PAMAM dendrimers based co-delivery of methotrexate and berberine for targeting of Hela cancer cells.

Polyamidoamine dendrimer (PAMAM) is a class of synthetic macromolecular polymers for targeted drug delivery. PAMAM dendrimers are characterized by a pure defined structure, adjustable nanoscale dimensions, mono-dispersity, and versatile surface modification. The objective of this study was to study the covalent coupling of methotrexate (MTX) to PAMAM dendrimer, which was loaded with the natural product anticancer agent, berberine (BER) for the targeting of HeLa cells. The successful preparation of MTX-conjugated PAMAM loaded with BER (MTX-PAMAM-BER) was confirmed by Fourier transform infrared spectroscopy and particle size was evaluated using dynamic light scattering. The biological assays, MTT, flow cytometry, ROS levels evaluation and DAPI staining were used to assess the cytotoxicity effect of the prepared nanosystem. The findings indicated that MTX-PAMAM-BER exhibited greater suppression of tumor cell growth in comparison to BER, MTX, PAMAM-BER, and MTX-PAMAM. Besides, the noteworthy ROS level has been seen in the treated cells with MTX-PAMAM-BER. Finally, it should be stated that the fabricated MTX-PAMAM-BER co-delivery nanosystem could be a promising agent for cancer therapy and targeting.

The Effects of Crocus sativus (Saffron) on ADHD: A Systematic Review.

BACKGROUND AND AIM: Crocus sativus also known as saffron, is one of the most popular traditional plants. This study aims to evaluate the efficacy and safety of saffron extracts in ADHD. METHOD: This study includes clinical trial studies that assessed the efficacy and/or safety of saffron in ADHD patients. Non-English papers, review articles, commentaries, letters, observational studies, thesis, animal studies, in-vitro studies, and conference abstracts were not included. The risk of bias in randomized studies was evaluated based on the Cochrane RoB.2, and risk of bias in pre-post intervention studies was assessed using the ROBINS-I tool. RESULTS: Four studies met our inclusion criteria with a total of 118 patients. The results manifested an efficient role of saffron as either an adjuvant therapy to MPH or a single therapy against ADHD, without significant safety issues. DISCUSSION: Saffron demonstrates promise in improving ADHD symptoms, with an acceptable safety profile. Future well-designed multicentral studies are suggested.

Berberine-induced glucagon-like peptide-1 and its mechanism for controlling type 2 diabetes mellitus: a comprehensive pathway review.

Introduction: A growing number of studies have thus far showed the association between type 2 diabetes mellitus (DM) and the intestinal microbiome homoeostasis. As reported, the gut microflora can be significantly different in patients with type 2 DM (T2DM) compared to those in healthy individuals.Methods: The authors collected the relevant articles published until 2022 and these are carefully selected from three scientific databases based on keywords.Discussion: This review highlights research on the anti-diabetic properties of berberine (BBR)-induced glucagon-like peptide-1 (GLP-1), as a glucose-lowering factor and a balance regulator in the microbial flora of the intestines, which plays an important role in adjusting the signalling pathways affecting insulin secretion.Results: Considering the anti-diabetic characteristics of the BBR-induced GLP-1, BBR makes a promising complementary treatment for reducing the clinical symptoms of DM by reducing the hyperglycaemia. Berberin might be a safe and effective drug for T2DM with little or no adverse effects.HighlightsBerberine induces GLP-1 insulin secretion by PLC2 pathway in the intestinalBerberine-induced GLP-1 decreases mitochondrial stress and relocates cytochrome c out of the mitochondria.Berberine induces GLP-1 secretion in the intestine by altering the bacterial profile, thus could possibly lighten diabetes symptomsBerberine-induced SCFA production, SCFA causes GLP-1 secretion from the intestinal L-Cell.Preventing mitochondrial damage, reducing adipose tissue fat, and reducing oxidative stress are thus among the results of BBR-induced GLP-1.The lower costs of BBR, and its limited side effects and higher availability, make it a promising supplementary medicine for DM.

