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The microspheres are also called as micro-particles. Microspheres are characteristically spherical & free flowing powders having particle size ranging from 1-1000μm consisting of proteins or synthetic polymers. Microsphere can be manufactured by various type of material such as glass, polymers, and ceramic microspheres Microspheres are used in drug delivery systems to overcome some of the problems of conventional therapy and enhance the therapeutic efficacy of a given drug they are designed. These delivery systems offer numerous advantages compared to conventional dosage forms, which include improved efficacy, reduced toxicity, improved patient compliance and convenience. At the target tissue the drug should deliver in an optimal amount in the right period of time with the minimum side effect & maximum therapeutic effect, to get the desired effect. The microspheres received much attention not only for the prolonged release or controlled drug delivery to improve bioavailability, stability and action at the specific site to predetermined rate but also for targeting of the anticancer drugs to the tumour. Microspheres are various types like Bioadhesive microspheres, Magnetic microspheres, Floating microspheres, radioactive microspheres, Polymeric microspheres, Biodegradable polymeric microspheres, Synthetic polymeric microspheres. The microsphere are spherical microparticles & are used where predictable & consistent particle surface area is important. The microspheres has the drug located centrally within the particle where it is encased within the unique polymeric membrane. This review focuses on types, materials used, drawbacks, advantage & disadvantage.

Background: During the colonoscopy, colon tortuosity is a vital factor to complete the procedure successfully. Endoscopy can be difficult in cases with acute angle bending of adjacent colon segments. Aim: To assess the relationship of descending sigmoid colon flexure to vital anatomical points on CT in adult subjects. Methods: 114 adult subjects with CT examination of the abdominopelvic region were retrospectively analyzed. In 114 subjects, the angle between proximal sigmoid and descending colon was evaluated in degrees along with descending-sigmoid flexure position concerning the anterior aspect of the 5th lumbar vertebra, the median plane, and left anterior superior iliac spine. Results: Descending sigmoid flexure was seen in all 114 subjects. the LV-DSF was significantly higher in male subjects, with a distance of 123.7±23.1mm compared to female subjects where it was 115.6±21.2. This was statistically significant with p

Background Coronavirus disease (COVID–19) has resulted in the death of more than 3.5 million people worldwide. While COVID–19 mostly affects the lungs, different comorbidities can have an impact on its outcomes. We performed an overview of reviews to assess the effect of Chronic Kidney Disease (CKD) on contracting COVID–19, hospitalization, mortality, and disease severity. Methods We searched published and preprint databases. We updated the reviews by searching for primary studies published after August 2020, and prioritized reviews that are most updated and of higher quality using the AMSTAR tool. Results We included 69 systematic reviews and 66 primary studies. Twenty-eight reviews reported on the prevalence of CKD among patients with COVID–19, which ranged from 0.4 to 49.0%. One systematic review showed an increased risk of hospitalization in patients with CKD and COVID–19 (RR = 1.63, 95% CI 1.03–2.58) (Moderate certainty). Primary studies also showed a statistically significant increase of hospitalization in such patients. Thirty-seven systematic reviews assessed mortality risk in patients with CKD and COVID–19. The pooled estimates from primary studies for mortality in patients with CKD and COVID–19 showed a HR of 1.48 (95% CI 1.33–1.65) (Moderate certainty), an OR of 1.77 (95% CI 1.54–2.02) (Moderate certainty) and a RR of 1.6 (95% CI 0.88–2.92) (Low certainty). Conclusions Our review highlights the impact of CKD on the poor outcomes of COVID–19, underscoring the importance of identifying strategies to prevent COVID–19 infection among patients with CKD. Graphical abstract Supplementary Information The online version contains supplementary material available at 10.1007/s40620-021-01206-8.

