98). The severity of PTSD (adjusted B = 0.18, 95% CI [0.05, 0.31], p = .006), having experienced at least one head injury trauma event (adjusted B = 10.20, 95% CI [1.61, 18.79], p = .020), and the severity of somatic symptoms (adjusted B = 0.71, 95% CI [0.23, 1.20], p = .004) were significant risk factors of reactive aggression. As for appetitive aggression, males (females adjusted OR [a OR ] = 0.06, 95% CI [0.02, 0.18], p < .001), younger individuals (a OR = 0.95, 95% CI [0.91, 0.99], p = .024), and higher severity of somatic symptoms (a OR = 1.20, 95% CI [1.09, 1.32], p < .001) were significant risk factors., Conclusions: PTSD and head injury are independent risk factors for reactive aggression but not appetitive aggression in Syrian refugees in Lebanon, while the severity of somatic symptoms is an independent risk factor for both reactive and appetitive aggression. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

Purpose: To cross-culturally adapt and validate the Radboud Dysarthria Assessment (RDA) and the speech component of the Radboud Oral Motor inventory for Parkinson's disease (ROMP-speech) into the Arabic language among Lebanese subjects with dysarthria., Materials and Methods: This study included 50 participants with dysarthria. The Arabic versions of the RDA (A-RDA) and the ROMP-speech (A-ROMP-speech) were administered in addition to the Arabic Speech Intelligibility test, the Lebanese Voice Handicap Index-10 (VHI-10lb) and semantic verbal fluency tasks. The maximum performance tasks were analyzed using the Praat software. The A-RDA qualitative recording form and the A-ROMP-speech were assessed for construct validity and internal consistency. The convergent validity of the maximum performance tasks, the severity scale, and the A-ROMP-speech were evaluated., Results: Exploratory factor analysis of the qualitative recording form extracted 3 factors explaining 82.973% of the total variance, and it demonstrated high internal consistency (α = 0.912). The maximum performance tasks of the RDA correlated significantly with the corresponding Praat scores. The severity scale and the A-ROMP-speech correlated fairly to strongly with the Arabic Speech Intelligibility test (r s =-0.695 and -0.736, p  < 0.001) and the VHI-10lb ( r  = 0.539 and 0.640, p  < 0.001)., Conclusion: The A-RDA and the A-ROMP-speech are valid and reliable dysarthria tools among Lebanese subjects.

Background and Objective: This study aims to assess the effect of swim exercise along with consumption of bindii hydroalcoholic extract on memory and the oxidative stress markers in old male rats., Materials and Methods: This study was conducted on 32 old (400-500 g) and eight young male Wistar rats. The groups included young, old, old bindii (200 mg/kg), old exercise, and old bindii exercise (concurrent swimming training). All interventions were performed within 14 days. The animals' spatial memory was evaluated by the Y maze, radial maze, and shuttle box, Oxidative stress factors were also measured., Results: Compared to the old control group, the bindii extract along with swimming exercise significantly increased the periodic behavior percentage in the Y maze and the delay time in entry into the dark chamber in the shuttle box but no significant difference was seen in the reference memory error in the radial maze. Also, a significant increase in the amount of catalase (CAT) and antioxidant capacity (TAC) and a significant decrease in the amount of malondialdehyde (MDA) were observed in all treatment groups., Conclusion: These results show that exercise, along with the bindii extract consumption, can improve spatial and avoidance memory in old rats probably through the reduction of oxidative stress effects.

Cannabis is one of the most commonly utilized recreational drugs. However, increasing evidence from the literature suggests harmful implications on cognition. Thus, the main aim of the current review is to summarize literature findings pertaining to the impact of cannabis on neurocognitive skills, focusing on the imaging biomarkers provided by MRI. Two reviewers navigated the literature independently using four main search engines including PubMed and Cochrane. Articles were first evaluated through their title and abstract, followed by full-text assessment. Study characteristics and findings were extracted, and the studies' quality was appraised. 47 articles were included. The majority of the studies were of a case-control design (66%), and the most studied neurocognitive skill was memory (40.4%). With task-based fMRI being the most commonly utilized MRI technique, findings have shown significantly varying decreased and increased neuronal activity within brain regions associated with the cognitive tasks performed. Results suggest that cannabis users are significantly suffering from cognitive deficits. The major significance of this review is attributed to highlighting the role of MRI. Future research needs to delve more into validating the negative effects of cannabis, to enable stakeholders to take action to limit cannabis usage, to foster public health and wellbeing.

