Geometrical analysis identified morphological features of hydrogel-induced cancer stem cells in synovial sarcoma model cells.

Cancer stem cells (CSCs) has been a key target to cure cancer patients completely. Although many CSC markers have been identified, they are frequently cancer type-specific and those expressions are occasionally variable, which becomes an obstacle to elucidate the characteristics of the CSCs. Here we scrutinized the relationship between stemness elevation and geometrical features of single cells. The PAMPS hydrogel was utilized to create the CSCs from mouse myoblast C2C12 and its synovial sarcoma model cells. qRT-PCR analysis confirmed the significant increase in expression levels of Sox2, Nanog, and Oct3/4 on the PAMPS gel, which was higher in the synovial sarcoma model cells. Of note, the morphological heterogeneity was appeared on the PAMPS gel, mainly including flat spreading, elongated spindle, and small round cells, and the Sox2 expression was highest in the small round cells. To examine the role of morphological differences in the elevation of stemness, over 6,400 cells were segmented along with the Sox2 intensity, and 12 geometrical features were extracted at single cell level. A nonlinear mapping of the geometrical features by using uniform manifold approximation and projection (UMAP) clearly revealed the existence of relationship between morphological differences and the stemness elevation, especially for C2C12 and its synovial sarcoma model on the PAMPS gel in which the small round cells possess relatively high Sox2 expression on the PAMPS gel, which supports the strong relationship between morphological changes and the stemness elevation. Taken together, these geometrical features can be useful for morphological profiling of CSCs to classify and distinguish them for understanding of their role in disease progression and drug discovery.

Anopheles coluzzii stearoyl-CoA desaturase is essential for adult female survival and reproduction upon blood feeding.

Vitellogenesis and oocyte maturation require anautogenous female Anopheles mosquitoes to obtain a bloodmeal from a vertebrate host. The bloodmeal is rich in proteins that are readily broken down into amino acids in the midgut lumen and absorbed by the midgut epithelial cells where they are converted into lipids and then transported to other tissues including ovaries. The stearoyl-CoA desaturase (SCD) plays a pivotal role in this process by converting saturated (SFAs) to unsaturated (UFAs) fatty acids; the latter being essential for maintaining cell membrane fluidity amongst other housekeeping functions. Here, we report the functional and phenotypic characterization of SCD1 in the malaria vector mosquito Anopheles coluzzii. We show that RNA interference (RNAi) silencing of SCD1 and administration of sterculic acid (SA), a small molecule inhibitor of SCD1, significantly impact on the survival and reproduction of female mosquitoes following blood feeding. Microscopic observations reveal that the mosquito thorax is quickly filled with blood, a phenomenon likely caused by the collapse of midgut epithelial cell membranes, and that epithelial cells are depleted of lipid droplets and oocytes fail to mature. Transcriptional profiling shows that genes involved in protein, lipid and carbohydrate metabolism and immunity-related genes are the most affected by SCD1 knock down (KD) in blood-fed mosquitoes. Metabolic profiling reveals that these mosquitoes exhibit increased amounts of saturated fatty acids and TCA cycle intermediates, highlighting the biochemical framework by which the SCD1 KD phenotype manifests as a result of a detrimental metabolic syndrome. Accumulation of SFAs is also the likely cause of the potent immune response observed in the absence of infection, which resembles an auto-inflammatory condition. These data provide insights into mosquito bloodmeal metabolism and lipid homeostasis and could inform efforts to develop novel interventions against mosquito-borne diseases.

Differentiability of cell types enhanced by detrending a non-homogeneous pattern in a line-illumination Raman microscope.

A line illumination Raman microscope extracts the underlying spatial and spectral information of a sample, typically a few hundred times faster than raster scanning. This makes it possible to measure a wide range of biological samples such as cells and tissues - that only allow modest intensity illumination to prevent potential damage - within feasible time frame. However, a non-uniform intensity distribution of laser line illumination may induce some artifacts in the data and lower the accuracy of machine learning models trained to predict sample class membership. Here, using cancerous and normal human thyroid follicular epithelial cell lines, FTC-133 and Nthy-ori 3-1 lines, whose Raman spectral difference is not so large, we show that the standard pre-processing of spectral analyses widely used for raster scanning microscopes introduced some artifacts. To address this issue, we proposed a detrending scheme based on random forest regression, a nonparametric model-free machine learning algorithm, combined with a position-dependent wavenumber calibration scheme along the illumination line. It was shown that the detrending scheme minimizes the artifactual biases arising from non-uniform laser sources and significantly enhances the differentiability of the sample states, i.e., cancerous or normal epithelial cells, compared to the standard pre-processing scheme.

