Autoimmune Progressive Fibrosing Interstitial Lung Disease: Predictors of Fast Decline

A subset of interstitial lung diseases (ILDs) with autoimmune traits—including connective tissue disease-associated ILD (CTD-ILD) and interstitial pneumonia with autoimmune features (IPAF)—develops progressive fibrosing (PF)-ILD. The aim of our study was to evaluate the clinical characteristics and predictors of longitudinal lung function (LF) changes in autoimmune PF-ILD patients in a real-world setting. All ILD cases with confirmed or suspected autoimmunity discussed by a multidisciplinary team (MDT) between January 2017 and June 2019 (n = 511) were reviewed, including 63 CTD-ILD and 44 IPAF patients. Detailed medical history, LF test, diffusing capacity of the lung for carbon monoxide (DLCO), 6-min walk test (6MWT), blood gas analysis (BGA), and high-resolution computer tomography (HRCT) were performed. Longitudinal follow-up for functional parameters was at least 2 years. Women were overrepresented (70.1%), and the age of the IPAF group was significantly higher as compared to the CTD-ILD group (p < 0.001). Dyspnea, crackles, and weight loss were significantly more common in the IPAF group as compared to the CTD-ILD group (84.1% vs. 58.7%, p = 0.006; 72.7% vs. 49.2%, p = 0.017; 29.6% vs. 4.8%, p = 0.001). Forced vital capacity (FVC) yearly decline was more pronounced in IPAF (53.1 ± 0.3 vs. 16.7 ± 0.2 ml; p = 0.294), while the majority of patients (IPAF: 68% and CTD-ILD 82%) did not deteriorate. Factors influencing progression included malignancy as a comorbidity, anti-SS-A antibodies, and post-exercise pulse increase at 6MWT. Antifibrotic therapy was administered significantly more often in IPAF as compared to CTD-ILD patients (n = 13, 29.5% vs. n = 5, 7.9%; p = 0.007), and importantly, this treatment reduced lung function decline when compared to non-treated patients. Majority of patients improved or were stable regarding lung function, and autoimmune-associated PF-ILD was more common in patients having IPAF. Functional decline predictors were anti-SS-A antibodies and marked post-exercise pulse increase at 6MWT. Antifibrotic treatments reduced progression in progressive fibrosing CTD-ILD and IPAF, emphasizing the need for guidelines including optimal treatment start and combination therapies in this special patient group.

Trajectories of Body Mass Index and Multimorbidity in Old Age: 12-Year Results From a Population-Based Study

We aimed to study the association of long-terms trajectories of body mass index (BMI) with contemporaneous changes in multimorbidity development in older adults. Twelve-year BMI trajectories (2001–2013) were identified in subjects aged 60+ years from the Swedish National Study on Aging and Care-Kungsholmen (SNAC-K) using growth mixture models (N=2,189). Information on chronic diseases and multimorbidity was ascertained based on clinical examinations, lab tests, medications, and inpatient and outpatient medical records. Linear mixed models were used to study the association between BMI trajectories and the speed of chronic diseases accumulation, in general and by groups of cardiovascular and neuropsychiatric diseases. Eighty percent of the study population was included in a stable BMI trajectory, 18% in a slow-decline trajectory with an accelerated BMI decline from age 78 onwards, and 2% in a fast-decline trajectory that reached underweight values before age 85. A significantly higher yearly rate of chronic disease accumulation was observed in the fast-decline versus stable trajectories (β=0.221, 95% CI 0.090-0.352) after adjusting for age, sex, education and time to death. Subjects in the slow-decline trajectory showed a significantly higher rate of cardiovascular diseases accumulation (β=0.016, 95% CI 0.000-0.031); those in the fast-decline trajectory showed a faster accumulation of both cardiovascular (β=0.020, 95% CI -0.025, 0.064) and neuropsychiatric diseases (β=0.102, 95% CI 0.064-0.139), even if the former association did not reach statistical significance. Carefully monitoring older adults with sustained weight loss seems relevant given their likelihood to develop a phenotype of rapidly accumulating chronic -especially neuropsychiatric- diseases.