Objective: In this study, we aimed to explore the prevalence and determinants of common mental health disorders (CMHDs, posttraumatic stress disorder [PTSD], depression, and anxiety) in Syrian refugees in Lebanon. Specifically, we examined how the associations between cultural adversities (discrimination, unemployment, and separation from family) and CMHDs are modified by levels of religiosity and sex., Method: Between March and June 2017, a cross-sectional study was conducted targeting adult Arab Syrian refugees residing in Beirut and Southern Lebanon. Eligibility criteria comprised being a United Nations High Commissioner for Refugees-registered Syrian refugee residing in Lebanon, 18 years and older, and having no history of mental disorder or physical disability. A total of 191 refugees agreed to participate and complete a battery of six questionnaires. Exposures were measured using a sociodemographic questionnaire, the Postmigration Living Difficulties Checklist, the Harvard Trauma Questionnaire, and the Belief into Action Scale, while outcomes were measured using the Posttraumatic Stress Disorder Checklist for DSM-5 and the Depression and Anxiety Scale-21 Items., Results: Half (50.3%) of our sample had high PTSD risk, 73.8% had high depression risk, and 73.8% had high anxiety risk. Stratified analysis revealed religiosity and sex to be effect modifiers of the associations between cultural adversities and CMHDs. Specifically, cultural adversities were only significantly associated with CMHDs in the low religiosity stratum and males. Only unemployment was a significant risk factor for PTSD in both males ( OR = 4.53, 95% CI [1.44, 14.27]) and females ( OR = 2.77, 95% CI [1.14, 6.74])., Conclusions: Religiosity and sex are effect modifiers of the associations between cultural adversities and CMHDs. Religious and spiritual interventions in mental health care should be adopted in refugee settings. Moreover, there is an urgent need for capacity-building initiatives addressing social determinants of mental health among Syrian refugees in Lebanon. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Ever since the discovery of the brain's orexin/hypocretin system, most research was directed toward unveiling its contribution to the normal functioning of individuals. The investigation of reward-seeking behaviors then gained a lot of attention once the distribution of orexinergic neurons was revealed. Here, we discuss findings on the involvement of orexins in social interaction, a natural reward type. While some studies have succeeded in defining the relationship between orexin and social interaction, the controversy regarding its nature (direct or inverse relation) raises questions about what aspects have been overlooked until now. Upon examining the literature, we identified a research gap concerning conditions influencing the impact of orexins on social behavior expression. In this review, we introduce a number of factors (e.g., stress, orexin's source) that must be considered while studying the role of orexins in social interaction. Furthermore, we refer to published research to investigate the stage at which orexins affect social interaction and we highlight the nucleus accumbens (NAc) shell's role in social interaction and other rewarding behaviors. Finally, the underlying orexin molecular pathway influencing social motivation in particular illnesses is proposed. We conclude that orexin's impact on social interaction is multifactorial and depends on specific conditions available at a time.

Noscapine, a phthalide isoquinoline alkaloid isolated from the opium poppy, alongside cotarnine, a tetrahydroisoquinoline (THIQ) scaffold produced by the oxidative degradation of noscapine, has exhibited antitumor activities against several types of cancer. Although derivatization with amino acids is regarded as a promising strategy to improve chemotherapeutics' anticancer properties, amino acid conjugates of noscapine and cotarnine have been the least investigated. In the present study, 20 amino acid conjugated derivatives of noscapine and cotarnine at the 6-position were synthesized and evaluated for anticancer activity in both in vitro and in vivo conditions. Analysis of the antiproliferative activity against 4T1 mammary carcinoma tumor cells showed that compounds 6h (noscapine-phenylalanine), 6i (noscapine-tryptophan), and 10i (cotarnine-tryptophan) with IC 50 values of 11.2, 16.3, and 54.5 μM, respectively, were found to be far more potent than noscapine (IC 50 = 215.5 μM) and cotarnine (IC 50 = 575.3 μM) and were consequently opted for further characterization. Annexin V and propidium iodide staining followed by flow cytometry demonstrated improved apoptotic activity of compounds 6h , 6i , and 10i compared to those of noscapine and cotarnine. In a murine model of 4T1 mammary carcinoma, noscapine-tryptophan inhibited tumor growth more effectively than noscapine and the other amino acid conjugates without adverse effects. Moreover, molecular docking studies conducted on tubulin as the intracellular target of noscapine suggested a good correlation with experimental observations. Based on these results, noscapine-tryptophan could be a promising candidate for further preclinical investigations., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Background: Because of the association of lumbar lordosis with some clinical conditions such as low back pain, the chiropractic field has emphasized the significance of evaluating the lumbar lordotic status, by measuring Cobb's angle, regarded as the radiological gold standard, for the assessment of lumbar lordosis, on lateral radiographs. However, research has shown that this technique has some considerable drawbacks, mostly in terms of low accuracy and high variability between clinicians when compared with other radiological modalities. The main objective was to compare the diagnostic accuracy of newly established radiological measurements with one of Cobb's angle methods, for the characterization of lumbar lordosis status in a sample of Lebanese patients aged 15 and above., Material and Methods: This retrospective single-center study consisted of measuring Cobb's L1-S1 and Cobb's L1-L5 angles, along with the novel established measurements which are the derivative and the normalized surface area, on 134 lateral radiographs of the lumbar spine of Lebanese patients aged fifteen years old and above, gotten from the Radiology department at Zahra'a's Hospital in Beirut, performed by two observers using MATLAB. Inter-rater agreement was assessed by calculating the Intra-class correlation coefficients. Spearman correlation was analyzed between both Cobb's angle methods and with the derivative and normalized area respectively. 54 patients of the sample were diagnosed by two radiologists, according to their LL status. ROC curve analysis was performed to compare the diagnostic accuracy of the four techniques used. Data were analyzed with IBM SPSS Statistics 23.0 (NY, USA); P  < 0.05 was considered statistically significant., Results: According to the ROC curve analysis the new methods, which are the derivative and the normalized surface area, displayed lower diagnostic accuracy (AUC derivative  = 0.818 and 0.677, AUC surface area  = 0.796 and 0.828) than Cobb's L1-L5 (AUC L1-L5  = 0.924 and 0.929 values) and L1-S1 (AUC L1-S1  = 0.971 and 0.955) angles, in the characterization of hypo and hyperlordotic patients, respectively, in our Lebanese sample consisting of patients aged 15 and above, because of their lower area under the curve's values compared to the traditional Cobb's techniques. The Cobb's L1-S1 has shown to have the highest diagnostic accuracy among the four methods to characterize normal patients from hypo and hyperlordotic ones, by referring to its highest area under the curve's values. However, the sensitivity of Cobb's L1-L5 angle in characterizing hyperlordotic patients was similar to the one of the normalized surface area with a value of 100%.Conclusion: among the four modalities, the new methods didn't show a better diagnostic accuracy compared to the traditional modalities. Cobb's L1-S1 displayed the highest diagnostic accuracy despite its drawbacks. Further prospective studies are needed to validate the cut-offs obtained for Cobb's L1-S1 angle in our sample., 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., (© 2023 The Authors. Published by Elsevier Ltd.)