The effectiveness of high-flow nasal oxygenation (HFNO) in patients with hypercapnic respiratory failure (RF) remains controversial. The current study compared the effectiveness of HFNO in patients with hypercapnic RF with conventional oxygen therapy (COT).The primary objective was to compare changes in the partial pressure of carbon dioxide (PaCO2) between those receiving COT and HFNO. The secondary objectives were to compare changes in the partial pressure of oxygen (PaO2), oxygen saturation (SpO2), respiratory rate (RR), serum bicarbonate level, base excess, lactate level, and incidence of the need for non-invasive ventilation (NIV) and mechanical ventilation (MV).We recruited 30 patients with mild to moderate hypercapnic RF in the HFNO group, and data of 30 patients from historical controls, who matched the inclusion criteria, were obtained from medical records for comparison (COT group). The study was terminated after two hours, and patients were managed per the existing protocol after that. Arterial blood gas (ABG) analysis was repeated at the baseline, first, second, and third hours.In the COT group, the mean RR at the baseline, first, second, and third hours was 24.5 ± 2.61, 24.9 ± 3.03, 26.03 ± 3.4, and 22.90 ± 1.86, whereas, in the HFNO group, it was 25.93 ± 3.91, 23.00 ± 3.54, 22.50 ± 3.38, and 21.90 ± 3.57, respectively. The mean PaCO2 in the COT vs. HFNO groups was 54.45 ± 5.83 vs. 62.22 ± 9.15, 57.74 ± 6.05 vs. 58.65 ± 10.43, 60.79 ± 7.48 vs. 60.41 ± 11.24, and 55.23 ± 6.63 vs. 56.95 ± 10.31. The mean SpO2 in the COT group at these points of time was 94.50 ± 1.46, 95.4 ± 1.28, 96.10 ± 1.84, and 97.53 ± 2.05, whereas, in the HFNO group, it was 95.40 ± 2.55, 98.63 ± 1.43, 99.00 ± 1.66, and 99.50 ± 1.31, respectively. The patients who needed NIV after the study period were 50% and 36.67% in the COT and HFNO groups, respectively.There was no change in PaCO2 levels with HFNO, but there was a significant improvement in SpO2 and PaO2 levels and a decreased RR. Following the termination of the study protocol, more patients in the COT group needed NIV than those in the HFNO group.

Background: The art of endotracheal intubation has a long-chequered history being accepted as the gold standard of the airway. This study was done to compare LMA and COPA in spontaneously breathing anaesthetized patients for short surgical elective procedures. Objectives: To compare Cuffed Oropharyngeal Airway (COPA) with Laryngeal Mask Airway (LMA) in terms of Placement success rate, Requirement of airway interventions and Intraoperative and postoperative complications. Materials and Methods: A prospective Randomized Controlled clinical study was conducted among 60 patients undergoing elective surgical procedure under Department of Anaesthesia in Krishna Institute of Medical Sciences and Hospital, Karad. Randomization was done and patients were divided into two Groups- A and B. Chi-Square test was used for analysis. Results: Male preponderance was seen in the study. Mean age in group A & B were 34.86 ±10.64 & 35.53 ±11.36 years respectively. First time successful insertion rate was higher in LMA group (93.33%) than COPA group (83.33%). No manoeuvres were required for clear, unobstructed airway in group A while in 40% of patients of COPA group required manoeuvres for clear, unobstructed airway. Coughing & gagging were observed in both the groups. But no intraoperative major complications are observed. Conclusion: Considering technical aspects of airway management, LMA is better than COPA with respect to higher first-time success rate of LMA. Keywords: Laryngeal Mask airway, Randomized controlled trial, Endotracheal intubation, Airway management, Sore throat.

Environmental pollution can be minimized by using xylanase pretreatment of pulp before chemical bleaching. A. flavus ARC-12 and S. commune ARC-11 produced 234.26 and 1147.11 IU/ml of xylanase under solid-state fermentation that was used for biobleaching of ethanol-soda pulp of Eulaliopsis binata. The brightness of bleached ethanol-soda pulp of E. binata increased by 3.2 and 1.9% (ISO) with A. flavus ARC-12 and S. commune ARC-11 xylanase respectively compared chemical bleaching at the same chlorine dioxide charge. While the consumption of chlorine dioxide were mitigated by 2.98 and 3.82% with A. flavus ARC-12 and S. commune ARC-11 xylanase pretreatment respectively. Moreover, A. flavus ARC-12 and S. commune ARC-11 xylanase pretreatment reduced AOX generation by 23.80 and 19.04% respectively compared to chemical bleaching.

