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1.
Article in English | MEDLINE | ID: mdl-39320093

ABSTRACT

COVID-19 commonly presents as pneumonia, with those most severely affected progressing to respiratory failure. Patient responses to SARS-CoV-2 infection are varied, with comorbidities acting as contributors to varied outcomes. Focusing on one such major comorbidity, we assessed whether pharmacological induction of Type I Diabetes Mellitus (T1DM) would increase the severity of lung injury in a murine model of COVID-19 pneumonia utilizing wild type mice infected with mouse-adapted SARS-CoV-2. Hyperglycemic mice exhibited increased weight loss and reduced blood oxygen saturation in comparison to their euglycemic counterparts, suggesting that these animals indeed experienced more severe lung injury. Transcriptomic analysis revealed a significant impairment of the adaptive immune response in the lungs of diabetic mice compared to those of control. In order to expand the options available for tissue analysis due to biosafety restrictions, we employed a new technique to digest highly fixed tissue into a single cell suspension, originally designed for scRNA-Seq, which we then adapted for flow cytometric analysis. Flow immunophenotyping and scRNA-Seq confirmed impaired recruitment of T cells into the lungs of T1DM animals. Additionally, scRNA-Seq revealed a distinct, highly inflammatory macrophage profile in the diabetic cohort that correlates with the more severe infection these mice experienced clinically, allowing insight into a possible mechanism for this phenomenon. Recognizing the near certainty that respiratory viruses will continue to present significant public health concerns for the foreseeable future, our study provides key insights into how T1DM results in a much more severe infection and identifies possible targets to ameliorate comorbidity-associated severe disease.

2.
Br J Anaesth ; 2024 Oct 09.
Article in English | MEDLINE | ID: mdl-39389833

ABSTRACT

BACKGROUND: Nitrous oxide (N2O) is a potent greenhouse gas that contributes significantly to the healthcare sector's carbon footprint. Pre-utilisation losses of N2O are up to 95%. Decommissioning manifolds can reduce these losses. METHODS: Hospitals in our Greater London research network with at least one active N2O manifold were included in the Nitrous Oxide Manifold and Other Reduction of Emissions (NoMoreGas) study. N2O utilisation data were collected continuously over 5 days and extrapolated over a year, in addition to collecting procurement records from the preceding financial year. The primary outcome was the discrepancy between clinically utilised N2O and the quantity procured by hospitals, referred to as the 'N2O gap'. Secondary outcomes included anaesthetists' self-reported utilisation of N2O and their opinions on manifold decommissioning. RESULTS: Eighteen of 53 hospitals were included. In total, 6 487 200 L of N2O were procured with a median (IQR) of 304 200 (183 600-473 400) L per site. During the 5-day data collection period, sites utilised a median (IQR) of 501 (42-1409) L of N2O. Extrapolating over a year resulted in a median (IQR) annual utilisation of 36 573 (3066-102 857) L per site and a total of 1 175 348 L. This represented an estimated 18% of the N2O procured, suggesting pre-utilisation losses of 5 311 852 L. Among surveyed anaesthetists, 70% (n=309) reported using N2O within the previous year, with one-third (n=97) using it once a week or more. There was widespread support for decommissioning manifolds. CONCLUSIONS: Consistent with other reports, the data demonstrate a substantial discrepancy between the quantities of N2O procured and utilised clinically, indicative of significant pre-utilisation losses. Our findings support the decommissioning of N2O manifolds for environmental and economic benefits.

3.
Oecologia ; 190(2): 297-308, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30707296

ABSTRACT

The individual behavioral traits of predators and prey sometimes determine the outcome of their interactions. Here, we examine whether changes to habitat complexity alter the effects of predator and prey behavior on their survival rates. Specifically, we test whether behavioral traits (activity level, boldness, and perch height) measured in predators and prey or multivariate behavioral volumes best predict the survival rates of both trophic levels in staged mesocosms with contrasting structural complexity. Behavioral volumes and hypervolumes are a composite group-level behavioral diversity metric built from the individual-level behavioral traits we measured in predators and prey. We stocked mesocosms with a host plant and groups of cannibalistic predators (n = 5 mantises/mesocosm) and their prey (n = 15 katydids/mesocosm), and mesocosms varied in the presence/absence of additional non-living climbing structures. We found that mantis survival rates were unrelated to any behavioral metric considered here, but were higher in structurally complex mesocosms. Unexpectedly, katydids were more likely to survive when mantis groups occupied larger behavioral volumes, indicating that more behaviorally diverse predator groups are less lethal. Katydid mortality was also increased when both predators and prey exhibited higher average perch heights, but this effect was increased by the addition of supplemental structure. This is consistent with the expectation that structural complexity increases the effect of intraspecific behavioral variation on prey survival rates. Collectively, these results convey that the effects of predator and prey behavior on prey survival could depend highly on the environment in which they are evaluated.