Why do some cultures invest more for the long term, whereas others emphasize living in the moment? We took advantage of a natural experiment in Iran to test the theory that long-term water scarcity is an important cause of differences in long-term orientation and indulgence. We found that Iranians in a water-scarce province reported more long-term orientation and less indulgence than did Iranians in a nearby water-rich province (Study 1, N = 331). In a field study, Iranians in the water-scarce province sent more résumés for a long-term job ad we posted, whereas Iranians in the water-rich province sent more résumés for a short-term, flexible job (Study 2, N = 182). College students in Iran primed to think about increasing water scarcity in the environment endorsed long-term orientation more and indulgence less (Study 3, N = 211). Across 82 countries, long-run water scarcity predicted long-term orientation (Study 4). In sum, cultures in water-scarce environments value thinking for the long term more and indulgence less.

Background/objective: Multiple Sclerosis is a common demyelinating disease of the central nervous system. Several studies suggested a link between vitamin D deficiency and multiple sclerosis disease activity, which can be evaluated by magnetic resonance imaging. Thereby, the main objective of the following scoping review is to summarize the magnetic resonance imaging findings assessing the probable effects of vitamin D on MS disease activity., Methodology: PRISMA checklist for systematic reviews and meta-analyses was employed to structure this review. Literature was searched for observational and clinical studies tackling the given matter using several search engines including PubMed, CORE, and Embase. Data was extracted in a systematic manner, and the articles meeting the inclusion criteria were quality-assessed by Jadad scale for randomized clinical trials (RCTs) and Newcastle-Ottawa scale for observational studies., Results: A total of 35 articles were included. Twenty-one (60%) studies noted a statistically significant association between vitamin D and Multiple Sclerosis MRI-detected disease activity. MRI-detected features involved lower contrast-enhancing T1 lesions, lower hyperintense T2 lesions, and a decrease in lesions volume. On the other hand, 40% (14 articles) of the articles did not detect any significant effect of vitamin D on Multiple Sclerosis disease activity. Due to the heterogeneity of the studies involved, meta-analysis was not employed in the given review., Discussion/conclusion: There was an abundance in the number of research studies investigating the relationship between vitamin D and Multiple Sclerosis while highlighting the significant role of MRI in assessing the activity of the disease. Numerous studies found that higher serum vitamin D levels are associated with decreased new active cortical and subcortical lesions and lower lesions volume. These findings highlight the importance of imaging modalities in the various aspects of neurological diseases and encourage further research to focus on the preventive effects of vitamin D on MS patients., (© 2023 The Authors.)

Aims: Traumatic brain injury (TBI) constitutes a serious public health concern. Although TBI targets the brain, it can exert several systemic effects which can worsen the complications observed in TBI subjects. Currently, there is no FDA-approved therapy available for its treatment. Thus, there has been an increasing need to understand other factors that could modulate TBI outcomes. Among the factors involved are diet and lifestyle. High-fat diets (HFD), rich in saturated fat, have been associated with adverse effects on brain health., Main Methods: To study this phenomenon, an experimental mouse model of open head injury, induced by the controlled cortical impact was used along with high-fat feeding to evaluate the impact of HFD on brain injury outcomes. Mice were fed HFD for a period of two months where several neurological, behavioral, and molecular outcomes were assessed to investigate the impact on chronic consequences of the injury 30 days post-TBI., Key Findings: Two months of HFD feeding, together with TBI, led to a notable metabolic, neurological, and behavioral impairment. HFD was associated with increased blood glucose and fat-to-lean ratio. Spatial learning and memory, as well as motor coordination, were all significantly impaired. Notably, HFD aggravated neuroinflammation, oxidative stress, and neurodegeneration. Also, cell proliferation post-TBI was repressed by HFD, which was accompanied by an increased lesion volume., Significance: Our research indicated that chronic HFD feeding can worsen functional outcomes, predispose to neurodegeneration, and decrease brain recovery post-TBI. This sheds light on the clinical impact of HFD on TBI pathophysiology and rehabilitation as well., Competing Interests: Declaration of competing interest The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Aggression towards nurses in the workplace arises from various reasons, reportedly increasing during the COVID-19 pandemic. Where aggression can be maintained by spiritual well-being, as it is said that spirituality is a coping skill and psychological well-being maintainer-but there is little known, especially during the pandemic. Thus, this study explored the effect of spirituality on aggression among the nurses working in the COVID-19 wards., Methods: This cross-sectional data from 200 nurses involved in the COVID-19 patient treatment were collected using a random sampling method from four hospitals in East Mazandaran province, Iran. Responses were collected based on socio-demographics, Buss-Perry Aggression Questionnaire, and Paloutzian & Ellison Spiritual Well-being Scale. T-test, ANOVA, Pearson correlation coefficient, and multiple linear regression were applied for data analysis., Results: The mean age of nurses was 31.49±6.88 (range: 21-48) years. Nurses working in the COVID-19 wards have a mean score of spiritual health of 67.21±12.84 (out of 120), whereas 51.77±10.96 (out of 116) was for aggression. The results showed a significant negative weak correlation between aggression and spiritual health (r = -.285, p<0.01). As per regression analysis, spiritual health [β = -.264], age [β = -.374], and working experience [β = 4.156] were the significant factors associated with aggression (p<0.05)., Conclusions: It is evident that nurses who consider spirituality in their life actions are in a state of reduced negative emotions, such as aggression. Thus, policymakers and managers of the healthcare settings are suggested to promote spirituality among the nurses through spiritual care education, providing the ground for promoting spirituality and a positive attitude towards it., Competing Interests: The authors of the research work do not have any conflict of interest., (Copyright: © 2022 Harati 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.)