The effects of olive oil consumption on cognitive performance: a systematic review.

Introduction: The Mediterranean diet is marked by the regular intake of olive oil, which may play a role in preventing and protecting against cognitive deterioration and dementia. The strength of these effects have been examined by several recent randomized controlled trials (RCTs), but their findings have not been consistent. In light of this inconsistency, the present study performed a systematic review to examine the relationship between the consumption of olive oil and cognition. Methods: The Web of Science, Scopus, PubMed, and Google Scholar were systematically searched up to August 11, 2023. The review included RCTs, cross-sectional studies, cohort studies and case-control studies that explored the impact of olive oil consumption on cognitive performance among those older than 55 years old. Studies were excluded if they employed a design other than those mentioned above, involved participants under 55 years old, or did not specifically examine the cognitive effects of olive oil consumption. The quality of the included studies were measured using the Cochrane risk-of-bias tool and the Newcastle Ottawa Scale checklists. Results: Eleven studies were identified, which were comprised of four cross-sectional studies, four prospective cohort studies and three RCTs. The cohort studies and RCTs consistently found that olive oil consumption had a favorable effect on cognitive performance across a number of cognitive domains over time. Similarly, all of the cross-sectional studies reported that the consumption of olive oil was positively associated with cognitive health. Conclusion: The consumption of olive oil was found to enhance cognitive functioning and to reduce cognitive decline. Further large-scale investigations are required to strengthen this conclusion.

The burden of Alzheimer's disease and other types of dementia in the Middle East and North Africa region, 1990-2019.

BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia and this progressive neurological disorder is associated with substantial mortality and morbidity. We aimed to report the burden of AD and other types of dementia in the Middle East and North Africa (MENA) region, by age, sex and sociodemographic index (SDI), for the period 1990-2019. METHODS: publicly accessible data on the prevalence, death and disability-adjusted life years (DALYs) because of AD, and other types of dementia, were retrieved from the global burden of disease 2019 project for all MENA countries from 1990 to 2019. RESULTS: in 2019, the age-standardised point prevalence of dementia was 777.6 per 100,000 populations in MENA, which was 3.0% higher than in 1990. The age-standardised death and DALY rates of dementia were 25.5 and 387.0 per 100,000, respectively. In 2019, the highest DALY rate was observed in Afghanistan and the lowest rate was in Egypt. That same year, the age-standardised point prevalence, death and DALY rates increased with advancing age and were higher for females of all age groups. From 1990 to 2019, the DALY rate of dementia decreased with increasing SDI up to 0.4, then slightly increased up to an SDI of 0.75, followed by a decrease for the remaining SDI levels. CONCLUSIONS: the point prevalence of AD and other types of dementia has increased over the past three decades, and in 2019, the corresponding regional burden was higher than the global average.

The effect of cognitive-behavioral counseling with or without Citrus aurantium essential oil on sleep quality in pregnant women: a randomized controlled trial.

Sleep disorder is very common during pregnancy. Non-pharmacological treatments are a priority to improve the sleep pattern. This study aimed to determine the effect of cognitive-behavioral counseling with or without Citrus aurantium essential oil on sleep quality (primary outcome) and anxiety and quality of life (secondary outcomes). This randomized controlled trial was performed on 75 pregnant women in Tabriz, Iran. Participants were randomly assigned to the intervention and control groups. The first intervention group received 8 sessions of cognitive-behavioral counseling and aromatherapy with Citrus aurantium essential oil 15-20 min before bedtime. The second intervention group received cognitive-behavioral counseling and aromatherapy with placebo and the control group received only routine prenatal care. Pittsburgh Sleep Quality Index, Pregnancy-Specific Quality of life Questionnaire, and Pregnancy-Specific Anxiety Scale were completed before and after intervention. After the intervention based on ANCOVA test and by adjusting the baseline score, the mean score of anxiety in the intervention group 1 (AMD: - 4.54; 95% CI - 6.79 to - 2.28) and intervention group 2 (AMD: - 3.30; 95% CI - 5.60 to - 0.97) was significantly lower than the control group. Also, the mean score of quality of life in intervention group 1 (AMD: 2.55; 95% CI 0.45-4.65) and intervention group 2 (AMD: 2.72; 95% CI 0.60-4.83) was significantly higher than the control group, but there was no statistically significant difference between the study groups in terms of sleep quality (P > 0.05). Also, there was no statistically significant difference between the two intervention groups after the intervention in terms of anxiety (P = 0.379) and quality of life (P = 0.996). Cognitive-behavioral counseling reduced anxiety and improved quality of life. However, further trials are required to reach a definitive conclusion. Iranian Registry of Clinical Trials (IRCT): IRCT20120718010324N63. Date of registration: 4/10/2020. URL: https://en.irct.ir/user/trial/54986/view; Date of first registration: 18/10/2020.