Subject(s)
Perches , Predatory Behavior , Animals , Cannibalism , Ecosystem , Survival Rate
4.
Adv Funct Mater ; 27(39)2017 Oct 19.
Article in English | MEDLINE | ID: mdl-30853878

ABSTRACT

Unlocking the secrets of the brain is a task fraught with complexity and challenge - not least due to the intricacy of the circuits involved. With advancements in the scale and precision of scientific technologies, we are increasingly equipped to explore how these components interact to produce a vast range of outputs that constitute function and disease. Here, an insight is offered into key areas in which the marriage of neuroscience and nanotechnology has revolutionized the industry. The evolution of ever more sophisticated nanomaterials culminates in network-operant functionalized agents. In turn, these materials contribute to novel diagnostic and therapeutic strategies, including drug delivery, neuroprotection, neural regeneration, neuroimaging and neurosurgery. Further, the entrance of nanotechnology into future research arenas including optogenetics, molecular/ion sensing and monitoring, and piezoelectric effects is discussed. Finally, considerations in nanoneurotoxicity, the main barrier to clinical translation, are reviewed, and direction for future perspectives is provided.

5.
J Clin Rheumatol ; 23(5): 273-277, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28700529

ABSTRACT

BACKGROUND: Among patients with rheumatoid arthritis (RA), smoking increases risk of severe RA and pulmonary and cardiovascular disease. Despite this, little is known about smoking cessation counseling by rheumatologists. OBJECTIVES: We examined predictors of tobacco counseling in RA patients who smoke including the effect of perceived RA control. We hypothesized that patients with controlled RA would receive more counseling according to the competing demands model, which explains that preventive care gaps occur as a result of competing provider, patient, and clinic factors. METHODS: This secondary data analysis involved RA patients with an additional cardiovascular disease risk factor identified in an academic medical center 2004-2011. Trained abstractors assessed documented smoking counseling and rheumatologists' impression of RA control in clinic notes. We used multivariable logistic regression to predict having received smoking cessation counseling, including sociodemographics and comorbidity in models. RESULTS: We abstracted 3396 RA visits, including 360 visits (10%) with active smokers. Perceived controlled RA was present in 31% of visits involving smokers (39% in nonsmokers). Beyond nurse documentation, providers documented smoking status in 39% of visit notes with smokers and smoking cessation counseling in 10%. Visits with controlled versus active RA were less likely to include counseling (odds ratio, 0.3; confidence interval, 0.1-0.97). Counseling was more likely in visits with prevalent cardiovascular, pulmonary, and psychiatric disease, but decreased with obesity. CONCLUSIONS: Smoking cessation counseling was documented in 10% of visits and was less likely when RA was controlled. Given smoking's impact on RA and long-term outcomes, systematic cessation counseling efforts are needed.


Subject(s)
Arthritis, Rheumatoid , Cardiovascular Diseases , Directive Counseling/methods , Lung Diseases , Smoking Cessation , Smoking , Adult , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/psychology , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Female , Humans , Lung Diseases/epidemiology , Lung Diseases/etiology , Male , Middle Aged , Needs Assessment , Preventive Medicine/methods , Quality Improvement , Rheumatologists/standards , Risk Factors , Smoking/adverse effects , Smoking/epidemiology , Smoking Cessation/methods , Smoking Cessation/psychology , United States/epidemiology
6.
Rheumatology (Oxford) ; 54(8): 1415-9, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25731768