Medulloblastoma is the most common malignant brain tumor of childhood accounting for about 60% of all pediatric embryonal tumors. Despite improvements in the overall survival rate, this tumor still lacks an efficient, reliable, and less toxic therapeutic approach. Characterization of the molecular mechanisms involved in medulloblastoma initiation and progression is a crucial step for the development of effective therapies. Signal transducer and activator of transcription 3 is a convergence point for several signaling cascades that are implicated in medulloblastoma tumorigenesis. Accumulated evidence has revealed the pivotal role of signal transducer and activator of transcription 3 in medulloblastoma pathogenesis such as proliferation, survival, angiogenesis, and immunosuppression as well as maintenance, drug resistance, and recurrence. In this review, we focus on the role of signal transducer and activator of transcription 3 in medulloblastoma tumorigenesis and discuss the recent advances of signal transducer and activator of transcription 3 inhibition as a promising developed strategy for medulloblastoma therapy., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Dysarthria is a common and persisting sequela to stroke. It can have a negative influence on psychological wellbeing, and quality of life. This systematic review aimed to describe and identify the neuroanatomical regions associated with non-progressive dysarthria following stroke., Methods: A systematic search of PubMed, Ovid Medline, CINAHL, Cochrane, Scopus, and ScienceDirect was conducted to identify all relevant articles published in peer-reviewed journals up to December 2021. Following data extraction, the National Institutes of Health (NIH) quality assessment tools were used to evaluate the methodological quality of the included studies., Results: Out of 2186 papers found in the literature related to dysarthria post-stroke, 24 met the inclusion criteria. Eligible articles assessed 1150 post-stroke subjects. Out of them, 420 subjects had dysarthria from isolated lesions. Regarding dysarthric subjects with ischemic strokes, 153 sustained supratentorial infarctions, while 267 had infratentorial infarctions. The majority had pontine infarctions (n = 142), followed by infarctions in the corona radiata (n = 104), and the cerebellum (n = 64)., Conclusion: This systematic review is the first step toward establishing a neuroanatomical model of dysarthria throughout the whole brain. Our findings have many implications for clinical practice and provide a framework for implementing guidelines for early detection and management of dysarthria post-stroke., (© 2022. The Author(s).)

The prevalence of obesity tripled worldwide between 1975 and 2016, and it is projected that half of the US population will be overweight by 2030. The obesity pandemic is attributed, in part, to the increasing consumption of the high-fat, high-carbohydrate Western diet, which predisposes to the development of the metabolic syndrome and correlates with decreased cognitive performance. In contrast, the high-fat, low-carbohydrate ketogenic diet has potential therapeutic roles and has been used to manage intractable seizures since the early 1920s. The brain accounts for 25% of total body glucose metabolism and, as a result, is especially susceptible to changes in the types of nutrients consumed. Here, we discuss the principles of brain metabolism with a focus on the distinct effects of the Western and ketogenic diets on the progression of neurological diseases such as epilepsy, Parkinson's disease, Alzheimer's disease, and traumatic brain injury, highlighting the need to further explore the potential therapeutic effects of the ketogenic diet and the importance of standardizing dietary formulations to assure the reproducibility of clinical trials., (© The Author(s) 2022. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To determine the clinical characteristics and outcomes of COVID-19 in a large cohort of new cancer patients referred to an oncology clinic in the north of Iran., Methods: During the 20-month COVID-19 pandemic, new cancer patients were followed-up. Demographic, pathologic, and clinical variables were collected for each patient. COVID-19 was confirmed based on a positive polymerase chain reaction test. Analyses were performed using the STATA version 14.0 at a significance level of 0.05., Results: In this study, 1294 new cancer patients were followed for 24 months (mean age: 58.7 years [range 10-95]). During the study period, COVID-19 was diagnosed in 9.4% of the patients with hospitalization rate of 3.4%, an ICU admission rate of 0.7%, and COVID-19 mortality rate of 4.9%. Hematological malignancies (OR U = 2.6, CI95% 1.28-5.34), receiving palliative treatments (OR A =3.03, CI95% 1.6-5.45) and receiving radiotherapy (OR A =2.07, 1.17-3.65) were the most common predictive factors of COVID infection in cancer patients. Also, the COVID mortality was higher in brain cancer patients ( p  = 0.07), metastatic disease ( p  = 0.01) and patients receiving palliative treatments ( p  = 0.02)., Conclusion: In patients suffering from cancer, COVID-19 infection can be predicted by cancer type, palliative care, and radiotherapy in cancer patients. Furthermore, brain cancers, metastasis, and palliative care were all associated with COVID-19-related mortality.

Background: Data on the efficacy and safety of COVID-19 vaccines in patients with malignancy are immature. In this paper, we assessed the literature involving the use of COVID-19 vaccines in cancer patients and reported the seroconversion rates as the main outcome and severity of COVID-19 infection and side effects following COVID-19 vaccination as the secondary outcomes., Methods: A systematic review with meta-analysis was performed. Searches were conducted in electronic websites, databases, and journals, including Scopus, PubMed, Embase, and Web of Science from January 01, 2019, to November 30, 2021. Studies reporting data on the safety and efficacy of COVID vaccine in cancer patients using any human samples were included. The risk of bias was assessed using the NEWCASTLE-OTTAWA scale in the included studies., Results: A total of 724 articles were identified from databases, out of which 201 articles were duplicates and were discarded. Subsequently, 454 articles were excluded through initial screening of the titles and abstracts. Moreover, 41 studies did not report the precise seroconversion rate either based on the type of cancer or after injection of a second dose of COVID vaccine. Finally, 28 articles met all the inclusion criteria and were included in this systematic review. The overall seroconversion rates after receiving a second dose of COVID-19 vaccine, based on type of cancer were 88% (95% CI, 81%-92%) and 70% (95% CI, 60%-79%) in patients with solid tumors and hematologic malignancies, respectively., Conclusion: Overall, we conclude that vaccination against COVID-19 in patients with active malignancies using activated and inactivated vaccines is a safe and tolerable procedure that is also accompanied by a high efficacy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Javadinia, Alizadeh, Mojadadi, Nikbakht, Dashti, Joudi, Harati, Welsh, Farahmand and Attarian.)