ImportanceCoronavirus disease 2019 (COVID-19) has been reported to cause worse outcomes in patients with underlying cardiovascular disease, especially in patients with acute cardiac injury, which is determined by elevated levels of high-sensitivity troponin. There is paucity of data on the impact of congestive heart failure (CHF) on outcomes in COVID-19 patients.ObjectiveTo evaluate the occurrence of acute cardiac injury and arrhythmias and to assess the impact of pre-existing CHF and hypertension (HTN) in COVID-19 patients.Data SourcesWe conducted a literature search of PubMed/Medline, EMBASE, and Google Scholar databases from 11/1/2019 till 06/07/2020. databases using following search terms or keywords: “(COVID) AND (Clinical); ((heart) OR (myocard*)) AND (COVID); (COVID) AND (Troponin); (Coronavirus) AND (Heart).”Study SelectionWe identified all relevant studies reporting cardiovascular comorbidities, cardiac biomarkers, disease severity, and survival in COVID-19 patients.Data Extraction and SynthesisWe followed preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines for abstracting data. Pooled data was meta-analyzed using random-effects model and between-study heterogeneity was calculated with Higgins I2 statistic.Main outcome and measuresTo assess the impact of HTN and CHF and to evaluate different cardiac biomarkers in COVID-19 patients based on their disease severity.ResultsWe collected pooled data on 5,967 COVID-19 patients from 20 individual studies. We found that both non-survivors and those with severe disease had an increased risk of acute cardiac injury and cardiac arrhythmias, our pooled relative risk (RR) was — 8.52 (95% CI 3.63– 19.98) (pConclusion and RelevanceCardiac involvement in COVID-19 infection appears to significantly adversely impact patient prognosis and survival. Pre-existence of CHF, and high cardiac biomarkers like NT-pro BNP and CK-MB levels in COVID-19 patients correlates with worse outcomes.

Background Hydroxyapatite (HA) [Ca5(PO4)3(OH)] is a naturally occurring calcium phosphate which makes up 60-70% of the dry weight of human bones. Nano-scale HA particles are increasingly being used as carriers for controlled and targeted delivery of bioactive agents like drugs, proteins, and nucleic acids due to their high porosity, negative charge, and biodegradability. Purpose Although much effort has been devoted to understanding the delivery kinetics and effects of the payloads in such carriers, a thorough understanding of the influence of the carriers themselves is lacking. Methods HA particles (300 µg/mL) were administered to primary human dermal fibroblasts (HDFs). The uptake and intracellular localization of the particles were determined by flow cytometry, confocal imaging, and transmission electron microscopy (TEM). Immunological assays and PCR were performed to determine the levels of pro-inflammatory cytokines and collagens in cell lysates and media supernatant. Results The current study explores the effects of poly-dispersed HA particles on primary HDFs as a model system. The majority of the particles were determined to range between 150 and 200 nm in diameter. Upon exposure to HA suspensions, primary HDFs internalized the particles by endocytosis within 6 hours of exposure, showing maximum uptake at 72 hours following which the particles were exocytosed by 168 hours. This correlated to reduced secretion of various pro-inflammatory and pro-collagenic cytokines. Biochemical analysis further revealed a reduction in Type I collagen expression and secretion. Conclusion HA particles have an immune-modulatory effect on dermal fibroblasts and reduce collagen production, which may impact the integrity of the extracellular matrix (ECM). This study demonstrates the need to consider the secondary effects of particulate carriers like HA, beyond basic cytotoxicity, in the specific tissue environment where the intended function is to be realized.

Protein-protein interactions featuring intricate binding epitopes remain challenging targets for synthetic inhibitors. Interactions of NEMO, a scaffolding protein central to NF-κB signaling, exemplify this challenge. Various regulators are known to interact with different coiled coil regions of NEMO, but the topological complexity of this protein has limited inhibitor design. We undertook a comprehensive effort to block the interaction between vFLIP, a Kaposi’s sarcoma herpesviral oncoprotein, and NEMO using small molecule screening and rational design. Our efforts reveal that a tertiary protein structure mimic of NEMO is necessary for potent inhibition. The rationally designed mimic engages vFLIP directly causing complex disruption, protein degradation and suppression of NF-κB signaling in primary effusion lymphoma (PEL). NEMO mimic treatment induces cell death and delays tumor growth in a PEL xenograft model. Our studies with this inhibitor reveal the critical nexus of signaling complex stability in the regulation of NF-κB by a viral oncoprotein., NF-κB signalling involves the scaffold protein NEMO, which can be bound by the oncoprotein vFLIP to promote cell survival and oncogenic transformation. Here the authors rationally engineer a tertiary protein mimic of NEMO to disrupt the vFLIP-NEMO interaction to induce cell death.