ABSTRACT

OBJECTIVE: RA increases vascular disease and angiogenesis, yet a 1964 Lancet report paradoxically linked RA to lower diabetic retinopathy. Our objective was to examine RA as a risk factor for diabetic retinopathy compared with other vascular risk factors. METHODS: This cohort study compared the prevalence of diabetic retinopathy in diabetes patients with and without RA in a 5% Medicare sample. We analysed the impact of RA on the prevalence of diabetic retinopathy using multivariate logistic regression calculating adjusted rate ratios (ARRs) controlling for sociodemographics, co-morbidity and health utilization. Sensitivity analysis examined eye exam rates. RESULTS: Among 256 331 Medicare diabetes patients, 5572 (2%) had RA. Diabetic retinopathy was less prevalent in patients with RA compared with those without RA (13.7% vs 16.1%, P ≤ 0.01). Compared with patients without RA, the adjusted model demonstrated that patients with diabetes and RA were 28% less likely to have diabetic retinopathy and 4% more likely to receive an eye exam [ARR 0.72 (95% CI 0.67, 0.77), ARR 1.04 (95% CI 1.02, 1.06)]. CONCLUSION: Findings support the 1964 paradox observing decreased diabetic retinopathy in patients with RA. These findings pose new questions regarding whether RA physiology or treatments protect against diabetic retinopathy and how intraocular factors vary in contrast to adverse vascular changes elsewhere.


Subject(s)
Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/physiopathology , Diabetic Retinopathy/epidemiology , Diabetic Retinopathy/physiopathology , Aged , Aged, 80 and over , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Cohort Studies , Diabetic Retinopathy/prevention & control , Female , Humans , Logistic Models , Male , Medicare/statistics & numerical data , Prevalence , Retrospective Studies , Risk Factors , United States
7.
Biomaterials ; 308: 122545, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38547831

ABSTRACT

Macrophages are key modulators of all inflammatory diseases and essential for their resolution, making macrophage cell therapy a promising strategy for regenerative medicine. However, since macrophages change rapidly in response to microenvironmental cues, their phenotype must be controlled post-administration. We present a tunable biomaterial-based strategy to control macrophages intracellularly via small molecule-releasing microparticles. Poly(lactic-co-glycolic acid) microparticles encapsulating the anti-inflammatory and anti-fibrotic drug dexamethasone were administered to macrophages in vitro, with uptake rates controlled by different loading regimes. Microparticle dose and dexamethasone content directly affected macrophage phenotype and phagocytic capacity, independent of particle content per cell, leading to an overall pro-reparative, anti-inflammatory, anti-fibrotic phenotype with increased phagocytic and ECM degrading functionality. Intracellularly controlled macrophages partially maintained this phenotype in vivo in a murine pulmonary fibrosis model, with more prominent effects in a pro-fibrotic environment compared to pro-inflammatory. These results suggest that intracellular control using biomaterials has the potential to control macrophage phenotype post-administration, which is essential for successful macrophage cell therapy.


Subject(s)
Biocompatible Materials , Dexamethasone , Macrophages , Polylactic Acid-Polyglycolic Acid Copolymer , Animals , Macrophages/metabolism , Macrophages/drug effects , Biocompatible Materials/chemistry , Dexamethasone/pharmacology , Dexamethasone/therapeutic use , Mice , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Cell- and Tissue-Based Therapy/methods , Mice, Inbred C57BL , Inflammation/pathology , Pulmonary Fibrosis/therapy , Pulmonary Fibrosis/pathology , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Phagocytosis/drug effects , RAW 264.7 Cells , Polyglycolic Acid/chemistry , Lactic Acid/chemistry , Fibrosis
8.
Nat Commun ; 15(1): 4235, 2024 May 18.
Article in English | MEDLINE | ID: mdl-38762489

ABSTRACT

Inflammation induced by lung infection is a double-edged sword, moderating both anti-viral and immune pathogenesis effects; the mechanism of the latter is not fully understood. Previous studies suggest the vasculature is involved in tissue injury. Here, we report that expression of Sparcl1, a secreted matricellular protein, is upregulated in pulmonary capillary endothelial cells (EC) during influenza-induced lung injury. Endothelial overexpression of SPARCL1 promotes detrimental lung inflammation, with SPARCL1 inducing 'M1-like' macrophages and related pro-inflammatory cytokines, while SPARCL1 deletion alleviates these effects. Mechanistically, SPARCL1 functions through TLR4 on macrophages in vitro, while TLR4 inhibition in vivo ameliorates excessive inflammation caused by endothelial Sparcl1 overexpression. Finally, SPARCL1 expression is increased in lung ECs from COVID-19 patients when compared with healthy donors, while fatal COVID-19 correlates with higher circulating SPARCL1 protein levels in the plasma. Our results thus implicate SPARCL1 as a potential prognosis biomarker for deadly COVID-19 pneumonia and as a therapeutic target for taming hyperinflammation in pneumonia.