The burden of Parkinson's disease in the Middle East and North Africa region, 1990-2019: results from the global burden of disease study 2019.

BACKGROUND: Parkinson's disease (PD) remains a common disabling progressive neurodegenerative disorder. We aimed to report the prevalence, death and disability-adjusted life-years (DALYs) attributable to PD in the Middle East and North Africa (MENA) region and its 21 countries by age, sex and socio-demographic index (SDI), between 1990 and 2019. METHODS: Publicly available data on the burden of PD in the MENA countries were retrieved from the Global Burden of Disease (GBD) 2019 project. The results are presented with age-standardised numbers and rates per 100,000 population, along with their corresponding 95% uncertainty intervals (UIs). RESULTS: In 2019, PD had an age-standardised point prevalence of 82.6 per 100,000 population in MENA and an age-standardised death rate of 5.3, which have increased from 1990 to 2019 by 15.4% and 2.3%, respectively. In 2019, the age-standardised DALY rate of PD was 84.4, which was 0.9% higher than in 1990. The highest and lowest age-standardised DALY rates of PD in 2019 were found in Qatar and Kuwait, respectively. Also in 2019, the highest number of prevalent cases and number of DALYs were found in the 75-79 age group for both sexes. In 2019, females in MENA had an overall higher DALY rate. Furthermore, from 1990 to 2019 the burden of PD generally decreased with increasing socio-economic development, up to an SDI of around 0.4, and then increased with higher levels of SDI. CONCLUSION: An upward trend was observed in the point prevalence of PD over the last three decades. This highlights the need to allocate more resources for research. Furthermore, properly equipped healthcare services are needed for the increasing number of patients with PD.

Evidence for Hesperidin as an Effective Factor in Initiating the Intrinsic Pathway of Apoptosis in KG1a Leukemia Cells.

Acute myeloid leukemia (AML) is the most common subtype of leukemia, accounting for 62% of all leukemia fatalities. As a polyphenol glycoside, hesperidin triggers the apoptotic pathway, which might positively affect combating cancer cells. In this study, we investigated the pro-apoptotic effects of hesperidin in KG1a cells. The MTT assay was used to determine the IC50 of hesperidin in KG1a cell lines. For the apoptotic cell morphology study, we used Hoechst 33 258 staining. Activation of the caspase-3 enzyme was evaluated by the caspase-3 assay and spectrophotometry. Cell cycle distribution was analyzed by propidium iodide staining and flow cytometry. Moreover, p21, survivin, Bax, and Bcl2 gene expression was investigated by real-time PCR. Hesperidin decreased the viability of KG1a leukemic cell4s, but not that of HFF2, a non-cancer cell line. Apoptotic cell morphological alterations and increase in caspase-3 activity were observed after hesperidin treatment. Our results revealed that the expression of anti-apoptotic genes survivin and Bcl2 significantly decreased with hesperidin treatment, and pro-apoptotic gene Bax and cell cycle regulator p21 increased compared to the control group. These findings revealed that hesperidin may be an effective factor in initiating the intrinsic pathway of apoptosis and may be good candidate for the treatment of AML.