Background: Glioma is the most frequent primary brain tumor and one of the most aggressive forms of cancer. Recently, numerous studies have focused on cannabinoids as a new therapeutic approach due to their antineoplastic effects through activation of the cannabinoid receptors. This study aimed to investigate the immunohistochemical expression level of cannabinoid type-1 receptors (CB1R) in human glioma samples and evaluate its clinicopathologic significance., Materials and Methods: We analyzed the expression of CB1R in 61 paraffin-embedded glioma and 4 normal brain tissues using automated immunohistochemical assay. CB1R expression was categorized into high versus low expression levels. Statistical analyses were performed to evaluate the association between CB1R and phosphorylated extracellular signal-related kinase (p-ERK) expression levels and the clinicopathologic features of glioma., Results: Our results showed that CB1R immunopositivity was seen in 59 of 61 cases (96.7%). CB1R was down-expressed in glioma compared to normal brain tissues. However, CB1R expression was not correlated with clinicopathological parameters except for p-ERK., Conclusion: Our findings indicate the down-expression of CB1R in glioma tissues when compared to non-cancerous brain tissues. This change in CB1R expression in gliomas should be further tested regardless of the clinicopathological findings to provide a therapeutic advantage in glioma patients., (Copyright © 2022 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology.)

Alzheimer's disease (AD), acknowledged as the most common progressive neurodegenerative disorder, is the leading cause of dementia in the elderly. The characteristic pathologic hallmarks of AD-including the deposition of extracellular senile plaques (SP) formation, intracellular neurofibrillary tangles, and synaptic loss, along with prominent vascular dysfunction and cognitive impairment-have been observed in patients. Fibroblast growth factors (FGFs), originally characterized as angiogenic factors, are a large family of signaling molecules that are implicated in a wide range of biological functions in brain development, maintenance and repair, as well as in the pathogenesis of brain-related disorders including AD. Many studies have focused on the implication of FGFs in AD pathophysiology. In this review, we will provide a summary of recent findings regarding the role of FGFs and their receptors in the pathogenesis of AD, and discuss the possible opportunities for targeting these molecules as novel treatment strategies in AD., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Non-progressive dysarthria is an acquired motor speech disorder resulting from neurological diseases such as stroke and traumatic brain injury. The evidence base for the assessment of non-progressive dysarthria remains limited with professional practices relying mainly on therapists' clinical experience. Limited information on the assessment practices of Lebanese speech and language therapists (SLTs) is available. Such information is crucial for the development of adequate therapy services for clients with non-progressive dysarthria. This study aims to explore the assessment practices and attitudes of Lebanese SLTs working with adults with non-progressive dysarthria and to investigate their adherence to the framework of the World Health Organization's International Classification of Functioning, Disability and Health (ICF)., Methods: A cross-sectional study was conducted in Lebanon between March and May 2021. Data was collected through an online survey that included information on socio-demographic characteristics, practices, and attitudes of SLTs who assess adults with non-progressive dysarthria., Results: A total of 50 Lebanese SLTs responded to the survey. The majority of SLTs (78%) assessed clients with non-progressive dysarthria across all ICF domains. SLTs reported dissatisfaction with the available assessment tools (64%) and reliance on informal tools (84%). In addition, 68% of the SLTs suggested the crucial need for the development of Arabic formal assessments that can quantitatively evaluate dysarthria and determine severity. The survey also showed that the respondents demonstrated a preference for the use of impairment-based tools., Conclusion: It can be concluded that the assessment practices of Lebanese SLTs, generally, follow the international trend and the recommended professional guidelines. Further research initiatives should be held to develop Arabic formal assessment tools for non-progressive dysarthria., (© 2021. The Author(s).)