Subject(s)
COVID-19 , Endothelial Cells , Lung , Macrophage Activation , SARS-CoV-2 , Animals , Humans , COVID-19/immunology , COVID-19/virology , COVID-19/metabolism , COVID-19/pathology , Mice , Endothelial Cells/metabolism , Endothelial Cells/virology , Endothelial Cells/immunology , SARS-CoV-2/physiology , Lung/virology , Lung/pathology , Lung/immunology , Toll-Like Receptor 4/metabolism , Toll-Like Receptor 4/genetics , Calcium-Binding Proteins/metabolism , Calcium-Binding Proteins/genetics , Mice, Inbred C57BL , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Pneumonia, Viral/metabolism , Male , Macrophages/metabolism , Macrophages/immunology , Female , Mice, Knockout , Extracellular Matrix Proteins
9.
Sci Transl Med ; 16(732): eadg6229, 2024 Jan 31.
Article in English | MEDLINE | ID: mdl-38295183

ABSTRACT

Disruption of pulmonary vascular homeostasis is a central feature of viral pneumonia, wherein endothelial cell (EC) death and subsequent angiogenic responses are critical determinants of the outcome of severe lung injury. A more granular understanding of the fundamental mechanisms driving reconstitution of lung endothelium is necessary to facilitate therapeutic vascular repair. Here, we demonstrated that TGF-ß signaling through TGF-ßR2 (transforming growth factor-ß receptor 2) is activated in pulmonary ECs upon influenza infection, and mice deficient in endothelial Tgfbr2 exhibited prolonged injury and diminished vascular repair. Loss of endothelial Tgfbr2 prevented autocrine Vegfa (vascular endothelial growth factor α) expression, reduced endothelial proliferation, and impaired renewal of aerocytes thought to be critical for alveolar gas exchange. Angiogenic responses through TGF-ßR2 were attributable to leucine-rich α-2-glycoprotein 1, a proangiogenic factor that counterbalances canonical angiostatic TGF-ß signaling. Further, we developed a lipid nanoparticle that targets the pulmonary endothelium, Lung-LNP (LuLNP). Delivery of Vegfa mRNA, a critical TGF-ßR2 downstream effector, by LuLNPs improved the impaired regeneration phenotype of EC Tgfbr2 deficiency during influenza injury. These studies defined a role for TGF-ßR2 in lung endothelial repair and demonstrated efficacy of an efficient and safe endothelial-targeted LNP capable of delivering therapeutic mRNA cargo for vascular repair in influenza infection.


Subject(s)
Influenza, Human , Humans , Mice , Animals , Receptor, Transforming Growth Factor-beta Type II , Vascular Endothelial Growth Factor A , Lung/metabolism , Transforming Growth Factor beta/metabolism , RNA, Messenger
10.
Conserv Physiol ; 11(1): coad060, 2023.
Article in English | MEDLINE | ID: mdl-37916041

ABSTRACT

Arctic ecosystems are changing rapidly. The tundra supports nesting migratory seabirds that spend most of their year over the ocean. Migrations are demanding, but it is unclear how physiological capability may equip organisms to respond to their changing environments. For two migratory seabird species nesting in Alaska, USA, the Arctic tern (n = 10) and the long-tailed jaeger (n = 8), we compared oxidative physiology and aerobic capacity measured during incubation and we recorded individual movement paths using electronic tracking tags. Within species, we hypothesized that individuals with longer-distance migrations would show higher oxidative stress and display better aerobic capacity than shorter-distance migrants. We examined blood parameters relative to subsequent fall migration in jaegers and relative to previous spring migration in terns. We present the first measurements of oxidative stress in these species and the first migratory movements of long-tailed jaegers in the Pacific Ocean. Arctic terns displayed positive correlation of oxidative variables, or better integration than jaegers. Relative to physiological sampling, pre-breeding northward migration data were available for terns and post-breeding southward data were available for jaegers. Terns reached a farther maximum distance from the colony than jaegers (16 199 ± 275 km versus 10 947 ± 950 km) and rate of travel northward (447 ± 41.8 km/day) was positively correlated with hematocrit, but we found no other relationships. In jaegers, there were no relationships between individuals' physiology and southward rate of travel (193 ± 52.3 km/day) or migratory distance. While it is not clear whether the much longer migrations of the terns is related to their better integration, or to another factor, our results spark hypotheses that could be evaluated through a controlled phylogenetic study. Species with better integration may be less susceptible to environmental factors that increase oxidative stress, including thermal challenges or changes in prey distribution as the Arctic climate changes rapidly.

