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Background : Some patients with chronic obstructive pulmonary disease (COPD) may benefit from oral steroid therapy. These steroid-responsive patients are diagnosed based on laboratory spirometry. We hypothesize that daily, home-based spirometry is a better tool. Methods : Thirty patients with COPD underwent a single-blinded study, with a crossover design. They received 2 weeks of placebo followed by 2 weeks of prednisone therapy (40 mg/day). Laboratory spirometry was done at the beginning and end of the study and daily home-based spirometry was done twice a day. Results : Analysis of variance model was used. The variability of the median day-to-day forced expiratory volume in 1 s (FEV 1 ) was 72.5 mL (25th percentile of 40 mL and 75th percentile of 130 mL). The daily FEV 1 variation was 70 mL (25th percentile of 50 mL and 75th percentile of 100 mL). The overall laboratory FEV 1 variability was larger after the steroid course (P < 0.001), but not clinically significant. The variability was not significant postplacebo treatment compared with the baseline values. For home-based spirometry, steroid treatment was not significantly different. The majority (97%) completed more than 80% of the measurements. Ninety percent of the performed tests were considered acceptable. Only 53% of the tests were considered accurate. Overall both laboratory and home-based measurements did not show significant association between airway responsiveness and dyspnea or exercise capacity. Conclusion : Twice-daily home measurements of FEV 1 might be better than the conventional approach to identify steroid responsive COPD patients. However, this finding was only statistically but not clinically significant. Therefore, we would not recommend this approach to identify COPD patients with steroid responsiveness.

Abstract Background Expression profile of the toll like receptors (TLRs) on PBMCs is central to the regulation of proinflammatory markers. An imbalance in the TLRs expression may lead to several types of inflammatory disorders. Furthermore, the dynamic regulation of inflammatory activity and associated impaired production of cytokines by peripheral blood mononuclear cells (PBMCs) in obese individulas remain poorly understood. Therefore, we determined the perturbation in TLRs (TLR2 and TLR4), their adaptor proteins (MyD88, IRAK1 and TRAF6) expression in PBMCs/subcutaneous adipose tissue (AT) as well as inflammatory cytokines changes in obese individuals. Methods mRNA expression levels of TLR2, TLR4, IL-6, TNF-α and adaptor proteins were determined by RT-PCR. TLR2, TLR4 and adaptor proteins expression in AT was determined by immunohistochemistry. Results Obese and overweight individuals showed significantly increased expression of TLR2, TLR4 and MyD88 in both PBMCs and AT as compared with lean individuals (P Conclusions TLRs and adapter proteins were overexpressed in PBMCs from obese subjects, which correlated with increased expression of TNF-α and IL-6. This association may explain a potential pathophysiological link between obesity and inflammation leading to insulin resistance.

We sought to assess pre-vaccination and post-vaccination seroprevalences of anti-SARS-CoV-2 antibodies in Kuwait and to compare antibody levels between vaccine types. In phase 1 (pre-vaccination period, n = 19,363), blood samples were collected before the launch of COVID-19 vaccination in Kuwait between 1 September and 31 December 2020. Blood samples for phase 2 (post-vaccination period, n = 4973) were collected between 1 September and 30 November 2021. We tested subjects for anti-SARS-CoV-2 antibodies using the DiaSorin LIAISON® SARS-CoV-2 IgM and Trimeric S IgG tests. In the pre-vaccination period, the prevalence of SARS-CoV-2 IgM and IgG was 14.50% (95% CI: 14.01–15.00) and 24.89% (95% CI: 24.29–25.50), respectively. The trend of seropositivity increased with age and was higher for females and non-Kuwaiti participants (p < 0.0001). Interestingly, seroprevalence was significantly higher for those who had received one dose of BNT162b2 (95.21%) than those who had received one dose of ChAdOx1-nCov-19 (92.86%). In addition, those who reported receiving two doses had higher seroprevalence, 96.25%, 95.86%, and 94.93% for ChA-dOx1-nCov-19/AstraZeneca, mix-and-match, and BNT162b2 recipients, respectively. After the second dose, median spike-specific responses showed no significant difference between ChAdOx1-nCov-19 and BNT162b2. Furthermore, statistical analysis showed no significant difference between median anti-trimeric S antibody levels of vaccinated individuals according to sex, age, or nationality (p > 0.05). In contrast, a negative correlation between age and anti-trimeric S IgG titers of BNT162b2-vaccinated subjects was observed (r = −0.062, p = 0.0009). Antibody levels decreased with time after vaccination with both vaccines. Our findings indicate that seroprevalence was very low during the pre-vaccination period (25%) in the general population and was greater than 95% in the vaccinated population in Kuwait. Furthermore, ChAdOx1-nCov-19 and BNT162b2 are effective in generating a similar humoral response. [ABSTRACT FROM AUTHOR]

