BACKGROUND Music performance is a highly stressful activity, requiring skilled neuromuscular dexterity. A lack of reported strategies for musicians suffering performance-related musculoskeletal disorders (PRMDs) exists. Papers investigating the role that postural distortions or spinal structural anomalies that could play a role in setting the stage for PRMD do not exist. The purpose of this paper was to provide a description and discussion of the use of a specialized upper cervical manual correction at the cranio-cervical junction (CCJ) to treat a violist who had disabling pain in her wrists, arms, neck, and hip. Differential diagnoses are required regarding possible confounding elements within the cervical spine. CASE REPORT After 40 years of music performance, a violist experienced severe pain while attempting to play the simplest student musical pieces. Early retirement seemed imminent. To determine appropriate chiropractic approach, the patient's clinical assessment included active range of motion, chiropractic tests, palpation, and radiographic study. Postural distortions, hypertonic muscles, joint pain, arthritis, and ponticulus posticus (PP) were noted. Upper cervical spine orthogonal radiographic series were used to develop a correction strategy. These images identified excursion of the cervical spine away from the vertical axis and C0-C1-C2 misalignments. After performing low-velocity, low-force manual correction to the CCJ, the patient experienced immediate relief of wrist pain. Over a 9-month follow-up period, the patient reported gradual decrease of pain and increased stamina while performing. Upon completing chiropractic care, the violist's career was restored. CONCLUSIONS This case supports the hypothesis that evaluating and correcting spinal structures proximal to painful extremities may represent an efficient and long-lasting solution for PRMD.BACKGROUND Mini-chromosome maintenance families (MCMs) were considered the key factors for DNA replication initiation. Emerging evidences indicate that MCM2-7 (MCMs) are highly expressed in tissues from various malignant tumors. However, little is known about the clinical values of MCMs in breast cancer. MATERIAL AND METHODS In our study, a comprehensive bioinformatics analysis was performed to investigate expression patterns, potential functions, and prognostic values of MCMs in breast cancer, through ONCOMINE, **-GenExMiner v4.1, Kaplan-Meier Plotter, cBioPortal and GeneMANIA databases. RESULTS We found that mRNA levels of MCMs were significantly elevated in breast cancer, especially in fast-growing and spreading tumor subtypes. These over-expressed MCMs predicted worse prognosis for breast cancer patients with shorter relapse-free survival (RFS) and overall survival. Among these six factors, high expression of MCM2/4/5/7 significantly reduced the RFS for patients with Luminal-A or B breast cancer and elevated MCM6/7 indicated shorter RFS for patients with basal-like or HER2-positive breast cancer. We also found that genomic alteration of MCMs was frequently found in breast cancer and the most common alteration was mRNA upregulation and amplification. Furthermore, MCMs were highly correlated with CDC45, CDC7, TIMELESS, ORC6, MCM10, ORC5, ORC4 and ORC3, mainly functioning to control the DNA replication initiation and genome stability. CONCLUSIONS These results suggest that MCMs are attractive prognostic biomarkers for breast cancer. Our study also provides useful clinical information about the potential of MCMs as therapeutic targets.BACKGROUND Fractional exhaled nitric oxide (FENO) has emerged as a promising marker in respiratory research. The aim of this study was to determine the reference range values of FENO for healthy Saudi adults and the factors associated with FENO levels. MATERIAL AND METHODS This cross-sectional study was conducted at the Department of Physiology, King Saud University, Riyadh, Saudi Arabia, from January 2016 to August 2017. A total of 429 healthy Saudi adults were initially recruited. The final selection included 412 participants, consisting of 307 men and 105 women. https://www.selleckchem.com/products/nicotinamide-riboside-chloride.html FENO measurements were performed according to the current recommendations of the American Thoracic Society. RESULTS We observed that the FENO levels of women were significantly lower than those of men (18.6 vs. 21.3, P=0.009). In women, the measured FENO ranged from 5.7 ppb to 42 ppb, and in men from 5.0 ppb to 55.0 ppb. The mean FENO level in the entire study population was 20.6, with a range of 5.0 ppb to 55.0 ppb. The difference became non-significant when we calculated the FENO after adjusting for body surface area by different percentile distributions. Multiple linear regression analysis showed that body surface area and weight were significant predictors of FENO levels. CONCLUSIONS In this study, FENO levels were significantly affected by demographic variables. Therefore, it is important to consider the factors influencing FENO values to make a valid clinical interpretation.Flavonoids have diverse biological functions in human health. All flavonoids contain a common 2-phenyl chromone structure (C6-C3-C6) as a scaffold. Hence, in using such a scaffold, plenty of highvalue-added flavonoids can be synthesized by chemical or biological catalyzation approaches. (2S)-Naringenin is one of the most commonly used flavonoid scaffolds. However, biosynthesizing (2S)-naringenin has been restricted not only by low production but also by the expensive precursors and inducers that are used. Herein, we established an induction-free system to de novo biosynthesize (2S)-naringenin in Escherichia coli. The tyrosine synthesis pathway was enhanced by overexpressing feedback inhibition-resistant genes (aroGfbr and tyrAfbr) and knocking out a repressor gene (tyrR). After optimizing the fermentation medium and conditions, we found that glycerol, glucose, fatty acids, potassium acetate, temperature, and initial pH are important for producing (2S)-naringenin. Using the optimum fermentation medium and conditions, our best strain, Nar-17LM1, could produce 588 mg/l (2S)-naringenin from glucose in a 5-L bioreactor, the highest titer reported to date in E. coli.
