Molecular Pathology of Laminopathies Shin, Ji-Yeon; Worman, Howard J
Annual review of pathology,
01/2022, Letnik:
17, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The nuclear envelope is composed of the nuclear membranes, nuclear lamina, and nuclear pore complexes. Laminopathies are diseases caused by mutations in genes encoding protein components of the ...lamina and these other nuclear envelope substructures. Mutations in the single gene encoding lamin A and C, which are expressed in most differentiated somatic cells, cause diseases affecting striated muscle, adipose tissue, peripheral nerve, and multiple systems with features of accelerated aging. Mutations in genes encoding other nuclear envelope proteins also cause an array of diseases that selectively affect different tissues or organs. In some instances, the molecular and cellular consequences of laminopathy-causing mutations are known. However, even when these are understood, mechanisms explaining specific tissue or organ pathology remain enigmatic. Current mechanistic hypotheses focus on how alterations in the nuclear envelope may affect gene expression, including via the regulation of signaling pathways, or cellular mechanics, including responses to mechanical stress.
Burnout is a form of negative emotional and physical response to job stress. This study aimed to investigate the prevalence of burnout among healthcare workers responding to the coronavirus disease ...2019 (COVID-19) outbreak in Korea and to explore correlates of burnout among healthcare workers. A nationwide questionnaire-based survey was conducted from December 1, 2020, to January 29, 2021 on 1425 healthcare workers who worked in one of the 16 healthcare facilities designated for COVID-19 care, in public health centers, or as paramedics in Korea. Burnout was assessed using 16 Korean-adapted items based on the Oldenburg Burnout Inventory (OLBI). Data were collected using a structured questionnaire and analyzed using the R version 4.1.1 software program. OLBI results indicate clinically exhaustion in 84.5% (1204/1425) and clinically disengagement in 91.1% (1298/1425), and 77.3% (1102/1425) met the score criteria for both the exhaustion and disengagement subscales for burnout. Burnout rate was significantly increased in the group with chronic fatigue symptoms (Fatigue Severity Scale ≥ 3.22) after the outbreak of COVID-19 (OR, 3.94; 95% CI 2.80-5.56), in the female group (OR, 2.05; 95% CI 1.46-2.86), in the group with physical symptoms (Patient Health Questionnaire-15 ≥ 10) after the outbreak of COVID-19 (OR, 2.03; 95% CI 1.14-3.60), in the group with a higher Global Assessment of Recent Stress scale (OR, 1.71; 95% CI 1.46-2.01), in the group with post-traumatic stress symptoms (Primary Care Post-Traumatic Stress Disorder-5 ≥ 2) (OR, 1.47; 95% CI 1.08-2.01), and in the younger age group(OR, 1.45; 95% CI 1.22-1.72). The chronic fatigue symptoms were correlated with cumulative days of care (OR, 1.18; 95% CI 1.02-1.37). The physical symptoms were correlated with average contact hours with COVID-19 patients per day (OR, 1.34; 95% CI 1.17-1.54), and cumulative days of care (OR, 1.21; 95% CI 1.06-1.38). Most Korean healthcare workers suffered from burnout related to excessive workload during the COVID-19 pandemic. During a widespread health crisis like COVID-19, it is necessary to regularly check the burnout status in healthcare workers and reduce their excessive workload by supplementing the workforce and providing appropriate working hours sufficient rest hours.
Polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC)/polyethylene glycol (PEG) hydrogel scaffolds are synthesized using cyclic freezing/thawing and subsequent γ‐ray irradiation to evaluate the ...effect of the molecular weights of PEG (200, 400, 1,000, and 2,000) on strength and cell growth behavior of the hydrogels. As the PEG weight increases from 200 to 2,000, the compressive strength and the pore size decreases gradually from 58.0 ± 8.2 kPa to 17.7 ± 6.1 kPa and from 22.7 ± 3.9 μm to 8.5 ± 1.6 μm, respectively. However, the highest swelling rate is obtained for PVA/CMC/PEG400 hydrogels. The irradiated PVA/CMC/PEG400 hydrogels exhibit tailored properties of the swelling rate of 1,148 ± 34.0%, the compressive strength of 42.5 ± 6.6 kPa, the pore size of 14.6 ± 1.9 μm, and cell viability of 184%. In addition, the fastest L‐929 cell proliferation and growth with time, verified by the cell proliferation (0–48 hr) and the scratch assay (0–15 hr), was observed for the PVA/CMC/PEG400 hydrogels, indicating that they are highly suitable for potential wound dressings that require fast healing regeneration.