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COVID-19 is a worldwide pandemic that is mild in most patients but can result in a pneumonia like illness with progression to acute respiratory distress syndrome and death. Predicting the disease severity at time of diagnosis can be helpful in prioritizing hospital admission and resources. We prospectively recruited 1096 consecutive patients of whom 643 met the inclusion criterion with COVID-19 from Jaber Hospital, a COVID-19 facility in Kuwait, between 24 February and 20 April 2020. The primary endpoint of interest was disease severity defined algorithmically. Predefined risk variables were collected at the time of PCR based diagnosis of the infection. Prognostic model development used 5-fold cross-validated regularized logit regression. The model was externally validated against data from Wuhan, China. There were 643 patients with clinical course data of whom 94 developed severe COVID-19. In the final model, age, CRP, procalcitonin, lymphocyte percentage, monocyte percentages and serum albumin were independent predictors of a more severe illness course. The final prognostic model demonstrated good discrimination, and both discrimination and calibration were confirmed with an external dataset. We developed and validated a simple score calculated at time of diagnosis that can predict patients with severe COVID-19 disease reliably and that has been validated externally. The KPI score calculator is now available online at covidkscore.com [ABSTRACT FROM AUTHOR]

Chronic low-grade inflammation and dysregulation of the stress defense system are cardinal features of obesity, a major risk factor for the development of insulin resistance and diabetes. Dual-specificity protein phosphatase 1 (DUSP1), known also as MAP kinase phosphatase 1 (MKP1), is implicated in metabolism and energy expenditure. Mice lacking DUSP1 are resistant to high-fat diet-induced obesity. However, the expression of DUSP1 has not been investigated in human obesity. In the current study, we compared the expression pattern of DUSP1 between lean and obese nondiabetic human subjects using subcutaneous adipose tissue (SAT) and peripheral blood mononuclear cells (PBMCs). The levels of DUSP1 mRNA and protein were significantly increased in obese subjects with concomitant decrease in the phosphorylation of p38 MAPK (p-p38 MAPK) and PGC-1α and an increase in the levels of phospho-JNK (p-JNK) and phospho-ERK (p-ERK). Moreover, obese subjects had higher levels of circulating DUSP1 protein that correlated positively with various obesity indicators, triglycerides, glucagon, insulin, leptin, and PAI-1 (P < 0.05) but negatively with Vo2max and high-density lipoprotein (P < 0.05). The observation that DUSP1 was overexpressed in obese subjects prompted us to investigate whether physical exercise could reduce its expression. In this study, we report for the first time that physical exercise significantly attenuated the expression of DUSP1 in both the SAT and PBMCs, with a parallel increase in the expression of PGC-1α and a reduction in the levels of p-JNK and p-ERK along with attenuated inflammatory response. Collectively, our data suggest that DUSP1 upregulation is strongly linked to adiposity and that physical exercise modulates its expression. This gives further evidence that exercise might be useful as a strategy for managing obesity and preventing its associated complications [ABSTRACT FROM AUTHOR]