11.
PLoS One ; 18(3): e0283424, 2023.
Article in English | MEDLINE | ID: mdl-36952485

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) affects almost all countries in the world and it impacts every aspect of people's life-physically, mentally, and socio-economically. There are several research studies examining the impact of this pandemic on health, however, very few studies examining the impact of this pandemic on quality of life. This study aimed to investigate the association between proximity to the COVID-19 and quality of life of healthcare workers and identify factors influencing quality of life. METHODS: A cross-sectional study was conducted among hospital staff in a tertiary hospital in Singapore. Data on demographic, medical history, lifestyle factors, psychosocial factors, and quality of life were collected using online self-administered questionnaire. Quality of life (QoL) was measured by the WHOQOL-BREF questionnaire. Robust linear regression was used to determine factors associated with quality of life. RESULTS: A total of 1911 participants were included in the analysis. The average age of participants was 38.25 (SD = 11.28) years old. 26.90% of participants had been quarantined, hospitalised, being suspected or diagnosed of having COVID-19 infection and they were found to have the lowest levels of QoL across all four domains (physical, psychological, social, and environmental domains). Participants who were singles or nurses, worked in shifts or worked longer hours, had chronic diseases were likely to have lower QoL scores compared to participants in other categories. Healthy lifestyle, social connectivity, resilience, social and workplace support were associated with higher QoL scores. CONCLUSIONS: In planning of measures which aim to improve QoL of healthcare workers, priority should be given to individuals who have been quarantined, hospitalised, being suspected, or diagnosed of having COVID-19 infection. In addition to the proximity of the COVID, lifestyle and psychosocial factors contribute to QoL of healthcare workers. Hence, multifaceted interventions are needed to improve QoL of healthcare workers.


Subject(s)
COVID-19 , Quality of Life , Humans , Adult , Quality of Life/psychology , COVID-19/epidemiology , Cross-Sectional Studies , Health Personnel/psychology , Linear Models , Surveys and Questionnaires
12.
Eur Urol ; 84(4): 393-405, 2023 10.
Article in English | MEDLINE | ID: mdl-37169638

ABSTRACT

CONTEXT: Differences in recovery, oncological, and quality of life (QoL) outcomes between open radical cystectomy (ORC) and robot-assisted radical cystectomy (RARC) for patients with bladder cancer are unclear. OBJECTIVE: This review aims to compare these outcomes within randomized trials of ORC and RARC in this context. The primary outcome was the rate of 90-d perioperative events. The secondary outcomes included operative, pathological, survival, and health-related QoL (HRQoL) measures. EVIDENCE ACQUISITION: Systematic literature searches of MEDLINE, Embase, Web of Science, and clinicaltrials.gov were performed up to May 31, 2022. EVIDENCE SYNTHESIS: Eight trials, reporting 1024 participants, were included. RARC was associated with a shorter hospital length of stay (LOS; mean difference [MD] 0.21, 95% confidence interval [CI] 0.03-0.39, p = 0.02) than and similar complication rates to ORC. ORC was associated with higher thromboembolic events (odds ratio [OR] 1.84, 95% CI 1.02-3.31, p = 0.04). ORC was associated with more blood loss (MD 322 ml, 95% CI 193-450, p < 0.001) and transfusions (OR 2.35, 95% CI 1.65-3.36, p < 0.001), but shorter operative time (MD 76 min, 95% CI 39-112, p < 0.001) than RARC. No differences in lymph node yield (MD 1.07, 95% CI -1.73 to 3.86, p = 0.5) or positive surgical margin rates (OR 0.95, 95% CI 0.54-1.67, p = 0.9) were present. RARC was associated with better physical functioning or well-being (standardized MD 0.47, 95% CI 0.29-0.65, p < 0.001) and role functioning (MD 8.8, 95% CI 2.4-15.1, p = 0.007), but no improvement in overall HRQoL. No differences in progression-free survival or overall survival were seen. Limitations may include a lack of generalization given trial patients. CONCLUSIONS: RARC offers various perioperative benefits over ORC. It may be more suitable in patients wishing to avoid blood transfusion, those wanting a shorter LOS, or those at a high risk of thromboembolic events. PATIENT SUMMARY: This study compares robot-assisted keyhole surgery with open surgery for bladder cancer. The robot-assisted approach offered less blood loss, shorter hospital stays, and fewer blood clots. No other differences were seen.