The wound healing assay is a standard in vitro technique for probing collective cell migration in two dimensions. CC represents L‐929 cells only containing culture medium. The PVA/CMC/PEG hydrogels soaked with culture medium are designated as 200, 400, 1000, and 2000, respectively, depending on PEG molecular weight. The scratch assay of the PVA/CMC/PEG scaffolds suggests that the fastest cell migration into the cell‐free area is observed for the PVA/CMC/PEG400 hydrogel after 12 h.
The paravertebral spread that occurs after erector spinae plane block may be volume-dependent. This cadaveric study was undertaken to compare the extent of paravertebral spread with erector spinae ...plane block using different dye volumes. After randomization, twelve erector spinae plane blocks were performed bilaterally with either 10 ml or 30 ml of dye at the level of T5 in seven unembalmed cadavers except for two cases of unexpected pleural puncture using the 10 ml injection. Direct visualization of the paravertebral space by endoscopy was performed immediately after the injections. The back regions were also dissected, and dye spread and nerve involvement were investigated. A total of five 10 ml injections and seven 30 ml injections were completed for both endoscopic and anatomical evaluations. No paravertebral spread was observed by endoscopy after any of the 10-ml injections. Dye spread to spinal nerves at the intervertebral foramen was identified by endoscopy at adjacent levels of T5 (median: three levels) in all 30 ml injections. In contrast, the cases with two, four, and three out of five were stained at only the T4, T5, and T6 levels, respectively, with the 10 ml injection. Upon anatomical dissection, all blocks were consistently associated with posterior and lateral spread to back muscles and fascial layers, especially with the 30 ml injections, which showed greater dye expansion. In one 30 ml injection, sympathetic nerve involvement and epidural spread were observed at the level of the injection site. Although paravertebral spread following erector spinae plane block increased in a volume-dependent manner, this increase was variable and not pronounced. As the injectate volume increased for the erector spinae blocks, the injectate spread to the back muscles and fascial layers seemed to be predominantly increased compared with, the extent of paravertebral spread.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This study analyzed the Korea National Health and Nutrition Examination Survey data from 2007 to 2017 to assess trends in prevalence, treatment, and control of diabetes in Korean adults ≥30 years of ...age.
Prevalent diabetes was defined as fasting plasma glucose level ≥ 126 mg/dl, self-reported use of antidiabetic treatment (insulin or oral anti-diabetic drugs), or diabetes diagnosis by a physician. Target levels were defined as glycosylated hemoglobin <6.5% or <7.0%, blood pressure <130/80 mmHg, and total cholesterol <200 mg/dl. All survey waves were age-standardized to the 2005 Korean census population.
Diabetes prevalence increased from 9.6% in 2007-2009 to 10.8% in 2016-2017 (p<0.001). Impaired fasting glucose prevalence significantly increased in both sexes and almost every age group. Diabetes awareness and glycemic control did not show an increasing trend; however, the treatment rate and proportion of people diagnosed with diabetes achieving blood pressure and total cholesterol target levels improved from 57.2% to 63.5% (p=0.008), from 41.1% to 53.2% (p<0.001), and from 65.0% to 78.0% (p<0.001), respectively.
From 2007 to 2017, the prevalence of diabetes increased moderately in Korea whereas the diabetes treatment rates as well as the proportion of people diagnosed with diabetes achieving blood pressure and total cholesterol target levels improved. However, awareness of diabetes and the levels of glycemic control all require significant improvements. A national-level action plan is required to raise awareness about diabetes and prediabetes towards improving glycemic control and minimizing the occurrence of adverse health outcomes.
To elucidate the effects of neoadjuvant chemotherapy (NAC), we conduct whole transcriptome profiling coupled with histopathology analyses of a longitudinal breast cancer cohort of 146 patients ...including 110 pairs of serial tumor biopsies collected before treatment, after the first cycle of treatment and at the time of surgery. Here, we show that cytotoxic chemotherapies induce dynamic changes in the tumor immune microenvironment that vary by subtype and pathologic response. Just one cycle of treatment induces an immune stimulatory microenvironment harboring more tumor infiltrating lymphocytes (TILs) and up-regulation of inflammatory signatures predictive of response to anti-PD1 therapies while residual tumors are immune suppressed at end-of-treatment compared to the baseline. Increases in TILs and CD8+ T cell proportions in response to NAC are independently associated with pathologic complete response. Further, on-treatment immune response is more predictive of treatment outcome than immune features in paired baseline samples although these are strongly correlated.