Opinion Statement: Neuroblastoma (NB) is a heterogeneous solid tumor of the pediatric population that originates from neural crest cells and affects the developing sympathetic nervous system. It is the most common neuroblastic tumor accounting for approximately 10% of all childhood cancers and 10-15% of pediatric tumor mortalities. The outcomes range from spontaneous tumor regression in low-risk groups to metastasis and death even after multimodal therapy in high-risk groups. Hence, the detection of NB at an early stage improves outcomes and provides a better prognosis for patients. Early detection and prognosis of NB depend on specific molecules termed biomarkers which can be tissue-specific or circulating. Certain biomarkers are employed in the classification of NB into different groups to improve the treatment and prognosis, and others can be used as therapeutic targets. Therefore, novel biomarker discovery is essential for the early detection of NB, predicting the course of the disease, and developing new targeted treatment strategies. In this review, we aim to summarize the literature pertinent to some important biomarkers of NB and discuss the prognostic role of these biomarkers as well as their potential role in targeted therapy., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Opinion Statement: Medulloblastoma (MB) is the most common pediatric brain malignancy, with a 5-year overall survival (OS) rate of around 65%. The conventional MB treatment, comprising surgical resection followed by irradiation and adjuvant chemotherapy, often leads to impairment in normal body functions and poor quality of life, especially with the increased risk of recurrence and subsequent development of secondary malignancies. The development and progression of MB are facilitated by a variety of immune-evading mechanisms such as the secretion of immunosuppressive molecules, activation of immunosuppressive cells, inhibition of immune checkpoint molecules, impairment of adhesive molecules, downregulation of the major histocompatibility complex (MHC) molecules, protection against apoptosis, and activation of immunosuppressive pathways. Understanding the tumor-immune relationship in MB is crucial for effective development of immune-based therapeutic strategies. In this comprehensive review, we discuss the immunological aspect of the brain, focusing on the current knowledge tackling the mechanisms of MB immune suppression and evasion. We also highlight several key immunotherapeutic approaches developed to date for the treatment of MB., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Chemokines are proinflammatory cytokines that play key roles in development of cardiovascular diseases (CVD). Chemokine-induced recruitment of peripheral leucocytes to tissues is a crucial step in the CVD progression. CC chemokines ligand 5, 2 (CCL5 and CCL2), have been characterized as emerging inflammatory biomarkers of atherosclerotic CVD. The aim of this study was to find out whether genetic polymorphisms of CCL5 -403 G>A (rs2107538) and CCL2 -927 G>C, (rs3760396) were associated with the risk of CVD., Methods: In this case-control study, 500 Iranian individuals including 250 CVD patients and 250 healthy subjects as the control group participated in 2017. Genotyping of CCL5 -403 G>A and CCL2 -927 G>C polymorphisms were executed using Tetra-ARMS PCR method., Results: At genotypic level both CCL5 -403 G>A and CCL2 -927 G>C polymorphisms were not associated with the risk of CVD ( P >0.05), even after adjustment by age, sex, race, and history of hypertension, DM and smoking. However, the CCL2 -927 C allele was associated with an increased risk of CVD (OR=1.42, P =0.050) with a higher prevalence in CVD patient than in controls (17% vs. 12%). Moreover, the haplotype analysis revealed that CCL5/CCL2 haplotype (G/C) was a risk factor for CVD (OR=2.13, P =0.001), and that carriers of this haplotype were at 2.13-fold higher risk of CVD than subjects with G/G haplotype., Conclusion: CCL2 -927 C variant and CCL5/CCL2 haplotype (G/C) were associated with susceptibility to CVD, and were risk factors for CVD in our population but more studies with large sample size are recommended., (Copyright © 2021 Mohtavinejad et al. Published by Tehran University of Medical Sciences.)

Autism spectrum disorder (ASD) is a complex and multifactorial neurodevelopmental disorder characterized by the presence of restricted interests and repetitive behaviors besides deficits in social communication. Syndromic ASD is a subset of ASD caused by underlying genetic disorders, most commonly Fragile X Syndrome (FXS) and Rett Syndrome (RTT). Various mutations and consequent malfunctions in core signaling pathways have been identified in ASD, including glycogen synthase kinase 3 (GSK3). A growing body of evidence suggests a key role of GSK3 dysregulation in the pathogenesis of ASD and its related disorders. Here, we provide a synopsis of the implication of GSK3 in ASD, FXS, and RTT as a promising therapeutic target for the treatment of ASD.

Objectives: Traumatic brain injury (TBI) represents a major health concern worldwide with a large impact in the Middle East and North Africa (MENA) region as a consequence of protracted wars and conflicts that adversely affect the general population. Currently, systematic TBI studies in the MENA region are lacking, nonetheless they are immensely needed to enhance trauma management and increase survival rates among TBI patients. This systematic review aims to characterize TBI in the MENA region to guide future policy choices and research efforts and inform tailored guidelines capable of improving TBI management and patient treatment and outcome. Furthermore, it will serve as a road map to evaluate and assess knowledge of trauma impact on regional health systems that can be adopted by health-care providers to raise awareness and improve trauma care., Methods: We conducted a comprehensive search strategy of several databases including MEDLINE/Ovid, PubMed, Embase, Scopus, CINAHL, Google Scholar, and the grey literature in accordance with the PROSPERO systematic review protocol CRD42017058952. Abstracts were screened, and selected eligible studies were reviewed independently by 2 reviewers. We collected demographics information along with TBI characteristics, mortality rates, and regional distribution. Data were extracted using REDCap and checked for accuracy., Results: The search strategy yielded 23,385 citations; 147 studies met the eligibility criteria and were included in this review. Motor vehicle accident (MVA) was the leading cause of TBI (41%) in the MENA region, followed by the military- (15.6%) and fall- (8.8%) related TBI. Males predominantly suffer from TBI-related injuries (85%), with a high prevalence of MVA- and military-related TBI injuries. The TBI mortality rate was 12.9%. The leading causes of mortality were MVA (68%), military (20.5%), and assault (2.9%). The vast majority of reported TBI severity was mild (63.1%) compared to moderate (10.7%) and severe TBI (20.2%). Patients mainly underwent a Glasgow Coma Scale assessment (22.1%), followed by computed tomography scan (8.9%) and surgery (4.1%)., Conclusions: Despite its clinical, social, and economic burden, the evidence of TBI research in the MENA region is scarce. Further research and high-quality epidemiological studies are urgently needed to gain a deep understanding of the TBI burden in the region, facilitate the allocation of adequate resources, implement effective preventive and intervention strategies and advise on the TBI patient management as reflective on the TBI patterns and modes., (© 2021 S. Karger AG, Basel.)