BACKGROUND Music performance is a highly stressful activity, requiring skilled neuromuscular dexterity. A lack of reported strategies for musicians suffering performance-related musculoskeletal disorders (PRMDs) exists. Papers investigating the role that postural distortions or spinal structural anomalies that could play a role in setting the stage for PRMD do not exist. The purpose of this paper was to provide a description and discussion of the use of a specialized upper cervical manual correction at the cranio-cervical junction (CCJ) to treat a violist who had disabling pain in her wrists, arms, neck, and hip. Differential diagnoses are required regarding possible confounding elements within the cervical spine. CASE REPORT After 40 years of music performance, a violist experienced severe pain while attempting to play the simplest student musical pieces. Early retirement seemed imminent. To determine appropriate chiropractic approach, the patient's clinical assessment included active range of motion, chiropractic tests, palpation, and radiographic study. Postural distortions, hypertonic muscles, joint pain, arthritis, and ponticulus posticus (PP) were noted. Upper cervical spine orthogonal radiographic series were used to develop a correction strategy. These images identified excursion of the cervical spine away from the vertical axis and C0-C1-C2 misalignments. After performing low-velocity, low-force manual correction to the CCJ, the patient experienced immediate relief of wrist pain. Over a 9-month follow-up period, the patient reported gradual decrease of pain and increased stamina while performing. Upon completing chiropractic care, the violist's career was restored. CONCLUSIONS This case supports the hypothesis that evaluating and correcting spinal structures proximal to painful extremities may represent an efficient and long-lasting solution for PRMD.BACKGROUND Mini-chromosome maintenance families (MCMs) were considered the key factors for DNA replication initiation. Emerging evidences indicate that MCM2-7 (MCMs) are highly expressed in tissues from various malignant tumors. However, little is known about the clinical values of MCMs in breast cancer. MATERIAL AND METHODS In our study, a comprehensive bioinformatics analysis was performed to investigate expression patterns, potential functions, and prognostic values of MCMs in breast cancer, through ONCOMINE, bc-GenExMiner v4.1, Kaplan-Meier Plotter, cBioPortal and GeneMANIA databases. RESULTS We found that mRNA levels of MCMs were significantly elevated in breast cancer, especially in fast-growing and spreading tumor subtypes. These over-expressed MCMs predicted worse prognosis for breast cancer patients with shorter relapse-free survival (RFS) and overall survival. Among these six factors, high expression of MCM2/4/5/7 significantly reduced the RFS for patients with Luminal-A or B breast cancer and elevated MCM6/7 indicated shorter RFS for patients with basal-like or HER2-positive breast cancer. We also found that genomic alteration of MCMs was frequently found in breast cancer and the most common alteration was mRNA upregulation and amplification. Furthermore, MCMs were highly correlated with CDC45, CDC7, TIMELESS, ORC6, MCM10, ORC5, ORC4 and ORC3, mainly functioning to control the DNA replication initiation and genome stability. CONCLUSIONS These results suggest that MCMs are attractive prognostic biomarkers for breast cancer. Our study also provides useful clinical information about the potential of MCMs as therapeutic targets.BACKGROUND Fractional exhaled nitric oxide (FENO) has emerged as a promising marker in respiratory research. The aim of this study was to determine the reference range values of FENO for healthy Saudi adults and the factors associated with FENO levels. MATERIAL AND METHODS This cross-sectional study was conducted at the Department of Physiology, King Saud University, Riyadh, Saudi Arabia, from January 2016 to August 2017. A total of 429 healthy Saudi adults were initially recruited. The final selection included 412 participants, consisting of 307 men and 105 women. https://www.selleckchem.com/products/nicotinamide-riboside-chloride.html FENO measurements were performed according to the current recommendations of the American Thoracic Society. RESULTS We observed that the FENO levels of women were significantly lower than those of men (18.6 vs. 21.3, P=0.009). In women, the measured FENO ranged from 5.7 ppb to 42 ppb, and in men from 5.0 ppb to 55.0 ppb. The mean FENO level in the entire study population was 20.6, with a range of 5.0 ppb to 55.0 ppb. The difference became non-significant when we calculated the FENO after adjusting for body surface area by different percentile distributions. Multiple linear regression analysis showed that body surface area and weight were significant predictors of FENO levels. CONCLUSIONS In this study, FENO levels were significantly affected by demographic variables. Therefore, it is important to consider the factors influencing FENO values to make a valid clinical interpretation.Flavonoids have diverse biological functions in human health. All flavonoids contain a common 2-phenyl chromone structure (C6-C3-C6) as a scaffold. Hence, in using such a scaffold, plenty of highvalue-added flavonoids can be synthesized by chemical or biological catalyzation approaches. (2S)-Naringenin is one of the most commonly used flavonoid scaffolds. However, biosynthesizing (2S)-naringenin has been restricted not only by low production but also by the expensive precursors and inducers that are used. Herein, we established an induction-free system to de novo biosynthesize (2S)-naringenin in Escherichia coli. The tyrosine synthesis pathway was enhanced by overexpressing feedback inhibition-resistant genes (aroGfbr and tyrAfbr) and knocking out a repressor gene (tyrR). After optimizing the fermentation medium and conditions, we found that glycerol, glucose, fatty acids, potassium acetate, temperature, and initial pH are important for producing (2S)-naringenin. Using the optimum fermentation medium and conditions, our best strain, Nar-17LM1, could produce 588 mg/l (2S)-naringenin from glucose in a 5-L bioreactor, the highest titer reported to date in E. coli.
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