Background Obesity is characterized by a chronic low-grade inflammation and altered stress responses in key metabolic tissues. Impairment of heat shock response (HSR) has been already linked to diabetes and insulin resistance as reflected by decrease in heat shock proteins (HSPs) expression. However, the status of HSR in non-diabetic human obese has not yet been elucidated. The aim of the current study was to investigate whether obesity triggers a change in the HSR pattern and the impact of physical exercise on this pattern at protein and mRNA levels. Methods Two groups of adult non-diabetic human subjects consisting of lean and obese (n = 47 for each group) were enrolled in this study. The expression pattern of HSP-27, DNAJB3/HSP- 40, HSP-60, HSC-70, HSP72, HSP-90 and GRP-94 in the adipose tissue was primarily investigated by immunohistochemistry and then complemented by western blot and qRTPCR in Peripheral blood mononuclear cells (PBMCs). HSPs expression levels were correlated with various physical, clinical and biochemical parameters. We have also explored the effect of a 3-month moderate physical exercise on the HSPs expression pattern in obese subjects. Results Obese subjects displayed increased expression of HSP-60, HSC-70, HSP-72, HSP-90 and GRP-94 and lower expression of DNAJB3/HSP-40 (P < 0.05). No differential expression was observed for HSP-27 between the two groups. Higher levels of HSP-72 and GRP-94 proteins correlated positively with the indices of obesity (body mass index and percent body fat) and circulating levels of IFN-gamma-inducible protein 10 (IP-10) and RANTES chemokines. This expression pattern was concomitant with increased inflammatory response in the adipose tissue as monitored by increased levels of Interleukin-6 (IL-6), Tumor necrosis factor-α (TNF-α), and RANTES (P < 0.05). Physical exercise reduced the expression of various HSPs in obese to normal levels observed in lean subjects with a parallel decrease in the endogenous levels of IL-6, TNF-α, and RANTES. Conclusion Taken together, these data indicate that obesity triggers differential regulation of various components of the HSR in non-diabetic subjects and a 3-month physical moderate exercise was sufficient to restore the normal expression of HSPs in the adipose tissue with concomitant attenuation in the inflammatory response. [ABSTRACT FROM AUTHOR]

Objective Recent studies have demonstrated a protective role for IL-33 against obesity-associated inflammation, atherosclerosis and metabolic abnormalities. IL-33 promotes the production of T helper type 2 (Th2) cytokines, polarizes macrophages towards a protective alternatively activated phenotype, reduces lipid storage and decreases the expression of genes associated with lipid metabolism and adipogenesis. Our objective was to determine the level of serum IL-33 in non-diabetic and diabetic subjects, and to correlate these levels with clinical (BMI and body weight) and metabolic (serum lipids and HbA1c) parameters. Methods The level of IL-33 was measured in the serum of lean, overweight and obese non-diabetic and diabetic subjects, and then correlated with clinical and metabolic parameters. Results Non-lean subjects had significantly (P = 0.01) lower levels of IL-33 compared to lean controls. IL-33 was negatively correlated with the BMI and body weight in lean and overweight, but not obese (non-diabetic and diabetic), subjects. IL-33 is associated with protective lipid profiles, and is negatively correlated with HbA1c, in non-diabetic (lean, overweight and obese) but not diabetic subjects. Conclusions Our data support previous findings showing a protective role for IL-33 against adiposity and atherosclerosis, and further suggest that reduced levels of IL-33 may put certain individuals at increased risk of developing atherosclerosis and insulin resistance. Therefore, IL-33 may serve as a novel marker to predict those who may be at increased risk of developing atherosclerosis. [ABSTRACT FROM AUTHOR]

RANTES and its CCR5 receptor trigger inflammation and its progression to insulin resistance in obese. In the present study, we investigated for the first time the effect of physical exercise on the expression of RANTES and CCR5 in obese humans. Fiftyseven adult nondiabetic subjects (17 lean and 40 obese) were enrolled in a 3-month supervised physical exercise. RANTES and CCR5 expressions were measured in PBMCs and subcutaneous adipose tissue before and after exercise. Circulating plasma levels of RANTES were also investigated.There was a significant increase in RANTES and CCR5 expression in the subcutaneous adipose tissue of obese compared to lean. In PBMCs, however, while the levels of RANTES mRNA and protein were comparable between both groups, CCR5 mRNA was downregulated in obese subjects (ρ < 0.05). Physical exercise significantly reduced the expression of both RANTES and CCR5 (ρ < 0.05) in the adipose tissue of obese individuals with a concomitant decrease in the levels of the inflammatory markers TNFα, IL-6, and P-JNK. Circulating RANTES correlated negatively with anti-inflammatory IL-1ra (ρ = 0.001) and positively with proinflammatory IP-10 and TBARS levels (ρ < 0.05).Therefore, physical exercise may provide an effective approach for combating the deleterious effects associated with obesity through RANTES signaling in the adipose tissue [ABSTRACT FROM AUTHOR]