The effect of Salvia officinalis on blood glycemic indexes and blood lipid profile in diabetic patients: a systematic review and meta-analysis.

Diabetes is one of the most common endocrine disorders that increases the economic burden on the public health system. In this regard, understanding the effect of available herbs on diabetes can be useful. This systematic review was performed to determine the effect of Salvia officinalis on blood glycemic indexes and blood lipid profile (primary outcomes) and 2 h postprandial blood glucose (2HPPG), alanine transaminase (ALT) (U/L) and aspartate transaminase (AST) (U/L) and its side effects (secondary outcomes) in diabetic patients. A systematic search was conducted in the English (Cochrane Library, Medline (PubMed), Scopus, CINAHL, ProQuest and Persian databases since inception to March 2021, without publication time restriction. Two authors separately evaluated the quality of the articles using Cochrane Collaboration's tool for assessing the risk of bias in randomized trials and extracted the data. Heterogeneity of data was evaluated by squared I (I 2). Three studies included in the review and all of them included in meta-analysis. The results of meta-analysis showed that S. officinalis reduced fasting blood sugar (FBS) (mg/dL) (MD: -31.15; 95% CI: -37.56 to -24.73; p<0.00001). It also reduced HbA1c (%) (MD: -0.94; 95% CI: -1.25 to -0.63; p<0.00001) and total cholesterol (mg/dL) (MD: -43.64; 95% CI: -83.26 to -4.02; p=0.03) and reduction of low-density protein (LDL) (mg/dL) (MD: -19.23; 95% CI: -35.81 to -2.65; p=0.02) but it did not have a significant effect on triglyceride (mg/dL) (p=0.09), and high-density lipoprotein (HDL) (mg/dL) (p=0.18). Regarding the secondary outcomes, S. officinalis also had significant effect on 2HPPG, but it did not have a significant effect on ALT (U/L) and AST (U/L). No specific side effects for this plant were reported in these three studies. The results showed that S. officinalis has a positive effect on blood glycemic status and blood lipid profile in diabetes except for triglyceride and HDL. However, due to the small number of included articles, it is recommended that stronger clinical trials be conducted in this field.

Saffron as a promising therapy for diabetes and Alzheimer's disease: mechanistic insights.

The prevalence of both Alzheimer's disease (AD) and diabetes mellitus is increasing with the societies' aging and has become an essential social concern worldwide. Accumulation of amyloid plaques and neurofibrillary tangles (NFTs) of tau proteins in the brain are hallmarks of AD. Diabetes is an underlying risk factor for AD. Insulin resistance has been proposed to be involved in amyloid-beta (Aß) aggregation in the brain. It seems that diabetic conditions can result in AD pathology by setting off a cascade of processes, including inflammation, mitochondrial dysfunction, and ROS and advanced glycation end products (AGEs) synthesis. Due to the several side effects of chemical drugs and their high cost, using herbal medicine has recently attracted attention for the treatment of diabetes and AD. Saffron and its active ingredients have been used for its anti-inflammatory, anti-oxidant, anti-diabetic, and anti-AD properties. Therefore, in the present review paper, we take account of the clinical, in vivo and in vitro evidence regarding the anti-diabetic and anti-AD effects of saffron and discuss the preventive or postponing properties of saffron or its components on AD development via its anti-diabetic effects.

Effect of Citrullus colocynthis on glycemic factors and lipid profile in type II diabetic patients: a systematic review and meta-analysis.