Comparative Evaluation of the Effects of Amorphous Silica Nanoparticles on the Erythrocytes of Wistar Normotensive and Spontaneously Hypertensive Rats.

Silica nanoparticles (SiNPs) are one of the most widely used nanomaterials. SiNPs can encounter erythrocytes and hypertension is strongly linked to abnormalities in the functional and structural characteristics of erythrocytes. As little is known about the combinatorial effect of SiNP-hypertension interactions on erythrocytes, the aim of this work was to study the effects triggered by hypertension on SiNPs induced hemolysis and the pathophysiological mechanism underlying it. We compared the interaction of amorphous 50 nm SiNPs at various concentrations (0.2, 1, 5 and 25 µg/mL) with erythrocytes of normotensive (NT) and hypertensive (HT) rats in vitro. Following incubation of the erythrocytes, SiNPs induced significant and dose-dependent increase in hemolysis. Transmission electron microscopy revealed erythrocyte deformity in addition to SiNPs taken up by erythrocytes. The erythrocyte susceptibility to lipid peroxidation was significantly increased. The concentration of reduced glutathione, and activities of superoxide dismutase, and catalase were significantly increased. SiNPs significantly increased intracellular Ca2+. Likewise, the concentration of the cellular protein annexin V and calpain activity was enhanced by SiNPs. Concerningly, all the tested parameters were significantly enhanced in erythrocytes from HT rats compared to NT rats. Our results collectively demonstrate that hypertension can potentially exacerbate the in vitro effect induced by SiNPs.

Impact of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccination and Pediatric Age on Delta Variant Household Transmission.

BACKGROUND: In Singapore, quarantine of all close contacts with entry and exit polymerase chain reaction testing enabled evaluation of the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and pediatric age on transmission of the Delta variant. METHODS: This retrospective cohort study included all household close contacts between 1 March 2021 and 31 August 2021. RESULTS: Among 8470 Delta variant-exposed contacts linked to 2583 indices, full-vaccination of the index with BNT162b2 or mRNA-1273 was associated with reduction in acquisition by contacts (adjusted odds ratio [aOR], 0.56; 95% robust confidence interval [RCI], .44-.71 and aOR, 0.51; 95% RCI, .27-.96, respectively). Compared with young adults (aged 18-29 years), children (aged 0-11 years) were significantly more likely to transmit (aOR, 2.37; 95% RCI, 1.57-3.60) and acquire (aOR, 1.43; 95% RCI, 1.07-1.93) infection, vaccination considered. Longer duration from vaccination completion among contacts was associated with decline in protection against acquisition (first-month aOR, 0.42; 95% RCI, .33-.55; fifth-month aOR, 0.84; 95% RCI, .55-.98; P < .0001 for trend) and symptomatic disease (first-month aOR, 0.30; 95% RCI, .23-.41; fifth-month aOR, 0.62; 95% RCI, .38-1.02; P < .0001 for trend). Contacts immunized with mRNA-1273 had significant reduction in acquisition (aOR, 0.73; 95% RCI, .58-.91) compared with BNT162b2. CONCLUSIONS: Among household close contacts, vaccination prevented onward SARS-CoV-2 transmission and there was in-creased risk of SARS-CoV-2 acquisition and transmission among children compared with young adults. Time after completion of vaccination and vaccine type affected SARS-CoV-2 acquisition.

Probiotics, prebiotics and synbiotics improved the functionality of aquafeed: Upgrading growth, reproduction, immunity and disease resistance in fish.