The use of nanodiamonds for biomedical and consumer applications is growing rapidly. As their use becomes more widespread, so too do concerns around their cytotoxicity. The cytotoxicity of nanodiamonds correlates with their cellular internalisation and circulation time in the body. Both internalisation and circulation time are influenced by the formation of a protein corona on the nanodiamond surface. However, a precise understanding of both how the corona forms and evolves and its influence on cytotoxicity is lacking. Here, we investigated protein corona formation and evolution in response to two classes of nanodiamonds, pristine and aminated, and two types of proteins, bovine serum albumin and fibronectin. Specifically, we found that a corona made of bovine serum albumin (BSA), which represents the most abundant protein in blood plasma, reduced nanodiamond agglomeration. Fibronectin (FN9-10), the second most abundant protein found in the plasma, exhibited a significantly higher nanodiamond binding affinity than BSA, irrespective of the nanodiamond surface charge. Finally, nanodiamonds with a BSA corona displayed less cytotoxicity towards nonphagocytic liver cells. However, regardless of the type of corona (FN9-10 or BSA), both classes of nanodiamonds induced substantial phagocytic cell death. Our results emphasise that a precise understanding of the corona composition is fundamental to determining the fate of nanoparticles in the body.

Mitochondrial dysfunction underscores aging and diseases. Mitophagy (mitochondria + autophagy) is a quality control pathway that preserves mitochondrial health by targeting damaged mitochondria for autophagic degradation. Hence, molecules or compounds that can augment mitophagy are therapeutic candidates to mitigate mitochondrial-related diseases. However, mitochondrial stress remains the most effective inducer of mitophagy. Thus, identification of mitophagy-inducing regimes that are clinically relevant is favorable. In this study, pomegranate extract (PE) supplementation is shown to stimulate mitophagy. PE activates transcription factor EB (TFEB) to upregulate the expression of autophagy and lysosomal genes for mitochondrial quality control under basal and stress conditions. Basally, PE alters mitochondrial morphology and promotes recruitment of autophagosomes to the mitochondria (mitophagosome formation). Upon onset of mitochondrial stress, PE further augments mitophagosome formation, and engages PINK1 and Parkin to the mitochondria to potentiate mitophagy. This cellular phenomenon of PE-induced mitophagy helps to negate superfluous mitochondrial reactive oxygen species (ROS) production and mitochondrial impairment. Overall, our study highlights the potential of PE supplementation as a physiological therapy to modulate TFEB activity to alleviate mitochondrial dysfunction in aging and mitochondrial-related diseases.

Hair contains about 80% keratins and 1–3% melanin packaged in melanosomes. Both of these are high-value and functional raw materials that have potential applications in wide-ranging fields. While keratin extraction has been widely refined, efficient methods of melanosome extraction are limited. The extraction of melanosomes requires complete removal of keratin, thus combining keratin extraction and melanosome isolation is logical. Herein, a successive process to harvest melanosomes after keratin extraction from human hair waste was developed. The yield of melanosomes was about 1.3% of the total hair mass. The structure of harvested melanosomes is well preserved based on surface morphology and interior ultrastructural observations using electron microscopy. The chemical structure, ultraviolet (UV)-filtering ability, and thermal stability of the melanosomes are examined to demonstrate preservation of native functions. Our strategy of combining melanosome isolation with keratin extraction is shown to be effective and significantly improves the total resource recovery efficiency from human hair waste. Effective harvesting of functional melanosomes following keratin extraction from human hair.

Graphical abstract, Highlights • Okara was upcycled into encapsulation materials using microwave assisted technique. • Okara and zein as excipient used as encapsulation substrate for micronutrients. • The formulation produced desirable sequential release of micronutrients in SGF and SIF., Colossal amounts of food waste are generated and discarded daily at the expense of financial resources and at a detriment to the environment. One such food waste, okara – a soybean by-product, is valorized in this study by upcycling it into nutritional extracts for micronutrients encapsulation. Micronutrient malnutrition, particularly in the developing world, is a major public health challenge. Herein, okara extracts were obtained through a low-cost extraction process and was subsequently developed as an encapsulant material for micronutrients β-carotene, and ferrous sulphate encapsulation, using zein as an excipient. Spray-drying, as a scalable technique, was employed to produce various formulations which were assessed for release profiles, shelf-life, β-carotene antioxidant activity and cell cytotoxicity. Finally, an optimized dual-micronutrient formulation displayed a sequential release with ferrous sulphate releasing in simulated gastric fluid, and β-carotene releasing predominantly in simulated intestinal fluid. This sequential release profile favors the absorption of both the micronutrients and could potentially enhance their bioavailability.