The gut microbiome has been shown to influence the response of tumors to anti-PD-1 (programmed cell death-1) immunotherapy in preclinical mouse models and observational patient cohorts. However, modulation of gut microbiota in cancer patients has not been investigated in clinical trials. In this study, we performed a phase 1 clinical trial to assess the safety and feasibility of fecal microbiota transplantation (FMT) and reinduction of anti-PD-1 immunotherapy in 10 patients with anti-PD-1-refractory metastatic melanoma. We observed clinical responses in three patients, including two partial responses and one complete response. Notably, treatment with FMT was associated with favorable changes in immune cell infiltrates and gene expression profiles in both the gut lamina propria and the tumor microenvironment. These early findings have implications for modulating the gut microbiota in cancer treatment., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Background: Glioblastoma multiforme (GBM), a stage IV astrocytoma, is the most common brain malignancy among adults. Conventional treatments of surgical resection followed by radio and/or chemotherapy fail to completely eradicate the tumor. Resistance to the currently available therapies is mainly attributed to a subpopulation of cancer stem cells (CSCs) present within the tumor bulk that self-renew leading to tumor relapse with time. Therefore, identification of characteristic markers specific to these cells is crucial for the development of targeted therapies. Glycogen synthase kinase 3 (GSK-3), a serine-threonine kinase, is deregulated in a wide range of diseases, including cancer. In GBM, GSK-3β is overexpressed and its suppression in vitro has been shown to induce apoptosis of cancer cells., Methods: In our study, we assessed the effect of GSK-3β inhibition with Tideglusib (TDG), an irreversible non-ATP competitive inhibitor, using two human GBM cell lines, U-251 MG and U-118 MG. In addition, we combined TDG with radiotherapy to assess whether this inhibition enhances the effect of standard treatment., Results: Our results showed that TDG significantly reduced cell proliferation, cell viability, and migration of both GBM cell lines in a dose- and time-dependent manner in vitro. Treatment with TDG alone and in combination with radiation significantly decreased the colony formation of U-251 MG cells and the sphere formation of both cell lines, by targeting and reducing their glioblastoma cancer stem-like cells (GSCs) population. Finally, cells treated with TDG showed an increased level of unrepaired radio-induced DNA damage and, thus, became sensitized toward radiation., Conclusions: In conclusion, TDG has proven its effectiveness in targeting the cancerous properties of GBM in vitro and may, hence, serve as a potential adjuvant radio-therapeutic agent to better target this deadly tumor.

Background: Neuroblastoma (NB) is the most frequently diagnosed extracranial solid tumor among the pediatric population. It is an embryonic tumor with high relapse rates pertaining to the presence of dormant slowly dividing cancer stem cells (CSC) within the tumor bulk that are responsible for therapy resistance. Therefore, there is a dire need to develop new therapeutic approaches that specifically target NB CSCs. Glycogen synthase kinase (GSK)-3β is a serine/threonine kinase that represents a common signaling node at the intersection of many pathways implicated in NB CSCs. GSK-3β sustains the survival and maintenance of CSCs and renders them insensitive to chemotherapeutic agents and radiation., Methods: In our study, we aimed at evaluating the potential anti-tumor effect of Tideglusib (TDG), an irreversible GSK-3β inhibitor drug, on three human NB cell lines, SK-N-SH, SH-SY5Y, and IMR-32., Results: Our results showed that TDG significantly reduced cell proliferation, viability, and migration of the NB cells, in a dose- and time-dependent manner, and also significantly hindered the neurospheres formation eradicating the self-renewal ability of highly resistant CSCs. Besides, TDG potently reduced CD133 cancer stem cell marker expression in both SH-SY5Y cells and G1 spheres. Lastly, TDG inhibited NB tumor growth and progression in vivo., Conclusion: Collectively, we concluded that TDG could serve as an effective treatment capable of targeting the NB CSCs and hence overcoming therapy resistance. Yet, future studies are warranted to further investigate its potential role in NB and decipher the subcellular and molecular mechanisms underlying this role.

Urmia Lake is the largest lake in the Middle East which has greatly decreased in recent years. It has had a great impact on the environmental properties of areas around the lake. This study aimed to identify the relationship among dust storms in the eastern part of Urmia Lake and the surrounding vegetation due to the annual and long-term variability of this water zone during the statistical period 1999-2019. Normalized difference water index (NDWI), normalized difference vegetation index (NDVI), Aerosol Optical Depth (AOD), and Dust Storm Index (DSI) were used due to trend and correlation analysis models and T-student analysis. The study results found that, first, the decreasing trend of Urmia Lake, directly and significantly, has led to an increase in dust concentration (AOD) in the lake's eastern part. On the other hand, changes in the water level of Lake Urmia have led to a general decreasing trend in vegetation in the region which led to an increase in the frequency of DSI in the region. The model developed showed that changes in the water zone of Urmia Lake as a very powerful driver leads to an increase in the intensity and frequency of dust storms in the eastern part of the lake and intensifies the dust conditions in the region. The synergistic resultant of these two drivers was maximized in years when both lake area and vegetation were at a minimum at the same time (2011-2016). The estimated scenario of this model is that if the decreasing trend of Urmia Lake intensifies in the study area, more frequent and severe dust storms will occur in the region.

Opinion Statement: Medulloblastoma is the most frequently diagnosed primary malignant brain tumor among children. Currently available therapeutic strategies are based on surgical resection, chemotherapy, and/or radiotherapy. However, majority of patients quickly develop therapeutic resistance and are often left with long-term therapy-related side effects and sequelae. Therefore, there remains a dire need to develop more effective therapeutics to overcome the acquired resistance to currently available therapies. Unfortunately, the process of developing novel anti-neoplastic drugs from bench to bedside is highly time-consuming and very expensive. A wide range of drugs that are already in clinical use for treating non-cancerous diseases might commonly target tumor-associated signaling pathways as well and hence be of interest in treating different cancers. This is referred to as drug repurposing or repositioning. In medulloblastoma, drug repurposing has recently gained a remarkable interest as an alternative therapy to overcome therapy resistance, wherein existing non-tumor drugs are being tested for their potential anti-neoplastic effects outside the scope of their original use.