Aquaculture plays an increasingly significant role in improving the sustainability of global fish production. This sector has been intensified with the advent of new husbandry practices and the development of new technology. However, the increasing intensification and indiscriminate commercialized farming has enhanced the vulnerability of cultivated aquatic species to damage from pathogens. In efforts to confront these various diseases, frequent use of drugs, antibiotics, chemotherapeutics, and agents for sterilization have unintentionally added to the risk of transmission of pathogens and harmful chemical compounds to consumers. Some natural dietary supplements are believed to have the potential to offset this setback in aquaculture. Application of bio-friendly feed additives such as probiotics, prebiotics and synbiotics are becoming popular dietary supplements with the potential to not only improve growth performance, but in some cases can also enhance immune competence and the overall well-being of fish and crustaceans. The present review discusses and summarizes the effects of probiotics, prebiotics and synbiotics application on growth, stress mitigation, microbial composition of intestine, immune system and health condition of aquatic animals in association with existing constraints and future perspectives in aquaculture.

Imported Monkeypox, Singapore.

In May 2019, we investigated monkeypox in a traveler from Nigeria to Singapore. The public health response included rapid identification of contacts, use of quarantine, and postexposure smallpox vaccination. No secondary cases were identified. Countries should develop surveillance systems to detect emerging infectious diseases globally.

Health Impact of Silver Nanoparticles: A Review of the Biodistribution and Toxicity Following Various Routes of Exposure.

Engineered nanomaterials (ENMs) have gained huge importance in technological advancements over the past few years. Among the various ENMs, silver nanoparticles (AgNPs) have become one of the most explored nanotechnology-derived nanostructures and have been intensively investigated for their unique physicochemical properties. The widespread commercial and biomedical application of nanosilver include its use as a catalyst and an optical receptor in cosmetics, electronics and textile engineering, as a bactericidal agent, and in wound dressings, surgical instruments, and disinfectants. This, in turn, has increased the potential for interactions of AgNPs with terrestrial and aquatic environments, as well as potential exposure and toxicity to human health. In the present review, after giving an overview of ENMs, we discuss the current advances on the physiochemical properties of AgNPs with specific emphasis on biodistribution and both in vitro and in vivo toxicity following various routes of exposure. Most in vitro studies have demonstrated the size-, dose- and coating-dependent cellular uptake of AgNPs. Following NPs exposure, in vivo biodistribution studies have reported Ag accumulation and toxicity to local as well as distant organs. Though there has been an increase in the number of studies in this area, more investigations are required to understand the mechanisms of toxicity following various modes of exposure to AgNPs.

Pulmonary exposure to silver nanoparticles impairs cardiovascular homeostasis: Effects of coating, dose and time.

Pulmonary exposure to silver nanoparticles (AgNPs) revealed the potential of nanoparticles to cause pulmonary toxicity, cross the alveolar-capillary barrier, and distribute to remote organs. However, the mechanism underlying the effects of AgNPs on the cardiovascular system remains unclear. Hence, we investigated the cardiovascular mechanisms of pulmonary exposure to AgNPs (10 nm) with varying coatings [polyvinylpyrrolidone (PVP) and citrate (CT)], concentrations (0.05, 0.5 and 5 mg/kg body weight), and time points (1 and 7 days) in BALB/C mice. Silver ions (Ag+) were used as ionic control. Exposure to AgNPs induced lung inflammation. In heart, tumor necrosis factor α, interleukin 6, total antioxidants, reduced glutathione and 8-isoprostane significantly increased for both AgNPs. Moreover, AgNPs caused oxidative DNA damage and apoptosis in the heart. The plasma concentration of fibrinogen, plasminogen activation inhibitor-1 and brain natriuretic peptide were significantly increased for both coating AgNPs. Likewise, the prothrombin time and activated partial thromboplastin time were significantly decreased. Additionally, the PVP- and CT- AgNPs induced a significant dose-dependent increase in thrombotic occlusion time in cerebral microvessels at both time points. In vitro study on mice whole blood exhibited significant platelet aggregation for both particle types. Compared with AgNPs, Ag+ increased thrombogenicity and markers of oxidative stress, but did not induce either DNA damage or apoptosis in the heart. In conclusion, pulmonary exposure to AgNPs caused cardiac oxidative stress, DNA damage and apoptosis, alteration of coagulation markers and thrombosis. Our findings provide a novel mechanistic insight into the cardiovascular pathophysiological effects of lung exposure to AgNPs.

The in Vitro Effect of Polyvinylpyrrolidone and Citrate Coated Silver Nanoparticles on Erythrocytic Oxidative Damage and Eryptosis.