Hydro-meteorological Correlations of Himalayan Glaciers: A Review

This review manuscript addresses hydro-meteorological correlations of various glaciers situated in the Himalayan region. Meteorological parameters influence the discharge pattern of the glacier. A strong correlation has been observed between discharge and air temperature of the studied Himalayan glaciers. Whereas, other meteorological parameters such as wind speed and wind direction etc. were not significantly correlated with the meltwater runoff of different glaciers in this region. In general, variability (Cv) in discharge from the various Himalayan glaciers such as Chhota Shigri and Gangotri glaciers follow the variability (Cv) in the temperature of these glaciers. Maximum variability (Cv) in meltwater runoff from the Chhota Shigri glacier has been reported in the month of September, which might be due to the fast decline in stream runoff and air temperature of the study area during the month of September. A strong relationship has been observed between suspended sediment concentration and temperature of the majority of studied Himalayan glaciers. Such type of result shows that the suspended sediment concentration in the glacial meltwater has increased with rising air temperature in this region.

Quantitative Determination of the Effects of He-Ne Laser Irradiation on Seed Thermodynamics, Germination Attributes and Metabolites of Safflower (Carthamus tinctorius L.) in Relation with the Activities of Germination Enzymes

The present investigation was undertaken to assess the effects of different doses (100, 300, and 500 mJ) of low power He–Ne laser (632.8 nm) irradiation on seed germination and thermodynamics attributes and activities of potential germinating enzymes in relation with changes in seed metabolites. He–Ne laser seed irradiation increased the amylase (Amy), protease (Pro) and glucosidase (Gluco) activities, with a significant improvement in seed thermodynamics and seed germination attributes. A fast increase was found in free fatty acids (FFA), free amino acids (FAA), chlorophyll (Chl), carotenoids (Car), total soluble sugars (TSS) and reducing sugars (RS) in laser treated seeds in parallel with fast decline in seed oil contents and total soluble proteins (TSP). Significant positive correlations were recorded in laser-induced enhanced seed energy levels, germination, activities of germination enzymes with levels of FAA, FFA, Chl, TSS and RS, but a negative correlation with the levels of TSP and oil. In conclusion, the seed treatment with 100 and 300 mJ He–Ne laser was more effective to improve the seed germination potential associated with an improvement in seed energy levels due to increased activities of germination enzymes due to the speedy breakdown of seed reserves to simple metabolites as building blocks.

Serum metabolomics study of the association between dairy intake and the anti-müllerian hormone annual decline rate

Background Dairy intake has been implicated in later ovarian aging but mechanism underlying the association is unknown. This study aimed to investigate (1) associations between dairy intake and metabolites previously shown related to anti-müllerian hormone (AMH) decline rate; (2) mediating roles of these metabolites in the prospective association of total dairy consumption with odds of AMH fast decline rate. Methods The participants comprised 186 reproductive-aged women randomly selected from the Tehran Lipid and Glucose Study. AMH was measured at baseline (1999–2001) and the 5th follow-up (2014–2017), and dietary data was collected at the second follow-up (2005–2008) using a food frequency questionnaire. Untargeted metabolomics was performed by gas chromatography–mass spectrometry using fasting-serum samples of the second follow-up. We analyzed dairy intake in association with the eight metabolites linked to the higher odds of AMH fast decline rate using linear regression with the Benjamini–Hochberg false discovery correction. Mediatory roles of the metabolites were assessed by bootstrapping. Results Mean age and BMI of the participants at metabolomics assessment were 44.7 ± 5.87 years and 28.8 ± 4.88 kg/m2, respectively. Phosphate, branched-chain amino acids (BCAAs), and proline decreased significantly from the first to the third tertile of total dairy intake. Total dairy as a continuous variable inversely associated with phosphate (beta = −0.166; p value = 0.018), valine (beta = −0.176; p value = 0.016), leucine (beta = −0.226; p value = 0.002), proline (beta = −0.219; p value = 0.003), and urea (beta = −0.156; p = 0.035) after accounting for all potential covariates and correction for multiplicity (q-value < 0.1). Fermented dairy showed similar results, but milk did not associate with any of the metabolites. Simple mediation showed significant indirect effects for phosphate, proline, and BCAAs but not urea. Entering the sum of phosphate, proline, and BCAAs as a mediator, the metabolites' total indirect effects were significant [β = −0.12 (95% CIs − 0.26, − 0.04)]. In contrast, the direct association of total dairy intake with the fast decline in AMH was non-significant [β = −0.28 (95% CIs − 0.67, 0.10)]. Conclusions Total dairy was inversely associated with AMH decline rate-related metabolites. Inverse association of dairy intakes with the odds of AMH fast decline rate was indirectly mediated by lower phosphate, proline, and BCAAs.

