Despite the widespread shrinkage of debris-covered Himalayan glaciers in recent decades, the underlying processes driving these changes are poorly understood. This study presents recent mass-balance ...data for the debris-covered area of Lirung Glacier in Langtang Valley, Nepal Himalaya, constrained using multi-temporal, remotely sensed digital elevation models calibrated to in situ GPS survey data, and surface-flow velocity data from phase-only correlation. The results indicate surface lowering of between −1.3 and −1.8 m a–1 during the study period (1974–2010), with accelerated glacier thinning after 2000. Similarly, we observed a decline in emergence velocity in the upper debris-covered area since 2000. We argue that this deceleration plays a key role in surface lowering, in contrast to declining surface mass balance, which we suggest is a residual effect of emergence velocity and surface lowering. Taken together, our findings indicate that the recent increase in surface lowering is attributable to the declining flux of ice from the upper to lower debris-covered areas of Lirung Glacier. Furthermore, this pattern suggests that downwasting of the upper debris-covered area will be augmented by a positive feedback between surface lowering and decelerated flow velocity.
Interstitial lung disease and cardiac involvement are common manifestations and prognostic factors of systemic sclerosis. However, it is unclear whether impaired right atrial function associated with ...interstitial lung disease in systemic sclerosis can be used as a prognostic factor in this patient population. Therefore, this study aimed to investigate the relationship between right atrial function, interstitial lung disease, and prognosis in patients with systemic sclerosis using tissue tracking analysis with cine cardiac magnetic resonance imaging. In this retrospective observational study, a total of 40 patients with systemic sclerosis were enrolled. Tissue tracking analysis was used to obtain time curves of right atrial strain. Reservoir (total strain), conduit (passive strain), and booster (active strain) pump function were calculated, and right atrial strain, interstitial lung disease, and clinical outcomes were examined. An adverse clinical event was defined as all-cause death. Overall, 23 patients had interstitial lung disease (58%). Six patients died during the follow-up (median, 44 months). The total skin score and right ventricular systolic pressure on echocardiography were higher in patients with an event than in those without an event (28 ± 16% vs. 13 ± 13%,
P
= 0.02; 46.3 ± 10.7 mmHg vs. 36.0 ± 8.5 mmHg,
P
= 0.01, respectively). Further, right atrial total strain and active strain were significantly lower in patients with an event than in those without an event (14.3 ± 11.3% vs. 25.8 ± 11.4%,
P
= 0.03; 3.48 ± 2.37 vs. 11.7 ± 6.78,
P
= 0.007, respectively). Multivariate analysis revealed that active strain was an independent predictor of all-cause death (hazard ratio 0.76,
P
= 0.029). Kaplan–Meier analysis revealed that the survival rate was significantly higher in patients with right atrial active strain levels above the cutoff 7.4 (
P
< 0.05). In systemic sclerosis, right atrial booster function was predictive of mortality. Hence, right atrial functional assessment may have incremental prognostic value for patients with systemic sclerosis, leading to better risk stratification.
There have been rapid increases in both the number and
expansion of the proglacial lakes across High Mountain Asia. However, the
relationship between proglacial lakes and glacier dynamics remains ...unclear
in the Himalayan region. Here we present the surface elevation, flow-velocity changes, and proglacial lake expansion of Thorthormi and Lugge
glaciers in the Lunana region, Bhutanese Himalaya, during the 2000–2018
period using photogrammetry and GPS survey data. The lake expansion and
surface lowering rates and flow-velocity field of Lugge Glacier, a
lake-terminating glacier, have remained approximately constant since 2000.
Conversely, there have been accelerated proglacial lake expansion and a
2-fold increase in the thinning rate of Thorthormi Glacier since 2011, as
well as a considerable speed-up in the flow-velocity field
(>150 m a−1). We reveal that the lake formation and transition of Thorthormi
Glacier from a land- to lake-terminating glacier have triggered glacier
speed-up and rapid thinning via a positive (compressive) to negative
(extensional) change in the emergence velocities. This study provides the
first evidence of dynamic glacier changes that are associated with
proglacial lake formation across the Himalayan region.
ABSTRACT
Aims/Introduction
Metabolic dysfunction‐associated fatty liver disease (MAFLD), defined as hepatosteatosis with type 2 diabetes mellitus, overweight/obesity or metabolic dysregulation, has ...been proposed as a new feature of chronic liver disease. Fatty acid‐binding protein 4 (FABP4) is expressed in adipose tissue, and secreted FABP4 is associated with the development of insulin resistance and atherosclerosis. However, the relationship between MAFLD and FABP4 has not been fully addressed.
Materials and Methods
Associations of MAFLD with metabolic markers, including FABP4, fibroblast growth factor 21 and adiponectin, were investigated in 627 individuals (men/women 292/335) in the Tanno‐Sobetsu Study, a population‐based cohort.