BACKGROUND/AIMS: Silver nanoparticles (AgNPs) are increasingly used as antimicrobial agents and drug carriers in various biomedical fields. AgNPs can encounter erythrocytes either directly following intravenous injection, or indirectly via translocation from the site of administration. However, information regarding the pathophysiological effects and possible mechanism of action of AgNPs on the erythrocytes are still inadequately studied. Thus, the aim of our study was to investigate the mechanism underlying the effect of coating and concentration of AgNPs on mouse erythrocytes in vitro. METHODS: We studied the interaction of polyvinylpyrrolidone (PVP) and citrate (CT) coated AgNPs (10 nm) at various concentrations (2.5, 10, 40 µg/ml) with mouse erythrocytes in vitro using various techniques including transmission electron microscopy (TEM), hemolysis, and colorimetric measurement of markers of oxidative stress comprising malondialdehyde (MDA), reduced glutathione (GSH), and catalase (CAT). Intracellular calcium (Ca2+) was determined using Fura 2AM fluorescence. Annexin V was quantified using ELISA and the caspase 3 was determined both flurometrically and by western blot technique. RESULTS: Following incubation of the erythrocytes with AgNPs, both PVP- and CT- AgNPs induced significant and dose - dependent increase in hemolysis. TEM revealed that both PVP- and CT- AgNPs were taken up by erythrocytes. The erythrocyte susceptibility to lipid peroxidation measured by MDA was significantly increased in both PVP-and CT- AgNPs. The concentration of GSH and CAT activity were significantly decreased by both types of AgNPs. Additionally, PVP- and CT- AgNPs significantly increased intracellular Ca2+ in a dose -dependent manner. Likewise, the concentration of the cellular protein annexin V was significantly and dose - dependently enhanced by both types of AgNPs. Furthermore, PVP- and CT- AgNPs induced significant increase in calpain activity in incubated erythrocytes. CONCLUSION: We conclude that both PVP- and CT- AgNPs causes hemolysis, and are taken up by erythrocytes. Moreover, we demonstrated that AgNPs induces oxidative stress and eryptosis. These findings provide evidence for the potential pathophysiological effect of PVP-and CT- AgNPs on erythrocyte physiology.

Sex-related differences in matrix remodeling and early osteogenic markers in aortic valvular interstitial cells.

Calcific aortic valve disease (CAVD) is a major cardiovascular disorder in the developed countries. Male is a known risk factor in this disease; unfortunately, how sex contributes to CAVD is mostly unknown. The objective of this study is to determine whether valvular interstitial cells (VICs) isolated from male versus female aortic valves demonstrate difference in osteogenic differentiation and/or extracellular matrix (ECM) remodeling. VICs were isolated from male and female rat or porcine aortic valves and cultured in osteogenic media for 10, 15 and 20 days. The proliferation among male and female VICs was assessed by a cell growth assay. The matrix remodeling of the VIC samples was quantified using glycosaminoglycan (GAG), collagen type I and gelatin zymography assays. Early osteogenic marker expression was assessed using alkaline phosphatase (ALP) staining and enzyme activity assay and Alizarin Red S staining. Our result showed that proliferation of VICs was significantly greater in female than male after 12 days of culture in regular media. Additionally, male VICs showed elevated amounts of normalized GAG, collagen I, and activated matrix metallopreoteniase-2 expression compared to female. Similarly, ALP content was greater in male VICs than female at all time points. In addition, male VICs formed calcific nodules with greater size, % area and integrated density than females. The results from this research suggest that there is a sex-related difference in the events associated with osteogenic differentiation of the aortic VICs, where male VICs are more prone to calcification.

Exposure to Waterpipe Smoke Disrupts Erythrocyte Homeostasis of BALB/c Mice.