Human hair fibers are structurally organized as a cortex protected by an outer scaly sheath (cuticle). Developing methods to isolate these two compartments will help to elucidate their roles in hair biology and develop potential applications. Herein, we developed enzymatic methods for human hair cuticle cell harvesting or removal. After a single treatment with esperase for three days, cuticle cells were released from hair shafts and effectively harvested by a series of filtration, centrifugation and resuspension steps. Separately, combining L-cysteine and either esperase or savinase could remove the entire cuticle layer to obtain descaled hair fibers. The physical and chemical structures, and performance of the isolated cuticle cells and descaled hair samples were characterized using electron microscopy, FTIR, solid state 13C NMR, TGA and DSC. Results show that the harvested cuticle cells contain mainly β-sheets and random coil structures, while descaled hair samples contain more α-helical structures. Harvested cuticle cells have greater thermal stability than the descaled hair samples below 260 C. The enzymatic methods developed in this study are convenient and easily controlled. They are effective not just for cuticle cell harvesting but also for surface modification and structure disintegration of hair fibers. Agency for Science, Technology and Research (A*STAR) Accepted version This research was supported by the Agency for Science, Technology and Research (A*STAR) under its Acne and Sebaceous Gland Program & Wound Care Innovation for the Tropics IAF-PP (H17/01/a0/008 & H17/01/a0/0L9), the China Scholarship Council (Grant No. 201906790039 to N.Z.), and the National Natural Science Foundation of China (51673087).

Hair contains about 80% keratins and 1–3% melanin packaged in melanosomes. Both of these are high-value and functional raw materials that have potential applications in wide-ranging fields. While keratin extraction has been widely refined, efficient methods of melanosome extraction are limited. The extraction of melanosomes requires complete removal of keratin, thus combining keratin extraction and melanosome isolation is logical. Herein, a successive process to harvest melanosomes after keratin extraction from human hair waste was developed. The yield of melanosomes was about 1.3% of the total hair mass. The structure of harvested melanosomes is well preserved based on surface morphology and interior ultrastructural observations using electron microscopy. The chemical structure, ultraviolet (UV)-filtering ability, and thermal stability of the melanosomes are examined to demonstrate preservation of native functions. Our strategy of combining melanosome isolation with keratin extraction is shown to be effective and significantly improves the total resource recovery efficiency from human hair waste. Agency for Science, Technology and Research (A*STAR) Accepted version This research was supported by the Agency for Science, Technology and Research (A*STAR) under its Acne and Sebaceous Gland Program & Wound Care Innovation for the Tropics IAF-PP (Grant Nos. H17/01/a0/008 & H17/01/a0/0L9), the National Natural Science Foundation of China (Grant No. 51673087), and the China Scholarship Council (Grant No.201906790039 to N.Z.).

Pretreatment of wood or other raw material with white-rot fungi (WRF) prior to pulping is known as biopulping. Lignin and hemicelluloses are removed selectively during early growth of WRF that produces enriched cellulose, known as selective delignification. Biopulping is considered as environment-friendly and cost-effective approach for delignification of lignocellulosic raw materials. The delignification efficiency of WRF during biopulping is directly related to ligninolytic enzymes production that is influence by several factors such as fungal strain, nature of raw material, oxygen availability, moisture content, pH, temperature, source of nitrogen, presence of Mn++and Cu++ions. The WRF, especiallyCeriporiopsis subvermispora,Trametes versicolorandPhanerochaete chrysosporium, have been used dominantly for the purpose of biopulping. It is an energy saving process that also improves brightness of pulp and strength properties including tensile index, burst index and folding endurance of paper. Significant decrease in kappa number has also been attained by fungal pretreatment of raw materials. Biological pretreatment of raw material also reduces the requirement of pulping chemicals.