Obesity is a major risk factor for a myriad of disorders such as insulin resistance and diabetes. The mechanisms underlying these chronic conditions are complex but low grade inflammation and alteration of the endogenous stress defense system are well established. Previous studies indicated that impairment of HSP-25 and HSP-72 was linked to obesity, insulin resistance and diabetes in humans and animals while their induction was associated with improved clinical outcomes. In an attempt to identify additional components of the heat shock response that may be dysregulated by obesity, we used the RT2-Profiler PCR heat shock array, complemented with RT-PCR and validated by Western blot and immunohistochemistry. Using adipose tissue biopsies and PBMC of non-diabetic lean and obese subjects, we report the downregulation of DNAJB3 cochaperone mRNA and protein in obese that negatively correlated with percent body fat (P = 0.0001), triglycerides (P = 0.035) and the inflammatory chemokines IP-10 and RANTES (P = 0.036 and P = 0.02, respectively). DNAJB positively correlated with maximum oxygen consumption (P = 0.031). Based on the beneficial effect of physical exercise, we investigated its possible impact on DNAJB3 expression and indeed, we found that exercise restored the expression of DNAJB3 in obese subjects with a concomitant decrease of phosphorylated JNK. Using cell lines, DNAJB3 protein was reduced following treatment with palmitate and tunicamycin which is suggestive of the link between the expression of DNAJB3 and the activation of the endoplasmic reticulum stress. DNAJB3 was also shown to coimmunoprecipiate with JNK and IKKβ stress kinases along with HSP-72 and thus, suggesting its potential role in modulating their activities. Taken together, these data suggest that DNAJB3 can potentially play a protective role against obesity. [ABSTRACT FROM AUTHOR]

Background/Objective: Osteopontin (OPN) and IL-18 are known inflammatory mediators and both participate in a wide range of biological processes linked to immunological disorders. Since an interaction between OPN and IL-18 has not been studied in obesity, we investigated whether: (i) their levels were simultaneously elevated in obese individuals; (ii) OPN was associated with IL-18 in obese individuals and (iii) their levels associated with fasting blood glucose (FBG) and BMI. Subjects and Methods: PBMCs and plasma samples were isolated from 60 individuals including lean as well as overweight and obese individuals. Subcutaneous adipose tissue samples were obtained. OPN and IL-18 were measured by ELISA. OPN and IL-18 mRNA expression was quantified by real time quantitative RT-PCR. Results: Obese individuals exhibited significantly increased circulating OPN levels as compared with lean individuals (obese 2865±101; lean 1681±116 pg/ml; P<0.0001). IL-18 levels were also high in obese individuals (obese 491±39, lean 301±26 pg/ml; P = 0.0009). OPN and IL-18 expression were simultaneously up-regulated (OPN: 5.4-Fold; IL-18: 8.9-Fold; P<0.05) in PBMCs from obese individuals compared to lean group. Adipose tissue from obese individuals had high expression of OPN (7.3-Fold) and IL-18 (9.6-Fold). Plasma OPN levels correlated positively with FBG levels (r = 0.32, P = 0.02). Similarly, IL-18 correlated positively with FBG levels (r = 0.406, P = 0.0042). Stepwise multiple regression analysis showed an independent association of BMI with OPN and IL-18. Interestingly, OPN levels increased progressively with an increase in IL-18 levels (r = 0.52, P = 0.0004). We also examined the regulatory role of IL-18 in OPN secretion from PBMCs. Neutralizing anti-IL-18Rα mAb reduced OPN secretion. Conclusion: These findings represent the first observation that plasma, PBMC and adipose tissue OPN and IL-18 are simultaneously increased and correlate with each other in overweight/obese individuals which may trigger the development of obesity-associated insulin resistance. Moreover, these results provide the direct evidence that IL-18 regulates OPN production in PBMCs. [ABSTRACT FROM AUTHOR]

An abstract of the article "Association of obesity with down-regulation of heat shock protein 40 expression and evidence that exercise retrieves its normal expression," by Jehad Abubakr, Mohamed Abu-Farha, and Monira Al-Arouj is presented.