The prevalence of waterpipe tobacco smoking (WPS) is increasing worldwide and is relatively high among youth and young adults. It has been shown, both experimentally and clinically, that WPS exposure adversely affects the cardiovascular and hematological systems through the generation of oxidative stress and inflammation. Our study aimed to evaluate the impact of WPS exposure on erythrocytes, a major component of the hematological system, of BALB/c mice. Here, we assessed the effect of nose-only WPS exposure for four consecutive weeks on erythrocyte inflammation, oxidative stress, and eryptosis. The duration of the session was 30 min/day, 5 days/week. Control mice were exposed to air. Our results showed that the levels of C-reactive protein, lipid peroxidation (LPO), superoxide dismutase, and total nitric oxide (NO) were significantly increased in the plasma of WPS-exposed mice. The number of erythrocytes and the hematocrit were significantly decreased in WPS-exposed mice compared with the control group. Moreover, there was an increase in the erythrocyte fragility in mice exposed to WPS compared with those exposed to air. The levels of lactate dehydrogenase, LPO, reduced glutathione, catalase, and NO were significantly increased in the red blood cells (RBCs) of WPS-exposed mice. In addition, erythrocytes of the WPS-exposed group showed a significant increase in ATPase activity, Ca2+, annexin V binding, and calpain activity. Taken together, our findings suggest that WPS exposure elevated inflammation and oxidative stress in the plasma and induced hemolysis in vivo. It also caused alterations of RBCs oxidative stress and eryptosis in vitro. Our data confirm the detrimental impact of WPS on erythrocyte physiology.

Mosquito immune cells enhance dengue and Zika virus dissemination in Aedes aegypti.

Mosquito-borne viruses cause more than 400 million annual infections and place over half of the world's population at risk. Despite this importance, the mechanisms by which arboviruses infect the mosquito host and disseminate to tissues required for transmission are not well understood. Here, we provide evidence that mosquito immune cells, known as hemocytes, play an integral role in the dissemination of dengue virus (DENV) and Zika virus (ZIKV) in the mosquito Aedes aegypti. We establish that phagocytic hemocytes are a focal point for virus infection and demonstrate that these immune cell populations facilitate virus dissemination to the ovaries and salivary glands. Additional transfer experiments confirm that virus-infected hemocytes confer a virus infection to non-infected mosquitoes more efficiently than free virus in acellular hemolymph, revealing that hemocytes are an important tropism to enhance virus dissemination in the mosquito host. These data support a "trojan horse" model of virus dissemination where infected hemocytes transport virus through the hemolymph to deliver virus to mosquito tissues required for transmission and parallels vertebrate systems where immune cell populations promote virus dissemination to secondary sites of infection. In summary, this study significantly advances our understanding of virus infection dynamics in mosquitoes and highlights conserved roles of immune cells in virus dissemination across vertebrate and invertebrate systems.

Strain magnitude-dependent calcific marker expression in valvular and vascular cells.

Aortic valve disease and atherosclerosis tend to coexist in most patients with cardiovascular disease; however, the causes and mechanisms of disease development in heart valves are still not clearly understood. To understand the contributions of the magnitude of cyclic strain (5% hypotension, 10% physiological, and 15% hypertension) in calcification, we used a model system of tissue-engineered collagen gels containing human aortic smooth muscle cells and human aortic valvular interstitial cells, both isolated from noncalcific heart transplant tissue. The compacted collagen gels were cultured in osteogenic media for 3 weeks in a custom-designed bioreactor and all assessments were performed at the end of the culture period. The major finding of this study is that bone morphogenic protein (BMP)-2 and BMP-4 and transforming growth factor-ß1 mRNA expression significantly changed in response to the magnitude of applied strain in valvular cells, while the lowest expression was observed for the representative physiological strain. On the other hand, mRNA expression in vascular cells did not vary in response to the magnitude of strain. Regarding BMP-2 and BMP-4 protein expression determined by immunostaining, trends were similar to mRNA expression in vascular and valvular cells, where only valvular cells showed a varied protein expression depending on the magnitude of the strain applied. Our results suggest that cellular differences exist between vascular and valvular cells in their response to altered levels of cyclic strain during calcification.

Role of community-level emergency contraceptive pills awareness and possibilities of long-acting reversible or permanent methods in reducing unwanted births in Bangladesh: evidence from a nationwide cross-sectional survey.