Subject(s)
Robotic Surgical Procedures , Robotics , Urinary Bladder Neoplasms , Humans , Cystectomy/adverse effects , Quality of Life , Treatment Outcome , Postoperative Complications/etiology , Randomized Controlled Trials as Topic , Urinary Bladder Neoplasms/pathology , Robotic Surgical Procedures/adverse effects
13.
bioRxiv ; 2023 May 25.
Article in English | MEDLINE | ID: mdl-37292817

ABSTRACT

Inflammation upon infectious lung injury is a double-edged sword: while tissue-infiltrating immune cells and cytokines are necessary to control infection, these same factors often aggravate injury. Full appreciation of both the sources and targets of inflammatory mediators is required to facilitate strategies to maintain antimicrobial effects while minimizing off-target epithelial and endothelial damage. Recognizing that the vasculature is centrally involved in tissue responses to injury and infection, we observed that pulmonary capillary endothelial cells (ECs) exhibit dramatic transcriptomic changes upon influenza injury punctuated by profound upregulation of Sparcl1 . Endothelial deletion and overexpression of SPARCL1 implicated this secreted matricellular protein in driving key pathophysiologic symptoms of pneumonia, which we demonstrate result from its effects on macrophage polarization. SPARCL1 induces a shift to a pro-inflammatory "M1-like" phenotype (CD86 + CD206 - ), thereby increasing associated cytokine levels. Mechanistically, SPARCL1 acts directly on macrophages in vitro to induce the pro-inflammatory phenotype via activation of TLR4, and TLR4 inhibition in vivo ameliorates inflammatory exacerbations caused by endothelial Sparcl1 overexpression. Finally, we confirmed significant elevation of SPARCL1 in COVID-19 lung ECs in comparison with those from healthy donors. Survival analysis demonstrated that patients with fatal COVID-19 had higher levels of circulating SPARCL1 protein compared to those who recovered, indicating the potential of SPARCL1 as a biomarker for prognosis of pneumonia and suggesting that personalized medicine approaches might be harnessed to block SPARCL1 and improve outcomes in high-expressing patients.

14.
Chemistry ; 18(50): 16073-89, 2012 Dec 07.
Article in English | MEDLINE | ID: mdl-23086615

ABSTRACT

48 new hydrogen-bonded complexes have been prepared by combining 16 fluorophenols of general formula C(6)F(n)H(5-n)OH with three different alkoxystilbazoles (butyloxy-, octyloxy- and dodecyloxy-). Single-crystal X-ray structures were obtained for 10 of the 16 complexes of octyloxystilbazole from which it was found that most of the structures could be collected into one of two groups according to both the motif shown by the complex and by the solid-state packing. Because all but one crystallised in the P1 space group, meaningful comparisons could be drawn and it was observed that six structures were extremely close in nature so that significant molecular overlap was found. On this basis, doubt is cast on the significance of some of the weaker intermolecular contacts found in the solid state. 40 of the new complexes showed liquid-crystal properties and it was found that although complexes of butyloxystilbazole were all nematic, almost all of those with dodecyloxystilbazole showed a smectic A (SmA) phase. Complexes of octyloxystilbazole showed a mixture of both. Structure/property correlations showed that clearing points were independent of the pK(a) of the phenol. The most stable mesophases were found when the fluorophenol contained a fluorine at the 2-position, which was interpreted in terms of the formation of an intramolecular H⋅⋅⋅F hydrogen bond to give a six-membered ring linking the two components into a stable, coplanar conformation. The least stable mesophases were found when no such ring formation was possible and the phenol was relatively free to move.