Precise, automatic and reliable position control of micro-objects such as single particles, biological cells or bio-organisms is critical for applications in biotechnology and tissue engineering. However, conventional acoustofluidic techniques generally lack reliability and automation capability thus are often incapable of building an efficient and automated system where the biological cells need to be precisely manipulated in three dimensions (3D). To overcome these limitations, we developed an acoustofluidic closed-loop control system which is combined with computer vision techniques and standing surface acoustic waves (SSAWs) to implement selective, automatic and precise position control of an object, such as a single cell or microparticle in a microfluidic chamber. Position of the object is in situ extracted from living images that are captured from a video camera. By utilizing the closed-loop control strategy, the object is precisely moved to the desired location in 3D patterns or along designed trajectories by manipulating the phase angle and power signal of the SSAWs. Controlling of breast cancer cells has been conducted to verify the principle and biocompatibility of the control system. This system could be employed to build an automatic system for cell analysis, cell isolation, self-assembling of materials into complex microstructures, or lab-on-chip and organ-on-chip applications. Ministry of Education (MOE) Nanyang Technological University The authors gratefully acknowledge the support of (i) Nanyang Technological University and the Ministry of Education of Singapore through a PhD Scholarship; (ii) the UK Engineering and Physical Sciences Research Council (EPSRC) grants EP/P018998/1; (iii) Special Interesting Group of Acoustofluidics funded by UK Fluids Network (EP/N032861/1).

Rice straw is valuable resource that has been used as substrate for cost effective production of xylanase under solid-state fermentation by a newly isolated white rot fungi, S. commune ARC-11. Out of eleven carbon sources tested, rice straw was found most effective for the induction of xylanase that produced 4288.3 IU/gds of xylanase by S. commune ARC-11. Maximum xylanase production (6721.9 IU/gds) was observed on 8th day of incubation at temperature (30 °C), initial pH (7.0) and initial moisture content (70.0%). The supplementation of ammonium sulphate (0.08% N, as available nitrogen) enhanced the xylanase production up to 8591.4 IU/gds. The xylanase production by S. commune ARC-11 was further improved by the addition of 0.10%, (w/v) of Tween-20 as surfactant. The maximum xylanase activities were found at pH 5.0 and temperature 55 °C with a longer stability (180 min) at temperature 45, 50 and 55 °C. This xylanase preparation was also evaluated for the pre-bleaching of ethanol-soda pulp from Eulaliopsis binata. An enzyme dosage of 10 IU/g of xylanase resulted maximum decrease in kappa number (14.51%) with a maximum improvement 2.9% in ISO brightness compared to control. Keywords: Schizophyllum commune, Xylanase, Pre-bleaching, Rice straw, Eulaliopsis binata

Nanotoxicology encompasses the study of the toxicity of nanoparticles (NPs) in order to better understand the adverse effects of NPs on human health and evaluate the health risks associated with the use of NPs. With the influx of large numbers of nanomaterials in many applications such as cosmetics, paints, and medicine, nanotechnology has been gaining immense attention in recent years. Titanium dioxide (TiO2) and Zinc oxide (ZnO) NPs are produced abundantly and are among the most ubiquitously used NPs in various consumer products, especially sunscreens. Penetration of these NPs through the intact skin barrier has been shown, albeit at low levels. Concerns over their increased penetration across the skin in cases of the compromised or altered skin barrier and the consequent physiological influences are real. However, understanding of nanoparticle-mediated toxicity is still limited. Therefore, the goal of this study is to assess the physiological effects of TiO2 and ZnO NPs interactions with primary human epidermal keratinocytes and dermal fibroblasts, with attention to accurate dosimetry measurements and particle solubility considerations. Since the current findings on NPs interaction with skin cells are mostly based on 2D monolayer cell culture and animal models, in this study, 3D human skin explants have also been used to better understand the effects of NPs in the skin tissue. Based on 2D monolayer studies, it was observed that both TiO2 and ZnO NPs were toxic to cells at higher concentration, inducing various cellular responses such as oxidative stress, apoptosis, inflammation, and autophagy. The cellular response was dependent on the dose and exposure period. TiO2 NPs induced lower cytotoxicity even at higher doses, whereas ZnO NPs caused acute cell death at a much lower dose. Comparing the cellular responses of two cell types, it was observed that both NPs were comparatively more toxic to keratinocytes than to fibroblasts. In keratinocytes, the onset of autophagy was observed at much lower/non-toxic doses. At higher/sub-toxic doses, both autophagy, and inflammation were induced as NPs mediated toxicity. This study, for the first time, shows that autophagy induction at higher doses of TiO2 NPs blocked p65 phosphorylation in keratinocytes, thereby blocking the inflammatory pathway. However, this phenomenon was not observed in keratinocytes exposed to ZnO NPs. In contrast to this, NPs induced autophagy was not observed in dermal fibroblasts. Furthermore, from the studies performed on human skin explants, it was observed that TiO2 and ZnO NPs did not cause any significant effects on skin physiology and wound healing. Although these NPs proved to be toxic on cells based on 2D monolayer culture, their significant effects on cells in 3D human skin explants were not observed. Both NPs were internalized by the keratinocytes at the wound edge, and notably, penetrated into the nuclei of the keratinocytes. The penetration and uptake of NPs were also dependent on the dose and exposure period. Although higher amounts of TiO2 NPs penetrated into the nuclei, they did not cause significant DNA damage to the keratinocytes. On the other hand, ZnO NPs caused DNA damage to the keratinocytes located at the wound edge and migrating tongue of the wound. In summary, this study revealed that lower doses of TiO2 and ZnO NPs induced autophagy in keratinocyte acts as a pro-survival mechanism and protects the cell against oxidative stress and inflammation. At higher doses, they caused toxic effects to the cells, however, they did not significantly affect skin physiology or wound healing. Doctor of Philosophy