Results
The mean age was 65 years (range 19–98 years, median interquartile range 68 56–76 years). Hepatosteatosis was determined by the fatty liver index (FLI), and FLI ≥35 for men and FLI ≥16 for women were used for detection of fatty liver, as previously reported using 14,471 Japanese individuals. FLI was positively correlated with systolic blood pressure and levels of FABP4 (r = 0.331, P < 0.001), fibroblast growth factor 21, homeostasis model assessment of insulin resistance as an insulin resistance index and uric acid, and was negatively correlated with levels of high‐density lipoprotein cholesterol and adiponectin. FABP4 concentration was independently associated with FLI after adjustment of age, sex, systolic blood pressure and levels of uric acid, high‐density lipoprotein cholesterol, homeostasis model assessment of insulin resistance, adiponectin and fibroblast growth factor 21 in multivariable regression analysis. Logistic regression analysis showed that FABP4 was an independent predictor of MAFLD after adjustment of age, sex, presence of diabetes mellitus, hypertension and dyslipidemia, and levels of uric acid, homeostasis model assessment of insulin resistance, adiponectin and fibroblast growth factor 21.
Conclusions
FABP4 concentration is independently associated with FLI and is an independent predictor of MAFLD in middle‐aged and elderly individuals.
Metabolic dysfunction‐associated fatty liver disease, defined as hepatosteatosis with overweight/obesity, presence of type 2 diabetes mellitus or evidence of metabolic dysregulation, has been proposed as a new feature of chronic liver disease. Fatty acid‐binding protein 4 concentration is independently associated with the fatty liver index and is an independent predictor of metabolic dysfunction‐associated fatty liver disease in a general population.
Aim: Dyslipidemia and altered iron metabolism are typical features of non-alcoholic fatty liver disease (NAFLD). Proprotein convertase subtilisin/kexin type 7 (PCSK7), a transmembrane-anchored ...endonuclease, is associated with triglycerides level and processing of transferrin receptor 1. However, the significance of circulating PCSK7 has not been fully addressed, though prosegment PCSK7 is secreted from cells. We investigated the associations of plasma PCSK7 level with several parameters. Methods: Plasma PCSK7 concentration was measured in 282 subjects (male/female: 126/156) without medication of the Tanno-Sobetsu Study, a population-based cohort study. Results: There was no significant sex difference in PCSK7 level. Current smoking habit, but not alcohol drinking habit, was associated with increased PCSK7 level. PCSK7 concentration was negatively correlated with age and blood urea nitrogen and was positively correlated with body mass index (BMI) and levels of γ-glutamyl transpeptidase (γGTP), triglycerides and fatty liver index (FLI), which is calculated by BMI, waist circumference and levels of γGTP and triglycerides, as a noninvasive and simple predictor of NAFLD. There were no significant correlations of PCSK7 level with levels of iron and plasma PCSK9, a secreted PCSK family member and a regulator of low-density lipoprotein cholesterol level. Multivariable regression analyses after adjustment of age, sex and current smoking habit showed that PCSK7 concentration was independently associated with BMI (β=0.130, P=0.035), triglycerides (β=0.141, P=0.027) or FLI (β=0.139, P=0.030).Conclusions: Plasma PCSK7 concentration is independently associated with chronic liver disease including obesity and elevated triglycerides level in a general population of individuals who had not regularly taken any medications.
Changes in chromatin composition accompany cellular differentiation in eukaryotes. Although bulk chromatin is duplicated during DNA replication, replication-independent (RI) nucleosome replacement ...occurs in transcriptionally active chromatin and during specific developmental transitions where the genome is repackaged
1, 2. In most animals, replacement uses the conserved H3.3 histone variant
3, but the functions of this variant have not been defined. Using mutations for the two H3.3 genes in
Drosophila, we identify widespread transcriptional defects in H3.3-deficient animals. We show that mutant animals compensate for the lack of H3.3 in two ways: they upregulate the expression of the major histone H3 genes, and they maintain chromatin structure by using H3 protein for RI nucleosome replacement at active genes. Rescue experiments show that increased expression of H3 is sufficient to relieve transcriptional defects. In contrast, H3.3 is essential for male fertility, and germline cells specifically require the histone variant. Defects without H3.3 first occur around meiosis, resulting in a failure to condense, segregate, and reorganize chromatin. Rescue experiments with mutated transgenes demonstrate that H3.3-specific residues involved in RI nucleosome assembly—but not major histone modification sites—are required for male fertility. Our results imply that the H3.3 variant plays an essential role in chromatin transitions in the male germline.
We quantify the surface elevation changes along Yala Glacier in Langtang Valley, Nepal Himalaya, since 1981 using geodetic methods to understand the recent evolution and current state of small ...debris-free glaciers across the region. We analyse differential global positioning system measurements and aerial stereo imagery that were acquired along Yala Glacier in 2007, 2009, 2012 and 2015 to generate digital elevation models for each calculation period. Continuous surface lowering has mainly been observed across the down-glacier area during the calculation periods, although a large degree of variability exists, with this lowering trend propagating up-glacier in recent years. The area-weighted glacier mass balances range from −0.98 ± 0.27 to −0.26 ± 0.30 m w.e. a−1 for the five calculation periods (1981–2007, 2007–2009, 2009–2012, 2012–2015 and 2007–2015). These calculated mass-balance data reveal that Yala Glacier has undergone accelerated mass loss since the late 2000s, which is consistent with the results of previous in situ measurement and remote-sensing studies.
