Cordycepin induces apoptosis of human ovarian cancer cells by inhibiting CCL5-mediated Akt/NF-κB signaling pathway

The chemokine, CCL5, is a key mediator for the recruitment of immune cells into tumors and tissues. Akt/NF-κB signaling is significantly activated by CCL5. However, the role of NF-κB inactivation in apoptosis induced by negative regulation of CCL5 remains unclear. Here, we analyzed the effect of cordycepin on NF-κB activity in SKOV-3 cells and found that cordycepin-mediated inhibition of NF-κB signaling induced apoptosis in SKOV-3 cells via the serial activation of caspases. In addition, immune-blotting analysis showed that CCL5 is highly expressed in SKOV-3 cells. In addition to activating caspases, we show that, cordycepin prevents TNF-α-induced increase in CCL5, Akt, NF-κB, and c-FLIPL activation and that CCL5 siRNA could inhibit Akt/NF-κB signaling. Moreover, cordycepin negatively regulated the TNF-α-mediated IκB/NF-κB pathway and c-FLIPL activation to promote JNK phosphorylation, resulting in caspase-3 activation and apoptosis. Also, we show that c-FLIPL is rapidly lost in NF-κB activation-deficient. siRNA mediated c-FLIP inhibition increased JNK. SP600125, a selective JNK inhibitor, downregulated p-JNK expression in cordycepin-treated SKOV-3 cells, leading to suppression of cordycepin-induced apoptosis. Thus, these results indicate that cordycepin inhibits CCL5-mediated Akt/NF-κB signaling, which upregulates caspase-3 activation in SKOV-3 cells, supporting the potential of cordycepin as a therapeutic agent for ovarian cancer

The genetic architecture of type 2 diabetes

The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of heritability. To test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole genome sequencing in 2,657 Europeans with and without diabetes, and exome sequencing in a total of 12,940 subjects from five ancestral groups. To increase statistical power, we expanded sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support a major role for lower-frequency variants in predisposition to type 2 diabetes

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Evaluation of the <i>forAge</i> Age-at-Death Estimation Program Using Pubic Symphyseal Surface in a Korean Population

The forAge program estimates the age-at-death of human pubic symphysis using 3-dimensional scans. It was developed by Dennis E. Slice and Bridget F. B. Algee-Hewitt, and utilizes three distinct scores: the Slice and Algee-Hewitt (SAH) score, bending energy (BE), and ventral curvature (VC). However, these scores and age estimation regression equation were obtained through European American pubic symphysis. Changes in the pubic symphysis surface are evaluated as one of the most reliable indicators for estimating age, but in connection with this, using Korean materials, changes in the pubic symphysis surface and the actual changes are evaluated. There is no bar where the relationship between ages is grasped, and there are cases where a methodology developed for a specific group is applied to a Korean group. Changing the pubic symphysis surface by aging was evaluated as one of the most reliable indicators for estimating age. However, there is no study conducted on the relationship between changes in the pubic symphysis and actual age and applied the age estimation method for a specific population among Korean population. The purpose of this study is to compare the difference between the actual age and the estimated age in Korean to see if the forAge program is applicable to other population of different ancestral origin. One hundred and four modern Korean pubic symphyseal surfaces (47 to 96 years old) were used in this study. Through the pubic symphyseal surface 3-dimensional images, age-at-death was estimated via prediction equation and new regression lines using SAH, VC, and BE scores. Firstly, the estimated age via prediction equation using the first version of SAH score was lower than the actual age according to all pubic symphyseal surfaces for those older than 56. With aging, the difference between the actual age and estimated age became markedly larger. Secondly, the estimated ages via the new regression lines using VC, the second version of SAH score, and BE were shown a similar pattern to the previous prediction equation. The current study explored the applicability of a quantitative method using pubic symphyseal surface for age estimation in a modern Korean population. This study showed the forAge program cannot be applied to a modern Korean population, as they present relatively low correlations with the actual age-at-death