Molecular interactions in dough are poorly defined but affect final product usage. By monitoring changes in torque as dough is formed, we identified 80-85 °C as a gateway stage determining dough collapse during the mixing/heating process. We propose that this phenomenon is a diagnostic signature linked to integral features of dough complexes formed by some wheat varieties but not others. We found the dough at 80-85 °C was stabilized by increasing the starting bowl temperature (before a standard linear increase in temperature) of the mixing process and demonstrated the significance of specific macromolecular interactions that are formed early in the mixing process. Enzymes including papain, alpha-amylase, glucose oxidase and phytase stabilized dough structure to facilitate transition through the gateway temperatures between 80 and 85 °C. Our results show that if the dough initially formed a protein-starch complex that was too large, instability and collapse of the structure can occur later., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Gliomas are a group of diseases arising from intracranial neoplastic tissues that produce a wide spectrum of clinicopathological features and morphological changes. Key questions that intrigue neuro-oncology researchers include defining novel oncophenotypic signatures relevant to diagnosing such tumors and predicting prognoses among patients. One of the key regulators of the cellular actin dynamics is adenylyl cyclase-associated protein 2 (CAP2), a protein that has been studied before in the milieu of cancer and shown to be associated with tumor progression; yet, its expression levels in the context of gliomas have not been assessed. Hence, we were interested in investigating CAP2 expression in gliomas and evaluating its clinicopathological and prognostic significance., Materials and Methods: CAP2 expression at the protein level was analyzed in 47 human paraffin-embedded gliomas and normal brain tissues by automated immunohistochemical analysis. Statistical analysis was also performed to assess CAP2 expression level in normal and tumor tissues, and to evaluate its clinicopathological and prognostic significance., Results: Our results revealed high expression of CAP2 protein in tumors of gliomas compared to normal tissues and normal areas adjacent to tumors. High expression of CAP2 was also associated with advanced tumor grades among gliomas. Kaplan-Meier analysis revealed that high CAP2 expression was associated with poor prognosis of patients with glioma (P < 0.05). In Cox regression analysis, CAP2 expression was indicated as an independent prognostic factor for overall survival (hazard ratio (HR) = 1.843, 95% confidence interval (CI), 1.252-2.714; P < 0.005)., Conclusion: CAP2 is overexpressed in glioma and it is proposed as a potential prognostic biomarker for patients with gliomas. CAP2 expression level may serve as a promising target for diagnosis and treatment of glioma., (© 2020 The Author(s).)

Objective: CLN3 disease is the commonest of the neuronal ceroid lipofuscinoses, a group of pediatric neurodegenerative disorders. Functions of the CLN3 protein include antiapoptotic properties and facilitating anterograde transport of galactosylceramide from Golgi to lipid rafts. This study confirms the beneficial effects of long-term exogenous galactosylceramide supplementation on longevity, neurobehavioral parameters, neuronal cell counts, astrogliosis, and diminution in brain and serum ceramide levels in Cln3 Δex7/8 knock-in mice. Additionally, the impact of galactosylceramide on ceramide synthesis enzymes is documented., Methods: A group of 72 mice received galactosylceramide or vehicle for 40 weeks. The effect of galactosylceramide supplementation on Cln3 Δex7/8 mice was determined by performing behavioral tests, measuring ceramide in brains and serum, and assessing impact on longevity, subunit C storage, astrogliosis, and neuronal cell counts., Results: Galactosylceramide resulted in enhanced grip strength of forelimbs in male and female mice, better balance on the accelerating rotarod in females, and improved motor coordination during pole climbing in male mice. Brain and serum ceramide levels as well as apoptosis rates were lower in galactosylceramide-treated Cln3 Δex7/8 mice. Galactosylceramide also increased neuronal cell counts significantly in male and female mice and tended to decrease subunit C storage in specific brain regions. Astrogliosis dropped in females compared to a slight increase in males after galactosylceramide. Galactosylceramide increased the lifespan of affected mice., Interpretation: Galactosylceramide improved behavioral, neuropathological, and biochemical parameters in Cln3 Δex7/8 mice, paving the way for effective therapy for CLN3 disease and use of serum ceramide as a potential biomarker to track impact of therapies. ANN NEUROL 2019;86:729-742., (© 2019 American Neurological Association.)

Aims/hypothesis: Several epidemiological studies have shown an increased risk of atrial fibrillation in individuals with type 2 diabetes or milder forms of dysglycaemia. We aimed to assess whether this relation is causal using a Mendelian randomisation approach., Methods: Two-sample Mendelian randomisation was used to obtain estimates of the influence of type 2 diabetes, fasting blood glucose (FBG), and HbA 1c on the risk of atrial fibrillation. Instrumental variables were constructed using available summary statistics from meta-analyses of genome-wide association studies (GWAS) for type 2 diabetes and associated phenotypes. Pleiotropic SNPs were excluded from the analyses. The most recent GWAS meta-analysis summary statistics for atrial fibrillation, which included over 1 million individuals (approximately 60,000 individuals with atrial fibrillation) was used for outcome analysis., Results: Neither type 2 diabetes (OR 1.01 [95% CI 0.98, 1.03]; p = 0.37), nor FBG (OR 0.95 [95% CI 0.82, 1.09] per mmol/l; p = 0.49) or HbA 1c (OR 1.01 [95% CI, 0.85, 1.17] per mmol/mol [%]; p = 0.88) were associated with atrial fibrillation in Mendelian randomisation analyses. We had >80% statistical power to detect ORs of 1.08, 1.06 and 1.09 or larger for type 2 diabetes, FBG and HbA 1c , respectively, for associations with atrial fibrillation., Conclusions/interpretation: This Mendelian randomisation analysis does not support a causal role of clinical significance between genetically programmed type 2 diabetes, FBG or HbA 1c and development of atrial fibrillation. These data suggest that drug treatment to reduce dysglycaemia is unlikely to be an effective strategy for atrial fibrillation prevention., Data Availability: The datasets analysed during the current study are available from the following repository: Nielsen JB, Thorolfsdottir RB, Fritsche LG, et al (2018) GWAS summary statistics for AF (N=60,620 AF cases and 970,216 controls). Center for Statistical Genetics: http://csg.sph.umich.edu/willer/public/afib2018/nielsen-thorolfsdottir-willer-NG2018-AFib-gwas-summary-statistics.tbl.gz.