DIVERSITY OF PTERIDOPHYTES IN WESTERN GHATS- A REVIEW

Pteridophytes are vascular cryptogams that dominated the earth 250 million years ago. Currently, there are 13,600 species of pteridophytes around the world, and is the second most dominant plant group. In India, there are 1200 pteridophyte species with 70 families and 192 genera. The pteridophyte hotspots in India are the Himalayas, Western Ghats, Eastern Ghats, Central India, and Andaman and the Nicobar Islands. The Western Ghats occupies only 6% of the Indian landmass and still holds a pteridophyte diversity of 383 species. Fern and fern allies are highly sensitive to changes in their natural habitat, thus habitat destruction, anthropogenic influences, climate change, etc., are causing a fast decline in their population. Epiphytic species are easily destroyed due to the felling of trees and because of this at present 41- 43% of epiphytic pteridophytes in India are reported to be threatened. It necessitates the frequent analysis of the pteridophyte flora of a region to ensure the existence of its species diversity. The potential of in-vitro and ex-situ conservation techniques can be explored for the conservation of threatened pteridophyte species

The role of APOE in cognitive trajectories and motor decline in Parkinson’s disease

We aimed to investigate the role of the APOE genotype in cognitive and motor trajectories in Parkinson’s disease (PD). Using PD registry data, we retrospectively investigated a total of 253 patients with PD who underwent the Mini-Mental State Exam (MMSE) two or more times at least 5 years apart, were aged over 40 years, and free of dementia at the time of enrollment. We performed group-based trajectory modeling to identify patterns of cognitive change using the MMSE. Kaplan–Meier survival analysis was used to investigate the role of the APOE genotype in cognitive and motor progression. Trajectory analysis divided patients into four groups: early fast decline, fast decline, gradual decline, and stable groups with annual MMSE scores decline of − 2.8, − 1.8, − 0.6, and − 0.1 points per year, respectively. The frequency of APOE ε4 was higher in patients in the early fast decline and fast decline groups (50.0%) than those in the stable group (20.1%) (p = 0.007). APOE ε4, in addition to older age at onset, depressive mood, and higher H&Y stage, was associated with the cognitive decline rate, but no APOE genotype was associated with motor progression. APOE genotype could be used to predict the cognitive trajectory in PD.

Physiology and behavior under food limitation support an escape, not preparative, response in the nomadic Pine Siskin (Spinus pinus)

Migration allows animals to use resources that are variable in time and/or space, with different migratory strategies depending on the predictability of resource variation. When food varies seasonally, obligate migrants anticipate and prepare for migration. In contrast, facultative migrants, whose movements are unpredictable in timing and destination, may either prepare for migration or escape when resources are depleted. We propose and test two alternative hypotheses regarding the behavioral and physiological responses of facultative migrants to declining food availability. (1) The Prepare Hypothesis predicts that facultative migrants prepare for departure by increasing fuel stores in response to declining food availability, and elevations of baseline corticosterone (CORT) facilitate increased activity. (2) The Escape Hypothesis predicts that facultative migrants do not prepare for departure, body condition declines as food availability declines, and stress-induced levels of CORT induce escape behavior when both energetic condition and food resources are low. We conducted a 16-day experiment, measuring body composition (using Quantitative Magnetic Resonance), activity (using force perches), and baseline CORT in Pine Siskins (Spinus pinus) given ad libitum food or a slow decline, fast decline, or randomly changing amount of food. Our results support the Escape Hypothesis: body condition declined as food declined, decreases in body and fat mass were associated with increases in baseline CORT, and activity increased only when food availability was low. This work suggests that facultative migration in autumn allows birds to escape low resource areas and that the underlying physiological mechanisms differ from those driving both seasonal, obligate migrations and spring nomadic movements.