(MAB) is one of the rapidly growing, multidrug-resistant non-tuberculous mycobacteria (NTM) causing various diseases including pulmonary disorder. Although it has been known that type I interferons ...(IFNs) contribute to host defense against bacterial infections, the role of type I IFNs against MAB infection is still unclear. In the present study, we show that rIFN-β treatment reduced the intracellular growth of MAB in macrophages. Deficiency of IFN-α/β receptor (IFNAR) led to the reduction of nitric oxide (NO) production in MAB-infected macrophages. Consistently, rIFN-β treatment enhanced the expression of iNOS gene and protein, and NO production in response to MAB. We also found that NO is essential for the intracellular growth control of MAB within macrophages in an inhibitor assay using iNOS-deficient cells. In addition, pretreatment of rIFN-β before MAB infection in mice increased production of NO in the lungs at day 1 after infection and promoted the bacterial clearance at day 5. However, when alveolar macrophages were depleted by treatment of clodronate liposome, rIFN-β did not promote the bacterial clearance in the lungs. Moreover, we found that a cytosolic receptor nucleotide-binding oligomerization domain 2 (NOD2) is required for MAB-induced TANK binding kinase 1 (TBK1) phosphorylation and IFN-β gene expression in macrophages. Finally, increase in the bacterial loads caused by reduction of NO levels was reversed by rIFN-β treatment in the lungs of NOD2-deficient mice. Collectively, our findings suggest that type I IFNs act as an intermediator of NOD2-induced NO production in macrophages and thus contribute to host defense against MAB infection.
Objective
MicroRNAs (miRNAs) regulate gene expression and have many roles in the brain, but a role in oligodendrocyte (OL) function has not been demonstrated.
Methods
A Dicer floxed conditional ...allele was crossed with the proteolipid protein promoter‐driven inducible Cre allele to generate inducible, OL‐specific Dicer‐floxed mice.
Results
OL‐specific Dicer mutants show demyelination, oxidative damage, inflammatory astrocytosis and microgliosis in the brain, and eventually neuronal degeneration and shorter lifespan. miR‐219 and its target ELOVL7 (elongation of very long chain fatty acids protein 7) were identified as the main molecular components that are involved in the development of the phenotype in these mice. Overexpressing ELOVL7 results in lipid accumulation, which is suppressed by miR‐219 co‐overexpression. In Dicer mutant brain, excess lipids accumulate in myelin‐rich brain regions, and the peroxisomal β‐oxidation activity is dramatically reduced.
Interpretation
Postnatal Dicer ablation in mature OLs results in inflammatory neuronal degeneration through increased demyelination, lipid accumulation, and peroxisomal and oxidative damage, and therefore indicates that miRNAs play an essential role in the maintenance of lipids and redox homeostasis in mature OLs that are necessary for supporting axonal integrity as well as the formation of compact myelin. Ann Neurol 2009;66:843–857
The gut microbiota, which includes Akkermansia muciniphila, is known to modulate energy metabolism, glucose tolerance, immune system maturation and function in humans
. Although A. muciniphila is ...correlated with metabolic diseases and its beneficial causal effects were reported on host metabolism
, the molecular mechanisms involved have not been identified. Here, we report that A. muciniphila increases thermogenesis and glucagon-like peptide-1 (GLP-1) secretion in high-fat-diet (HFD)-induced C57BL/6J mice by induction of uncoupling protein 1 in brown adipose tissue and systemic GLP-1 secretion. We apply fast protein liquid chromatography and liquid chromatography coupled to mass spectrophotometry analysis to identify an 84 kDa protein, named P9, that is secreted by A. muciniphila. Using L cells and mice fed on an HFD, we show that purified P9 alone is sufficient to induce GLP-1 secretion and brown adipose tissue thermogenesis. Using ligand-receptor capture analysis, we find that P9 interacts with intercellular adhesion molecule 2 (ICAM-2). Interleukin-6 deficiency abrogates the effects of P9 in glucose homeostasis and downregulates ICAM-2 expression. Our results show that the interactions between P9 and ICAM-2 could be targeted by therapeutics for metabolic diseases.
Background
Massage and aromatherapy massage are used to relieve cancer‐related symptoms. A number of claims have been made for these treatments including reduction of pain, anxiety, depression, and ...stress. Other studies have not shown these benefits.
Objectives
To evaluate the effects of massage with or without aromatherapy on pain and other symptoms associated with cancer.