Purpose: In this systematic review and meta-analysis, we investigated the effect and side effects of Citrullus colocynthis on glycemic factors and lipid profile in diabetic patients. Methods: We systematically searched English and Persian databases from inception till August 2021 using Medical Subject Headings (MeSH). Two authors independently extracted data and assessed the quality of studies. The standardized mean differences were pooled using fixed-effect models, and statistical heterogeneity was assessed using the I squared (I²) index. Results: Of the 321 articles searched in the databases, 136 related articles were screened, 14 relevant full-text articles were assessed for eligibility; finally, four articles were included in the study, three articles were entered into the meta-analysis. The results of the meta-analysis indicated that Citrullus colocynthis does not have a significant effect on fasting blood sugar (FBS), hemoglobin A1c (HBA1c), low-density lipoprotein (LDL), total cholesterol, and triglyceride indices but increases high-density lipoprotein (HDL) (Mean Difference: 5.76; 95% CI: 1.69 to 9.84; P = 0.006; I2 = 0%). Conclusions: The meta-analysis results showed that Citrullus colocynthis has no significant effect on glycemic and metabolic indices of diabetes - except HDL. Due to the relatively low quality and the small number of included trials, conducting further large scale well-designed randomized clinical trials to determine the effect of Citrullus colocynthis on glycemic and metabolic indices seems essential. Supplementary information: The online version contains supplementary material available at 10.1007/s40200-022-01045-9.

Profile of Tabriz Older People Health Survey (TOPS-2019): a representative community-based cross-sectional study.

Population aging and its consequences are a substantial global concern. The growth in the number of older people is one of the most important factors increasing the burden of non-communicable diseases (NCDs) on society. The Tabriz Older People Health Survey aimed to understand the socio-demographics, health-related behaviors, and health profile of older adults. This cross-sectional study was conducted on a representative sample of 1362 community-dwelling older adults in Tabriz, the most populated city in northwest Iran. The study used probability proportionate to size sampling and the data collection was undertaken in each participants' place of residence from July 2019 to January 2020. Trained interviewers administered the questionnaire, which measured each participant's socio-demographics, health-related behaviors, and health profile. The sample of 1362 participants consisted of 56.4% women and 54.4% were young older people (60-69 years old). Almost half of the sample were completely illiterate. There was no daily walking in 13.3% of the sample, with women reporting a more sedentary lifestyle than men. Almost 10% of the participants (n = 135, 9.9%) were current smokers, which was higher among men (20.9% vs. 1.5%) and women made up over 88% of those living alone. In terms of sleep quality score (men: 4.63 ± 2.70, women: 5.97 ± 2.93), anxiety (men: 5.79 ± 4.70, women: 7.59 ± 5.51), depression (men: 9.54 ± 3.20, women: 10.63 ± 3.09), and social support (men: 23.65 ± 4.50, women: 22.69 ± 4.77), men were significantly better than women. There were also significant sex differences between women and men in the prevalence of diabetes (31.6% vs. 19.5%) and hypertension (86.5% vs. 73.4%). Furthermore, overall hypertension was the most common underlying disease (81.0%). Older women were significantly worse off than older men, in terms of social and disability-related, as well as having a higher burden from several NCDs. The results of this study might help regional health policymakers to identify targets for improving the health status among community-housed geriatrics.

Burden of tension-type headache in the Middle East and North Africa region, 1990-2019.

INTRODUCTION: Tension-type headache (TTH) is the most prevalent neurological disorder. As there is a gap in the literature regarding the disease burden attributable to TTH in the Middle East and North Africa (MENA) region, the aim of the present study was to report the epidemiological indicators of TTH in MENA, from 1990 to 2019, by sex, age and socio-demographic index (SDI). METHODS: Publicly available data on the point prevalence, annual incidence and years lived with disability (YLDs) were retrieved from the global burden of disease (GBD) 2019 study for the 21 countries and territories in MENA, between 1990 and 2019. The results were presented with numbers and age-standardised rates per 100000 population, along with their corresponding 95% uncertainty intervals (UIs). RESULTS: In 2019, the age-standardised point prevalence and annual incidence rates for TTH in the MENA region were 24504.5 and 8680.1 per 100000, respectively, which represents a 2.0% and a 0.9% increase over 1990-2019, respectively. The age-standardised YLD rate of TTH in this region in 2019 was estimated to be 68.1 per 100000 population, which has increased 1.0% since 1990. Iran [29640.4] had the highest age-standardised point prevalence rate for TTH, while Turkey [21726.3] had the lowest. In 2019, the regional point prevalence of TTH was highest in the 35-39 and 70-74 age groups, for males and females, respectively. Furthermore, the number of prevalent cases was estimated to be highest in those aged 35-39 and 25-29 years, in both males and females, respectively. Moreover, the burden of TTH was not observed to have a clear association with SDI. CONCLUSIONS: While the prevalence of TTH in the MENA region increased from 1990 to 2019, the incidence rate did not change. In addition, the burden of TTH in MENA was higher than at the global level for both sexes and all age groups. Therefore, prevention of TTH would help alleviate the attributable burden imposed on the hundreds of millions of people suffering from TTH around the region.