Effective Locations for Injecting Botulinum Toxin into the Mentalis Muscle; Cadaveric and Ultrasonographic Study

The mentalis muscle is now considered key structures when performing procedures for rejuvenating the lower face. The aim of this study was to determine the anatomical morphology and location of the mentalis muscle and thereby provide anatomical information for facilitating clinical procedures designed to rejuvenate the lower face. Forty-four adult hemifaces from five Thai cadavers and 21 Korean cadavers were dissected to identify the locations of the mentalis muscle. Sixty-six hemifaces from 33 healthy young Korean subjects were included in an ultrasonographic study. The depth of the mentalis muscle below the skin surface, the thickness of the mentalis muscle, and the distance from the bone to the mentalis muscle were measured at the two points that were 5 mm lateral to the most-prominent point of the chin. The mentalis muscle was classified into two types based to its shape: in type A (86.4%, 38 of the 44 cases) it was dome shaped in three dimensions, while in type B (13.6%, 6 of the 44 cases) it was flat. The mentalis muscle was present mostly at the area 5–10 mm from the midsagittal line and 20–30 mm from a horizontal line connecting the mouth corners. The mentalis muscle was present between depths of 6.7 to 10.7 mm below the skin. This new information about the location of the mentalis muscle may help when identifying the most effective and safe botulinum toxin injection points and depths during esthetic procedures for weakened facial rhytides on the lower face

Effective Locations for Injecting Botulinum Toxin into the Mentalis Muscle; Cadaveric and Ultrasonographic Study

The mentalis muscle is now considered key structures when performing procedures for rejuvenating the lower face. The aim of this study was to determine the anatomical morphology and location of the mentalis muscle and thereby provide anatomical information for facilitating clinical procedures designed to rejuvenate the lower face. Forty-four adult hemifaces from five Thai cadavers and 21 Korean cadavers were dissected to identify the locations of the mentalis muscle. Sixty-six hemifaces from 33 healthy young Korean subjects were included in an ultrasonographic study. The depth of the mentalis muscle below the skin surface, the thickness of the mentalis muscle, and the distance from the bone to the mentalis muscle were measured at the two points that were 5 mm lateral to the most-prominent point of the chin. The mentalis muscle was classified into two types based to its shape: in type A (86.4%, 38 of the 44 cases) it was dome shaped in three dimensions, while in type B (13.6%, 6 of the 44 cases) it was flat. The mentalis muscle was present mostly at the area 5–10 mm from the midsagittal line and 20–30 mm from a horizontal line connecting the mouth corners. The mentalis muscle was present between depths of 6.7 to 10.7 mm below the skin. This new information about the location of the mentalis muscle may help when identifying the most effective and safe botulinum toxin injection points and depths during esthetic procedures for weakened facial rhytides on the lower face

Topographic Relationship between the Supratrochlear Nerve and Corrugator Supercilii Muscle—Can This Anatomical Knowledge Improve the Response to Botulinum Toxin Injections in Chronic Migraine?

Chronic migraine has been related to the entrapment of the supratrochlear nerve within the corrugator supercilii muscle. Recently, research has shown that people who have undergone botulinum neurotoxin A injection in frontal regions reported disappearance or alleviation of their migraines. There have been numerous anatomical studies conducted on Caucasians revealing possible anatomical problems leading to migraine; on the other hand, relatively few anatomical studies have been conducted on Asians. Thus, the aim of the present study was to determine the topographic relationship between the supratrochlear nerve and corrugator supercilii muscle in the forehead that may be the cause of migraine. Fifty-eight hemifaces from Korean and Thai cadavers were used for this study. The supratrochlear nerve entered the corrugator supercilii muscle in every case. Type I, in which the supratrochlear nerve emerged separately from the supraorbital nerve at the medial one-third portion of the orbit, was observed in 69% (40/58) of cases. Type II, in which the supratrochlear nerve emerged from the orbit at the same location as the supraorbital nerve, was observed in 31% (18/58) of cases