15.
Korean J Anesthesiol ; 75(1): 47-60, 2022 02.
Article in English | MEDLINE | ID: mdl-34619855

ABSTRACT

BACKGROUND: Diabetes is a risk factor for postoperative complications. Previous meta-analyses have shown that elevated glycated hemoglobin (HbA1c) levels are associated with postoperative complications in various surgical populations. However, this is the first meta-analysis to investigate the association between preoperative HbA1c levels and postoperative complications in patients undergoing elective major abdominal surgery. METHODS: PRISMA guidelines were adhered to for this study. Six databases were searched up to April 1, 2020. Primary studies investigating the effect of HbA1c levels on postoperative complications after elective major abdominal surgery were included. Risk of bias and quality of evidence assessments were performed. Data were pooled using a random effects model. Meta-regression was performed to evaluate different HbA1c cut-off values. RESULTS: Twelve observational studies (25,036 patients) were included. Most studies received a 'good' and 'moderate quality' score using the NOS and GRADE, respectively. Patients with a high HbA1c had a greater risk of anastomotic leaks (odds ratio [OR]: 2.80, 95% CI [1.63, 4.83], P < 0.001), wound infections (OR: 1.21, 95% CI [1.08, 1.36], P = 0.001), major complications defined as Clavien-Dindo [CD] 3-5 (OR: 2.16, 95% CI [1.54, 3.01], P < 0.001), and overall complications defined as CD 1-5 (OR: 2.12, 95% CI [1.48, 3.04], P < 0.001). CONCLUSIONS: An HbA1c between 6% and 7% is associated with higher risks of anastomotic leaks, wound infections, major complications, and overall postoperative complications. Therefore, guidelines with an HbA1c threshold > 7% may be putting pre-optimized patients at risk. Future randomized controlled trials are needed to explore causation before policy changes are made.


Subject(s)
Diabetes Mellitus , Elective Surgical Procedures , Abdomen/surgery , Diabetes Mellitus/epidemiology , Elective Surgical Procedures/adverse effects , Glycated Hemoglobin/analysis , Humans , Postoperative Complications/epidemiology , Postoperative Complications/etiology
16.
Cell Rep ; 41(11): 111805, 2022 12 13.
Article in English | MEDLINE | ID: mdl-36516758

ABSTRACT

The lung exhibits a robust, multifaceted regenerative response to severe injuries such as influenza infection, during which quiescent lung-resident epithelial progenitors participate in two distinct reparative pathways: functionally beneficial regeneration via alveolar type 2 (AT2) cell proliferation and differentiation, and dysplastic tissue remodeling via intrapulmonary airway-resident basal p63+ progenitors. Here we show that the basal cell transcription factor ΔNp63 is required for intrapulmonary basal progenitors to participate in dysplastic alveolar remodeling following injury. We find that ΔNp63 restricts the plasticity of intrapulmonary basal progenitors by maintaining either active or repressive histone modifications at key differentiation gene loci. Following loss of ΔNp63, intrapulmonary basal progenitors are capable of either airway or alveolar differentiation depending on their surrounding environment both in vitro and in vivo. Uncovering these regulatory mechanisms of dysplastic repair and lung basal cell fate choice highlight potential therapeutic targets to promote functional alveolar regeneration following severe lung injuries.


Subject(s)
Influenza, Human , Lung Injury , Humans , Alveolar Epithelial Cells/metabolism , Lung/metabolism , Cell Differentiation , Influenza, Human/metabolism , Epithelial Cells/metabolism
17.
Langmuir ; 27(7): 3254-60, 2011 Apr 05.
Article in English | MEDLINE | ID: mdl-21401065

ABSTRACT

Aqueous foams stabilized by ceramic and thermoplastic polymeric particles provide a general method for producing novel porous materials because their extraordinary stability against disproportionation and drainage allows them to be dried and sintered into solid materials. Here, we report the different microstructures that can be obtained from liquid foams stabilized by binary mixtures of particles when the interfacial energies between the particles and the air-liquid interfaces are manipulated to promote either preferential or competitive self-assembly of the particles at the foam interface. Modification of the interfacial energies was accomplished through surface modification of the particles or by decreasing the surface tension of the aqueous phase. Materials derived from liquid foams stabilized by poly(vinylidene fluoride) (PVDF) and alumina (Al(2)O(3)) particles are investigated. However, as is shown, the method can be extended to other polymeric and ceramic particles and provides the possibility to manufacture a wide range of porous composite materials.