The effect of saffron supplementation on glycemic parameters: An overview of systematic reviews.

Due to the widespread use of herbal medicine and evidence pointing to the health benefits of saffron supplementation, this review was performed to evaluate the effects of saffron supplementation on glycemic parameters and lipid profiles based on previous reviews. Relevant articles were retrieved from various databases, which included PubMed, Scopus, ProQuest, Web of Science, Embase, and Cochrane until 2020, with no date restrictions. The quality of the included reviews was assessed using the Assessment of Multiple Systematic Reviews (AMSTAR) checklist. Finally, of 877 obtained articles, eight reviews meeting the inclusion criteria were included for analysis. Among the eight included reviews, seven articles were meta-analyses. In addition, one review had an average quality while seven had a good quality. A narrative description of the included reviews was performed, while a network meta-analysis was not conducted. A brief review of the results was reported according to the weighted mean difference and mean difference. Seven included reviews assessed the effects of saffron or crocin supplementation on glycemic parameters, and six examined these effects on lipid profile parameters. Almost half of the articles reported significant effects of these supplements on glycemic parameters and lipid profiles. Taken together, results suggest that saffron supplementation may improve glycemic and lipid profile parameters; however, further high-quality studies are needed to confirm the clinical efficacy of saffron on glycemic parameters and lipid profiles.

Effects of saffron (Crocus sativus L.) on anthropometric and cardiometabolic indices in overweight and obese patients: A systematic review and meta-analysis of randomized controlled trials.

The worldwide prevalence of obesity is approximately tripled between 1975 and 2016 according to World Health Organization; therefore, obesity is now considered a global pandemic that needs academic and clinical focus. In search of antiobesity agents, Crocus sativus, known widely as saffron, has been praised for its beneficial effects. Several randomized controlled trials (RCTs) have been conducted to investigate the weight lowering effect of saffron. Following PRISMA guidelines, several medical databases were comprehensively searched for RCTs with a population consisting of obese individuals. A random-effects meta-analysis was used to pool estimates across studies, and standardized mean difference (SMD) was used to synthesize quantitative results. Twenty-five RCTs met the inclusion criteria. Meta-analysis showed a nonsignificant decrease for weight (-0.32 kg; CI: -3.15, 2.51; p = 0.82), BMI (-0.06 kg/m2 ;CI:-1.04,0.93; p = .91), waist circumference (-1.23 cm; CI: -4.14, 1.68; p = .41), and hip circumference (-0.38 cm; CI: -5.99, 5.23; p = .89) and a significant decrease of waist-to-hip ratio (SMD = -0.41; CI: -0.73, -0.09; p = .01; I2  = 0%). The mean difference in fasting blood sugar showed a significant reduction in patients with metabolic syndrome (SMD = -0.30; 95% CI: -0.63, 0.03; p = .07; I2  = 0.37%) but a nonsignificant change in the HbA1C level (WMD = 0.05; 95% CI: 0.32, 0.41; p = .79). Despite bearing several limitations, mainly as a result of heterogeneity among included studies, the available evidence indicates saffron supplementation shows promising effects on some cardiometabolic factors among overweight to obese patients; however, further investigations and high-quality evidence are required for more generalizable and comprehensive results.

Anti-diabetic potential of Urtica Dioica: current knowledge and future direction.