Sedentary lifestyle and excessive energy intake are prominent contributors to obesity; a major risk factors for the development of insulin resistance, type 2 diabetes and cardiovascular diseases. Elucidating the molecular mechanisms underlying these chronic conditions is of relevant importance as it might lead to the identification of novel anti-obesity targets. The purpose of the current study is to investigate differentially expressed proteins between lean and obese subjects through a shot-gun quantitative proteomics approach using peripheral blood mononuclear cells (PBMCs) extracts as well as potential modulation of those proteins by physical exercise. Using this approach, a total of 47 proteins showed at least 1.5 fold change between lean and obese subjects. In obese, the proteomic profiling before and after 3 months of physical exercise showed differential expression of 38 proteins. Thrombospondin 1 (TSP1) was among the proteins that were upregulated in obese subjects and then decreased by physical exercise. Conversely, the histone deacetylase 4 (HDAC4) was downregulated in obese subjects and then induced by physical exercise. The proteomic data was further validated by qRT-PCR, Western blot and immunohistochemistry in both PBMCs and adipose tissue. We also showed that HDAC4 levels correlated positively with maximum oxygen consumption (VO2 Max) but negatively with body mass index, percent body fat, and the inflammatory chemokine RANTES. In functional assays, our data indicated that ectopic expression of HDAC4 significantly impaired TNF-α-dependent activation of NF-κB, establishing thus a link between HDAC4 and regulation of the immune system. Together, the expression pattern of HDAC4 in obese subjects before and after physical exercise, its correlation with various physical, clinical and metabolic parameters along with its inhibitory effect on NF-κB are suggestive of a protective role of HDAC4 against obesity. HDAC4 could therefore represent a potential therapeutic target for the control and management of obesity and presumably insulin resistance. [ABSTRACT FROM AUTHOR]

The first case of cavitary pulmonary disease caused by Purpureocillium lilacinum is described. The isolate showed atypical microscopic characteristics similar to Acremonium and Fusarium spp., which necessitated molecular identification by sequencing of multiple conserved loci. The patient responded to voriconazole, reinforcing its therapeutic efficacy for P. lilacinum infections.

Background: The frequency of metabolic alkalosis among adults with stable severe CF-lung disease is unknown., Methods: Retrospective chart review., Results: Fourteen CF and 6 COPD (controls) patients were included. FEV1 was similar between the two groups. PaO2 was significantly higher in the COPD (mean ± 2 SD is 72.0 ± 6.8 mmHg,) than in the CF group (56.1 ± 4.1 mmHg). The frequency of metabolic alkalosis in CF patients (12/14, 86%) was significantly greater (p=0.04) than in the COPD group (2/6, 33%). Mixed respiratory acidosis and metabolic alkalosis was evident in 4 CF and 1 COPD patients. Primary metabolic alkalosis was observed in 8 CF and none of the COPD patients. One COPD patient had respiratory and metabolic alkalosis., Conclusions: Metabolic alkalosis is more frequent in stable patients with CF lung disease than in COPD patients. This might be due to defective CFTR function with abnormal electrolyte transport within the kidney and/ or gastrointestinal tract.

An unusual case of pleuroparenchymal lung disease caused by the inhalation of vermiculite dust, presumably containing asbestos fibers is described. The uniqueness of the case lies in the very indirect nature of exposure -- the wife of a factory owner, rather than a worker exposed to asbestos, whose factory manufactured vermiculite. The present case illustrates the importance of taking careful occupational histories of all household members when presented with a patient whose chest radiograph exhibits features consistent with asbestos exposure.