Current methods for the assessment of nanoparticle safety that are based on 2D cell culture models and fluorescence-based assays show limited sensitivity and they lack biomimicry. Consequently, the health risks associated with the use of many nanoparticles have not yet been established. There is a need to develop in vitro models that mimic physiology more accurately and enable high throughput assessment. There is also a need to set up new assays that offer high sensitivity and are label-free. Here we developed ‘mini-liver’ models using scaffold-free bioprinting and used these models together with label-free nanoscale techniques for the assessment of toxicity of nanodiamond produced by laser-assisted technology. Results showed that NDs induced cytotoxicity in a concentration and exposure-time dependent manner. The loss of cell function was confirmed by increased cell stiffness, decreased cell membrane barrier integrity and reduced cells mobility. We further showed that NDs elevated the production of reactive oxygen species and reduced cell viability. Our approach that combined mini-liver models with label-free high-resolution techniques showed improved sensitivity in toxicity assessment. Notably, this approach allowed for label-free semi-high throughput measurements of nanoparticle-cell interactions, thus could be considered as a complementary approach to currently used methods.

Takotsubo cardiomyopathy (TCM), also known as broken heart syndrome or stress-induced cardiomyopathy, is a rare condition with an estimated incidence of 0.02% of all hospitalizations in United States and 2% of all acute coronary syndrome presentations. TCM predominately presents as a transient wall motion abnormality of the left ventricular apex due to emotional or physical stress. Cardiac rupture in the setting of TCM is an extremely rare phenomenon with limited published case reports. We present a case of a 75-year-old female who had cardiac rupture secondary to TCM and performed a literature review using Ovid MEDLINE for published cases showing this association. After the literature review, we found 20 cases showing this association, which are listed in a tabular fashion.

Spatial distribution of biological cells plays a key role in tissue engineering for reconstituting the cellular microenvironment, and recently, acoustofluidics are explored as a viable tool for controlling structures in tissue fabrication because of its good biocompatibility, low-power consumption, automation capability, nature of non-invasive, and non-contact. Herein, a reusable acoustofluidic device is developed using surface acoustic waves for manipulating microparticles/cells to form a 3D matrix pattern inside a scaffold-based hydrogel contained in a millimetric chamber. The 3D patterned and polymerized hydrogel construct can be easily and safely removed from the chamber using a proposed lifting technique, which prevent any physical damages or contaminations and promote the reusability of the chamber. The generated 3D patterns of microparticles and cells are numerically studied using a finite-element method, which is well validated by the experimental results. The proposed acoustofluidic device is a useful tool for in vitro engineering 3D scaffold-based artificial tissues for drug and toxicity testing and building organs-on-chip applications. Ministry of Education (MOE) Nanyang Technological University The authors gratefully acknowledge the support of 1) Nanyang Technological University and the Ministry of Education of Singapore through a Ph.D. Scholarship and AcRF Tier 1 research grant (RG 96/18); 2) the UK Engineering and Physical Sciences Research Council (EPSRC) grants (EP/P018998/1); and 3) Special Interesting Group of Acoustofluidics funded by UK Fluids Network (EP/N032861/1).