Search methods
We searched the following databases and trials registries up to August 2015: the Cochrane Central Register of Controlled Trials (CENTRAL, 2015, Issue 7), MEDLINE (Ovid), EMBASE (Ovid), PsycINFO (Ovid), CINAHL (EBSCO), PubMed Cancer Subset, SADCCT, and the World Health Organization (WHO) ICTRP. We also searched clinical trial registries for ongoing studies.
Selection criteria
Randomised controlled studies (RCTs) reporting the effects of aromatherapy or massage therapy, or both, in people with cancer of any age. We applied no language restrictions. Comparators were massage (using carrier oil only) versus no massage, massage with aromatherapy (using carrier oil plus essential oils) versus no massage, and massage with aromatherapy (using carrier oil plus essential oils) versus massage without aromatherapy (using carrier oil only).
Data collection and analysis
At least two review authors selected studies, assessed the risk of bias, and extracted data relating to pain and other symptoms associated with cancer, using standardised forms. We assessed the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) and created two 'Summary of findings' tables.
Main results
We included 19 studies (21 reports) of very low quality evidence with a total of 1274 participants. We included 14 studies (16 reports) in a qualitative synthesis and five studies in a quantitative synthesis (meta‐analysis). Thirteen studies (14 reports, 596 participants) compared massage with no massage. Six studies (seven reports, 561 participants) compared aromatherapy massage with no massage. Two studies (117 participants) compared massage with aromatherapy and massage without aromatherapy. Fourteen studies had a high risk of bias related to sample size and 15 studies had a low risk of bias for blinding the outcome assessment. We judged the studies to be at unclear risk of bias overall. Our primary outcomes were pain and psychological symptoms. Two studies reported physical distress, rash, and general malaise as adverse events. The remaining 17 studies did not report adverse events. We downgraded the GRADE quality of evidence for all outcomes to very low because of observed imprecision, indirectness, imbalance between groups in many studies, and limitations of study design.
Massage versus no‐massage groups
We analysed results for pain and anxiety but the quality of evidence was very low as most studies were small and considered at an unclear or high risk of bias due to poor reporting. Short‐term pain (Present Pain Intensity‐Visual Analogue Scale) was greater for the massage group compared with the no‐massage group (one RCT, n = 72, mean difference (MD) ‐1.60, 95% confidence interval (CI) ‐2.67 to ‐0.53). Data for anxiety (State‐Trait Anxiety Inventory‐state) relief showed no significant difference in anxiety between the groups (three RCTs, n = 98, combined MD ‐5.36, 95% CI ‐16.06 to 5.34). The subgroup analysis for anxiety revealed that the anxiety relief for children was greater for the massage group compared with the no‐massage group (one RCT, n = 30, MD ‐14.70, 95% CI ‐19.33 to ‐10.07), but the size of this effect was considered not clinically significant. Furthermore, this review demonstrated no differences in effects of massage on depression, mood disturbance, psychological distress, nausea, fatigue, physical symptom distress, or quality of life when compared with no massage.
Massage with aromatherapy versus no‐massage groups
We analysed results for pain, anxiety, symptoms relating to the breast, and quality of life but the quality of evidence was very low as studies were generally at a high risk of bias. There was some indication of benefit in the aromatherapy‐massage group but this benefit is unlikely to translate into clinical benefit. The relief of medium‐ and long‐term pain (medium‐term: one RCT, n = 86, MD 5.30, 95% CI 1.52 to 9.08; long‐term: one RCT, n = 86, MD 3.80, 95% CI 0.19 to 7.41), anxiety (two RCTs, n = 253, combined MD ‐4.50, 95% CI ‐7.70 to ‐1.30), and long‐term symptoms relating to the breast in people with breast cancer (one RCT, n = 86, MD ‐9.80, 95% CI ‐19.13 to ‐0.47) was greater for the aromatherapy‐massage group, but the results were considered not clinically significant. The medium‐term quality of life score was lower (better) for the aromatherapy‐massage group compared with the no‐massage group (one RCT, n = 30, MD ‐2.00, 95% CI ‐3.46 to ‐0.54).
Massage with aromatherapy versus massage without aromatherapy groups
From the limited evidence available, we were unable to assess the effect of adding aromatherapy to massage on the relief of pain, psychological symptoms including anxiety and depression, physical symptom distress, or quality of life.
Authors' conclusions
There was a lack of evidence on the clinical effectiveness of massage for symptom relief in people with cancer. Most studies were too small to be reliable and key outcomes were not reported. Any further studies of aromatherapy and massage will need to address these concerns.
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