18.
J Vasc Surg Venous Lymphat Disord ; 9(2): 510-524.e4, 2021 03.
Article in English | MEDLINE | ID: mdl-33227458

ABSTRACT

OBJECTIVE: Absorbable inferior vena cava filters (IVCFs) could be more effective and safer than standard IVCFs in theory, as they will self-resorb over time, thus rendering the need for filter retrieval and the risks associated with it unnecessary. This scoping review aims to evaluate the design of current absorbable IVCFs, review the development phase of the absorbable IVCFs, assess the efficacy of the absorbable IVCFs and their complications, and discuss the limitations and areas for future research. METHODS: MEDLINE, PubMed, and Embase databases were electronically searched and citations of relevant studies manually searched. Study selection and data extraction were performed by two independent reviewers using predetermined criteria and stored on premade proforma, respectively. The risk of bias (RoB) for both in vitro and in vivo studies were performed using established RoB tools. RESULTS: Eight studies were suitable for inclusion in this scoping review; five were in vivo and three were in vitro studies. No clinical trials were found. The RoB varied from moderate to high for in vivo studies and from low to moderate for in vitro studies. Overall, there was evidence from both in vivo and in vitro studies that absorbable IVCFs were effective in clot capturing and self-resorption and could decrease complications associated with standard IVCFs. However, there was a broad lack of statistical analyses and control groups to determine the significance of these findings. CONCLUSIONS: Absorbable IVCFs have shown promising features and results in preclinical models. However, significant research needs to be further performed to achieve the ideal characteristics of an absorbable IVCF before the first human trial can be conducted safely.


Subject(s)
Absorbable Implants , Prosthesis Implantation/instrumentation , Vena Cava Filters , Venous Thromboembolism/prevention & control , Absorbable Implants/adverse effects , Animals , Humans , Prosthesis Design , Prosthesis Implantation/adverse effects , Risk Factors , Time Factors , Vena Cava Filters/adverse effects
19.
Front Cell Dev Biol ; 9: 654385, 2021.
Article in English | MEDLINE | ID: mdl-33898453

ABSTRACT

Rod and cone photoreceptors differ in their shape, photopigment expression, synaptic connection patterns, light sensitivity, and distribution across the retina. Although rods greatly outnumber cones, human vision is mostly dependent on cone photoreceptors since cones are essential for our sharp visual acuity and color discrimination. In humans and other primates, the fovea centralis (fovea), a specialized region of the central retina, contains the highest density of cones. Despite the vast importance of the fovea for human vision, the molecular mechanisms guiding the development of this region are largely unknown. MicroRNAs (miRNAs) are small post-transcriptional regulators known to orchestrate developmental transitions and cell fate specification in the retina. Here, we have characterized the transcriptional landscape of the developing rhesus monkey retina. Our data indicates that non-human primate fovea development is significantly accelerated compared to the equivalent retinal region at the other side of the optic nerve head, as described previously. Notably, we also identify several miRNAs differentially expressed in the presumptive fovea, including miR-15b-5p, miR-342-5p, miR-30b-5p, miR-103-3p, miR-93-5p as well as the miRNA cluster miR-183/-96/-182. Interestingly, miR-342-5p is enriched in the nasal primate retina and in the peripheral developing mouse retina, while miR-15b is enriched in the temporal primate retina and increases over time in the mouse retina in a central-to-periphery gradient. Together our data constitutes the first characterization of the developing rhesus monkey retinal miRNome and provides novel datasets to attain a more comprehensive understanding of foveal development.

20.
Arch Womens Ment Health ; 13(3): 207-14, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20372948

ABSTRACT

We examined the variables associated with HIV stigma in HIV-positive women currently living in Ontario, Canada. Based on previous literature, we predicted that variables of social marginalization (e.g., ethnicity, income, education), medical variables (e.g., higher CD4 count, lower viral load), and increased psychological distress would be associated with higher perceived HIV stigma among HIV-positive women. One hundred fifty-nine HIV-positive women between the ages of 18 and 52 in Ontario completed self-report measures of the aforementioned variables. Women were recruited through 28 AIDS service organizations, eight HIV clinics, and two community health centers. In multiple regression analyses, for women born in Canada, lower educational level and higher anxiety were associated with higher HIV stigma. For women born outside of Canada, having been judged by a physician in Canada for trying to become pregnant was associated with higher HIV stigma. For HIV-positive women born outside of Canada, negative judgment by a physician regarding intentions to become pregnant should be addressed to reduce perceived HIV stigma and vice versa. Health care providers should be trained in the provision of sensitive and effective health care for women living with HIV, especially when providing reproductive health care.


Subject(s)
HIV Infections/psychology , Pregnancy/psychology , Prejudice , Stress, Psychological/etiology , Adult , Attitude of Health Personnel , Family Relations , Female , Humans , Middle Aged , Ontario , Regression Analysis , Risk Factors , Socioeconomic Factors , Viral Load
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