OBJECTIVE: This study aims to investigate the role of community-level emergency contraceptive pill (ECP) awareness in reducing unwanted births (UWBs) in Bangladesh and explore the regional variation in women's appropriateness to adopt long-acting reversible contraceptives or permanent methods (LARCPMs) based on their child desire. DESIGN, SETTINGS AND PARTICIPANTS: We used data from the cross-sectional Bangladesh Demographic and Health Survey 2017-2018. We analysed the planning status of the last live birth 3 years preceding the survey of 20,127 ever-married women of reproductive age. METHODS: Considering women were nested within clusters, a mixed-effect multiple logistic regression was implemented to investigate the association between community-level ECP awareness and UWB by controlling for the effects of contextual, individual, and household characteristics. RESULTS: Only 3.7% of women belonged to communities with high ECP awareness. At the national level, 2% of women had UWB. About 2.1% of women who resided in communities of low ECP awareness had UWB, while UWB was only 0.5% among women residing in high ECP awareness communities. The odds of UWB was 71% lower among women who resided in high ECP awareness communities than among those who resided in communities with low ECP awareness. However, community-level ECP awareness could not avert mistimed birth. Dhaka, Chattogram and Rangpur held the highest share of UWB. Fertility persisted for 89% of the women who wanted no more children. Among women who wanted no more children, 15% were not using any method, 13% used traditional family planning methods and only 13% adopted LARCPM. These women mostly resided in Dhaka, followed by Chattogram and Rajshahi. CONCLUSION: This study highlights the significant positive role of ECP awareness in reducing UWB in Bangladesh. Findings may inform policies aimed at increasing LARCPM adoption, particularly among women residing in Dhaka and Chattogram who want no more children.

Increased blood meal size and feeding frequency compromise Aedes aegypti midgut integrity and enhance dengue virus dissemination.

Aedes aegypti is a highly efficient vector for numerous pathogenic arboviruses including dengue virus (DENV), Zika virus, and yellow fever virus. This efficiency can in part be attributed to their frequent feeding behavior. We previously found that acquisition of a second, full, non-infectious blood meal could accelerate virus dissemination within the mosquito by temporarily compromising midgut basal lamina integrity; however, in the wild, mosquitoes are often interrupted during feeding and only acquire partial or minimal blood meals. To explore the impact of this feeding behavior further, we examined the effects of partial blood feeding on DENV dissemination rates and midgut basal lamina damage in Ae. aegypti. DENV-infected mosquitoes given a secondary partial blood meal had intermediate rates of dissemination and midgut basal lamina damage compared to single-fed and fully double-fed counterparts. Subsequently, we evaluated if basal lamina damage accumulated across feeding episodes. Interestingly, within 24 hours of feeding, damage was proportional to the number of blood meals imbibed; however, this additive effect returned to baseline levels by 96 hours. These data reveal that midgut basal lamina damage and rates of dissemination are proportional to feeding frequency and size, and further demonstrate the impact that mosquito feeding behavior has on vector competence and arbovirus epidemiology. This work has strong implications for our understanding of virus transmission in the field and will be useful when designing laboratory experiments and creating more accurate models of virus spread and maintenance.

Magnetic Targeting of Gadolinium Contrast to Enhance MRI of the Inner Ear in Endolymphatic Hydrops.

OBJECTIVES: 1. Determine the feasibility and efficiency of local magnetic targeting delivery of gadolinium (Gad) contrast to the inner ear in rodents. 2. Assess any potential ototoxicity of magnetic targeting delivery of Gad in the inner ear. 3. Study the utility of magnetic targeting delivery of Gad to visualize and quantify endolymphatic hydrops (EH) in a transgenic mouse model. STUDY DESIGN: Controlled in vivo animal model study. METHODS: Paramagnetic Gad was locally delivered to the inner ear using the magnetic targeting technique in both rat and mouse models. Efficiency of contrast delivery was assessed using magnetic resonance imaging (MRI). Ototoxicity of Gad was examined with histology of the cochlea and functional audiological tests. The Phex mouse model was used to study EH, hearing loss, and balance dysfunction. Magnetic targeting delivery of Gad contrast was used in the Phex mouse model to visualize the effects of EH using MRI. RESULTS: Magnetic targeting improved the delivery of Gad to the inner ear and the technique was reproducible in both rat and mouse models. The delivery method did not result in microstructural damage or any significant hearing loss in a normal animal. Magnetic targeting of Gad in the Phex mouse model allowed detailed visualization and quantification of EH. CONCLUSION: This study provided the first evidence of the effectiveness and efficiency of the local magnetic targeting delivery of gadolinium contrast to the inner ear and its application to the visualization and quantification of EH. Laryngoscope, 133:914-923, 2023.