Serum metabolomics study of women with different annual decline rates of anti-Müllerian hormone: an untargeted gas chromatography–mass spectrometry-based study

STUDY QUESTION Which metabolites are associated with varying rates of ovarian aging, measured as annual decline rates of anti-Müllerian hormone (AMH) concentrations? SUMMARY ANSWER Higher serum concentrations of metabolites of phosphate, N-acetyl-d-glucosamine, branched chained amino acids (BCAAs), proline, urea and pyroglutamic acid were associated with higher odds of fast annual decline rate of AMH. WHAT IS KNOWN ALREADY Age-related rate of ovarian follicular loss varies among women, and the factors underlying such inter-individual variations are mainly unknown. The rate of ovarian aging is clinically important due to its effects on both reproduction and health of women. Metabolomics, a global investigation of metabolites in biological samples, provides an opportunity to study metabolites or metabolic pathways in relation to a physiological/pathophysiological condition. To date, no metabolomics study has been conducted regarding the differences in the rates of ovarian follicular loss. STUDY DESIGN, SIZE, DURATION This prospective study was conducted on 186 reproductive-aged women with regular menstrual cycles and history of natural fertility, randomly selected using random case selection option in SPSS from the Tehran Lipid and Glucose Study. PARTICIPANTS/MATERIALS, SETTING, METHODS AMH concentrations were measured at baseline (1999–2001) and the fifth follow-up examination (2014–2017), after a median follow-up of 16 years, by immunoassay using Gen II kit. The annual decline rate of AMH was calculated by dividing the AMH decline rate by the follow-up duration (percent/year). The women were categorized based on the tertiles of the annual decline rates. Untargeted metabolomics analysis of the fasting-serum samples collected during the second follow-up examination cycle (2005–2008) was performed using gas chromatography–mass spectrometry. A combination of univariate and multivariate approaches was used to investigate the associations between metabolites and the annual decline rates of AMH. MAIN RESULTS AND THE ROLE OF CHANCE After adjusting the baseline values of age, AMH and BMI, 29 metabolites were positively correlated with the annual AMH decline rates. The comparisons among the tertiles of the annual decline rate of AMH revealed an increase in the relative abundance of 15 metabolites in the women with a fast decline (tertile 3), compared to those with a slow decline (tertile 1). There was no distinct separation between women with slow and fast decline rates while considering 41 metabolites simultaneously using the principal component analysis and the partial least-squares discriminant analysis models. The odds of fast AMH decline was increased with higher serum metabolites of phosphate, N-acetyl-d-glucosamine, BCAAs, proline, urea and pyroglutamic acid. Amino sugar and nucleotide sugar metabolism, BCAAs metabolism and aminoacyl tRNA biosynthesis were among the most significant pathways associated with the fast decline rate of AMH. LIMITATIONS, REASONS FOR CAUTION Estimating the annual decline rates of AMH using the only two measures of AMH is the main limitation of the study which assumes a linear fixed reduction in AMH during the study. Since using the two-time points did not account for the variability in the decline rate of AMH, the annual decline rates estimated in this study may not accurately show the trend of the reduction in AMH. In addition, despite the longitudinal nature of the study and statistical adjustment of the participants’ ages, it is difficult to distinguish the AMH-related metabolites observed in this study can accelerate ovarian aging or they are reflections of different rates of the aging process. WIDER IMPLICATIONS OF THE FINDINGS Some metabolite features related to the decline rates of AMH have been suggested in this study; further prospective studies with multiple measurements of AMH are needed to confirm the findings of this study and to better understand the molecular process underlying variations in ovarian aging. STUDY FUNDING/COMPETING INTEREST(S) This study, as a part of PhD thesis of Ms Nazanin Moslehi, was supported by Shahid Beheshti University of Medical Sciences (10522-4). There were no competing interests. TRIAL REGISTRATION NUMBER N/A