Background: The saphenous vein (SV) is used as an essential conduit in coronary artery bypass grafting (CABG), but the long-term patency of SV grafts is a crucial issue. The use of the novel ...“no-touch” technique of harvesting the SV together with its surrounding tissue has been reported to result in good long-term graft patency of SV grafts. We recently showed that perivascular adipose tissue (PVAT) surrounding the SV (SV-PVAT) had lower levels of metaflammation and consecutive adipose tissue remodeling than did PVAT surrounding the coronary artery. However, the difference between SV-PVAT and subcutaneous adipose tissue (SCAT) remains unclear.Methods and Results: Fat pads were sampled from 55 patients (38 men, 17 women; mean ±SD age 71±8 years) with coronary artery disease who underwent elective CABG. Adipocyte size was significantly larger in SV-PVAT than SCAT. The extent of fibrosis was smaller in SV-PVAT than SCAT. There were no significant differences between SCAT and SV-PVAT in macrophage infiltration area, quantified by antibodies for CD68, CD11c, and CD206, or in gene expression levels of metaflammation-related markers. Expression patterns of adipocyte developmental and pattern-forming genes differed between SCAT and SV-PVAT.Conclusions: The properties of SV-PVAT are close to, but not the same as, those of SCAT, possibly resulting from inherent differences in adipocytes. SV-PVAT has healthy expansion with less fibrosis in fat than SCAT.
Objectives
Myocardial flow reserve (MFR), derived from ammonia N-13 positron emission tomography (NH
3
-PET), can predict the prognosis of patients with various heart diseases. We aimed to ...investigate whether myocardial strain ratio (MSR) was useful in predicting MACE and allowed for further risk stratification of cardiovascular events in patients with ischemic heart disease (IHD) in addition to MFR.
Methods
Ninety-five patients underwent NH
3
-PET because of IHD. MFR was determined as the ratio of hyperemic to resting myocardial blood flow (MBF). MSR was defined as the ratio of strains at stress and rest. The endpoint was major adverse cardiac events (MACE), including all-cause death, acute coronary syndrome, heart failure hospitalization, and revascularization. The ability to predict MACE was assessed using receiver operating characteristic (ROC) analysis, and the predictability of ME was analyzed using Kaplan–Meier analysis. The Cox proportional hazards regression model was used to calculate the hazard ratio (HR) with 95% confidence interval (CI).
Results
The ROC curve analysis demonstrated a cutoff of 0.93 for MACE with MSR (sensitivity and specificity of 77% and 71%, respectively). Patients with MSR < 0.93 displayed a significantly higher MACE rate than those with MSR ≥ 0.93 (
p
= 0.0036). The Cox proportional hazards regression analysis indicated that MSR was an independent marker that could predict MACE in imaging and clinical parameters (HR, 7.32; 95% CI: 1.59–33.7,
p
= 0.011).
Conclusions
MSR was an independent predictor of MACE and was useful for further risk stratification in IHD. MSR has the potential for a new indicator of revascularization in patients with IHD.
Key Points
• We hypothesized that combining myocardial flow reserve (MFR) with the myocardial strain ratio (MSR) obtained by applying the feature-tracking technique to ammonia N-13 PET would make it predictive of major adverse cardiac events (MACE) compared to MFR alone.
• MSR was an independent predictor of MACE, allowing for further risk stratification in addition to MFR in patients with ischemic heart disease.
• MSR is a potential new indicator of revascularization.
Coronary computed tomography angiography (CCTA) has low specificity for detecting significant functional coronary stenosis. We developed a new transluminal attenuation gradient (TAG)-derived dynamic ...CCTA with dose modulation, and we investigated its diagnostic performance for myocardial ischemia depicted by
13
N-ammonia positron emission tomography (PET). Data from 48 consecutive patients who had undergone both dynamic CCTA and
13
N-ammonia PET were retrospectively analyzed. Dynamic CCTA was continuously performed in mid-diastole for five cardiac cycles with prospective electrocardiography gating after a 10-s contrast medium injection. One scan of the dynamic CCTA was performed as a boost scan for conventional CCTA at the peak phase of the ascending aorta. Absolute TAG values at five phases around the boost scan were calculated. The dynamic TAG index (DTI) was defined as the ratio of the maximum absolute TAG to the standard deviation of five TAG values. We categorized the coronary territories as non-ischemia or ischemia based on the
13
N-ammonia PET results. A receiver operating characteristic (ROC) analysis was performed to determine the optimal cutoff of the DTI for identifying ischemia. The DTI was significantly higher for ischemia compared to non-ischemia (8.8 ± 3.9 vs. 4.6 ± 2.0,
p
< 0.01). The ROC analysis revealed 5.60 as the optimal DTI cutoff to detect ischemia, with an area under the curve of 0.87, 85.7% sensitivity, and 76.2% specificity. TAG provided no additional diagnostic value for the detection of ischemia. We propose the DTI derived from dynamic CCTA as a novel coronary flow index. The DTI is a valid technique for detecting functional coronary stenosis.
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