Assessment of COVID-19 management and its consequences on healthcare professionals: a cross-sectional study from Bangladesh.

OBJECTIVE: This explorative study aims to identify the gaps in COVID-19 management and their consequences on physicians in terms of contracting infection and psychological well-being during the early phase of the pandemic. DESIGN, SETTINGS AND PARTICIPANTS: We conducted a nationwide cross-sectional online study to collect information from 420 intern doctors who were at their internship in government medical colleges from February to August 2020. METHODS: We performed univariate and bivariate analyses to assess COVID-19 management. We investigated the consequences of COVID-19 management on infection risk, experiencing stress, developing anxiety, depression and sleep disturbance using five sets of multivariable logistic regression analyses. RESULTS: Findings indicate a delay in first-case detection and identify people's tendency to hide COVID-19 symptoms as one of the possible causes of that delay. About 56% of the intern doctors experienced that patients were trying to hide COVID-19 symptoms in the earlier phase of the pandemic. More than half of the respondents did not get any training on COVID-19 from their working institutions. About 30% and 20% of the respondents did not use personal protective equipment (PPE) and masks while treating patients. Respondents who treated patients without PPE, masks, face shields and gloves were almost two times as likely to be infected by COVID-19. The odds of experiencing COVID-19-related stress was almost twofold among respondents who treated patients without wearing PPE and masks. Experiencing COVID-19-related stress was further associated with an increased risk of developing anxiety and depression that led to sleep disturbance. CONCLUSION: Ensuring the maximum utilization of limited resources during any public health crisis such as COVID-19 needs developing coping mechanisms by projecting future demand. Ensuring proper training and safety measures can reduce physical and psychological hazards among physicians.

Erratum to "Impact of delta variant and vaccination on SARS-CoV-2 secondary attack rate among household close contacts" [The Lancet Regional Health - Western Pacific 17 (2021) 100299].

[This corrects the article DOI: 10.1016/j.lanwpc.2021.100299.].

Exacerbation of Thrombotic Responses to Silver Nanoparticles in Hypertensive Mouse Model.

With advent of nanotechnology, silver nanoparticles, AgNPs owing majorly to their antibacterial properties, are used widely in food industry and biomedical applications implying human exposure by various routes including inhalation. Several reports have suggested AgNPs induced pathophysiological effects in a cardiovascular system. However, cardiovascular diseases such as hypertension may interfere with AgNPs-induced response, yet majority of them are understudied. The aim of this work was to evaluate the thrombotic complications in response to polyethylene glycol- (PEG-) coated AgNPs using an experimental hypertensive (HT) mouse model. Saline (control) or PEG-AgNPs (0.5 mg/kg) were intratracheally (i.t.) instilled four times, i.e., on days 7, 14, 21, and 28 post-angiotensin II-induced HT, or vehicle (saline) infusion. On day 29, various parameters were assessed including thrombosis in pial arterioles and venules, platelet aggregation in whole blood in vitro, plasma markers of coagulation, and fibrinolysis and systemic oxidative stress. Pulmonary exposure to PEG-AgNPs in HT mice induced an aggravation of in vivo thrombosis in pial arterioles and venules compared to normotensive (NT) mice exposed to PEG-AgNPs or HT mice given saline. The prothrombin time, activated partial thromboplastin time, and platelet aggregation in vitro were exacerbated after exposure to PEG-AgNPs in HT mice compared with either NT mice exposed to nanoparticles or HT mice exposed to saline. Elevated concentrations of fibrinogen, plasminogen activator inhibitor-1, and von Willebrand factor were seen after the exposure to PEG-AgNPs in HT mice compared with either PEG-AgNPs exposed NT mice or HT mice given with saline. Likewise, the plasma levels of superoxide dismutase and nitric oxide were augmented by PEG-AgNPs in HT mice compared with either NT mice exposed to nanoparticles or HT mice exposed to saline. Collectively, these results demonstrate that PEG-AgNPs can potentially exacerbate the in vivo and in vitro procoagulatory and oxidative stress effect in HT mice and suggest that population with hypertension are at higher risk of the toxicity of PEG-AgNPs.