Aim: This review summarizes studies on the anti-diabetic effect of Urtica Dioica (UD) in Type-2-diabetes. Materials and methods: We studied worldwide traditional medicines, old texts, and published literature for anti-diabetic effect of UD. Electronic databases comprising PubMed, Web of Science, Science Direct, Scopus and Google Scholar were searched to collect articles published between 1990 and 2021 years. Results: Our literature investigation suggests UD as a glucose lowering, blood lipid regulating, anti-inflammatory and anti-oxidation plant. Conclusions: UD's anti-diabetic properties make it potential traditional therapeutics for lowering the clinical manifestations of T2DM through affecting hyperglycemia and therefore suggest it as a proper medication with no or limited side effects.

Phytochemical and pharmacological anti-diabetic properties of bilberries (Vaccinium myrtillus), recommendations for future studies.

Nowadays, extensive attention has focused on dietary constituents that may be valuable for treating, eating, and preventing diabetes. Numerous studies have shown that anthocyanin's are one of the most important nutritional factors associated with diabetes. Anthocyanin's are the leading group of water-soluble pigments in the plant kingdom, and they are generally available in some human diet in fruits, vegetables, cereals, beans. Amongst, bilberries (Vaccinium myrtillus), is one of the essential sources for dietary anthocyanin consumption containing vast amounts of anthocyanin's, making them the main plant in the treatment and prevention of diabetes. Although the bilberries have other valuable properties such as anti-cancer, anti-inflammatory, and antioxidant, the main focus of the present study is to present the effects of bilberries (V. myrtillus) on the prevention and treatment of diabetes.

Neck pain: global epidemiology, trends and risk factors.

BACKGROUND: Neck pain is one of the most common musculoskeletal disorders, having an age-standardised prevalence rate of 27.0 per 1000 population in 2019. This literature review describes the global epidemiology and trends associated with neck pain, before exploring the psychological and biological risk factors associated with the initiation and progression of neck pain. METHODS: The PubMed database and Google Scholar search engine were searched up to May 21, 2021. Studies were included that used human subjects and evaluated the effects of biological or psychological factors on the occurrence or progression of neck pain, or reported its epidemiology. RESULTS: Psychological risk factors, such as long-term stress, lack of social support, anxiety, and depression are important risk factors for neck pain. In terms of the biological risks, neck pain might occur as a consequence of certain diseases, such as neuromusculoskeletal disorders or autoimmune diseases. There is also evidence that demographic characteristics, such as age and sex, can influence the prevalence and development of neck pain, although further research is needed. CONCLUSIONS: The findings of the present study provide a comprehensive and informative overview that should be useful for the prevention, diagnosis, and management of neck pain.

Relative Strengths of Three Linearizations of Receptor Availability: Saturation, Inhibition, and Occupancy Plots.

We derived three widely used linearizations from the definition of receptor availability in molecular imaging with positron emission tomography (PET). The purpose of the present research was to determine the convergence of the results of the 3 methods in terms of 3 parameters-occupancy (s), distribution volume of the nondisplaceable reference binding compartment (VND), and nondisplaceable reference binding potential (BPND) of the radioligand-in the absence of a gold standard. We tested 104 cases culled from the literature and calculated the goodness of fit of the least-squares and Deming II methods of linear regression when applied to the determination of s, VND, and BPND using the goodness-of-fit parameters R2, coefficient of variation (root-mean-square error [RMSE]), and the infinity norm (‖X‖∞) with both regression methods. We observed superior convergence among the values of s, VND, and BPND for the inhibition and occupancy plots. The inhibition plot emerged as the plot with a slightly higher degree of convergence (based on R2, RMSE, and ‖X‖∞ value). With two regression methods (the least-squares method [LSM] and the Deming II [DM] method), the estimated values of s, VND, and BPND generally converged. The inhibition and occupancy plots yielded the best fits to the data, according to the goodness-of-fit parameters, due primarily to absence of commingling of the dependent and independent variables tested with the saturation (original Lassen) plot. In the presence of noise, the inhibition and occupancy plots yielded higher convergences.