Multibiofunctional Self-healing Adhesive Injectable Nanocomposite Polysaccharide Hydrogel.

Injectable hydrogels with good antimicrobial and antioxidant properties, self-healing characteristics, suitable mechanical properties, and therapeutic effects have great practical significance for developing treatments for pressing healthcare challenges. Herein, we have designed a novel, self-healing injectable hydrogel composite incorporating cross-linked biofunctional nanomaterials by mixing alginate aldehyde (Ox-Alg), quaternized chitosan (QCS), adipic acid dihydrazide (ADH), and copper oxide nanosheets surface functionalized with folic acid as the bioligand (F-CuO). Gelation was achieved under physiological conditions via the dynamic Schiff base cross-linking mechanism. The developed nanocomposite injectable hydrogel demonstrated the fast self-healing ability essential to bear deformation and outstanding antibacterial properties along with ROS scavenging ability. Furthermore, the optimized formulation of our F-CuO-embedded injectable hydrogel exhibited excellent cytocompatibility, blood compatibility, and in vitro wound healing performance. Taken together, the F-CuO nanosheet cross-linked injectable hydrogel composite presented herein offers a promising candidate biomaterial with multifunctional properties to develop solutions for addressing clinical challenges.

3D-Printed Silk Proteins for Bone Tissue Regeneration and Associated Immunomodulation.

Current bone repair methods have limitations, prompting the exploration of innovative approaches. Tissue engineering emerges as a promising solution, leveraging biomaterials to craft scaffolds replicating the natural bone environment, facilitating cell growth and differentiation. Among fabrication techniques, three-dimensional (3D) printing stands out for its ability to tailor intricate scaffolds. Silk proteins (SPs), known for their mechanical strength and biocompatibility, are an excellent choice for engineering 3D-printed bone tissue engineering (BTE) scaffolds. This article comprehensively reviews bone biology, 3D printing, and the unique attributes of SPs, specifically detailing criteria for scaffold fabrication such as composition, structure, mechanics, and cellular responses. It examines the structural, mechanical, and biological attributes of SPs, emphasizing their suitability for BTE. Recent studies on diverse 3D printing approaches using SPs-based for BTE are highlighted, alongside advancements in their 3D and four-dimensional (4D) printing and their role in osteo-immunomodulation. Future directions in the use of SPs for 3D printing in BTE are outlined.

Protective Role of Nanoceria-Infused Nanofibrous Scaffold toward Bone Tissue Regeneration with Senescent Cells.

The presence of oxidative stress in bone defects leads to delayed regeneration, especially in the aged population and patients receiving cancer treatment. This delay is attributed to the increased levels of reactive oxygen species (ROS) in these populations due to the accumulation of senescent cells. Tissue-engineered scaffolds are emerging as an alternative method to treat bone defects. In this study, we engineered tissue scaffolds tailored to modulate the adverse effects of oxidative stress and promote bone regeneration. We used polycaprolactone to fabricate nanofibrous mats by using electrospinning. We exploited the ROS-scavenging properties of cerium oxide nanoparticles to alleviate the high oxidative stress microenvironment caused by the presence of senescent cells. We characterized the nanofibers for their physical and mechanical properties and utilized an ionization-radiation-based model to induce senescence in bone cells. We demonstrate that the presence of ceria can modulate ROS levels, thereby reducing the level of senescence and promoting osteogenesis. Overall, this study demonstrates that ceria-infused nanofibrous scaffolds can be used for augmenting the osteogenic activity of senescent progenitor cells, which has important implications for engineering bone tissue scaffolds for patients with low regeneration capabilities.

Building psychological resilience in Armed Forces worldwide.

Psychological resilience among troops can be enhanced through relatively simple interventions. Globally, various Armed Forces have successfully implemented modules for building psychological resilience. Programs from different countries are listed, evaluated and their underpinnings explored. Recommendations for a variety of feasible and culturally acceptable interventions targeted at individuals, families, units, community and organizations in the Indian context have been made; ranging from mindfulness training to embedded combat psychologists. Interventions are likely to succeed if integrated within existing basic training and unit/career programs.

Smoking blunts sertraline response in depression: A prospective observational cohort study.

Background: Smoking is common in patients of depression and is known to affect response to antidepressants. This study was undertaken to evaluate the effect of smoking on the antidepressant effect of sertraline. Method: Patients with depression were divided into smoker and nonsmoker cohorts and followed up for 8 weeks. Serum sertraline levels were estimated using the high-performance liquid chromatography system. Response to treatment was evaluated with the Hamilton Depression Rating Scale (HAM-D). Results: Serum sertraline levels did not differ between smokers and nonsmokers at 4 and 8 weeks. Nonsmokers responded better to sertraline than smokers after 8 weeks. Adverse drug reaction profile did not vary between the two groups and was not impacted by serum sertraline levels. Nonsmokers showed a greater fall in the HAM-D score than smokers. Conclusion: This study found depression among smokers to be less responsive to sertraline. This was not explained by serum sertraline levels. Treatment of depression in smokers with sertraline might require higher doses and duration, with more frequent reviews.

Impact of cognitive behavioural intervention on caregiver burden in mothers of children diagnosed with cancer.

Background: Mothers of children diagnosed with cancer are found to have coping difficulties in various studies. Most of the studies were done on parents after their child has been newly diagnosed with malignancy, and very few studies were done on coping skills intervention. Hence, this study has been done to assess the impact of cognitive behavioural intervention on caregiver burden in mothers of children diagnosed with cancer. Methods: Twenty mothers coming to the outpatient department of paediatric oncology from 01 September 2018 to 30 April 2019 were enrolled for the study. The participants were administered General Health Questionnaire, Brief Coping Operation Preference Enquiry Scale, Zung Self-Rating Anxiety Scale, and Coping Inventory for Stressful Situations-21 (CISS-21) Scale. Sixteen sessions of cognitive behavioural intervention were given over 8 weeks to all the participants. Reassessment was done after 3 months by use of the above mentioned scales. Results: Participants' mean anxiety score was 49.40 (standard deviation [SD] ±8.89). They used adaptive (active coping and positive reframing) more than the maladaptive (denial and self-blame) coping strategies. Task- and emotion-focused coping mean score on CISS-21 revealed 19.25 (SD ±6.20) and 18.90 (SD ±5.76), respectively. Reassessment after cognitive behavioural intervention revealed statistically significant improvement in maladaptive coping styles, mean anxiety index score, avoidance, and emotion-focused coping. Conclusion: The study has revealed mild to moderate anxiety and the use of both adaptive and maladaptive coping strategies by participants. There is statistically significant improvement in anxiety, maladaptive coping strategies with cognitive behavioural intervention.

Longitudinal study of the course and outcome of first-episode psychosis.

Background: Study of first episode psychosis (FEP), an episode of psychotic nature, which manifests for the first time in an individual in the longitudinal continuum of his/her illness, has been a matter of research interest in recent years, as this may give more insight to the overall phenomenology and course of psychotic illnesses. Methods: A study was undertaken to evaluate course and outcome of first episode psychosis. A total of 100 consecutive inpatients were selected for the study. Informed consent was obtained. Structured Proforma was used for recording psychosocial profiles and relevant medical history. Brief Psychiatric Rating Scale (BPRS) was given to assess the severity of psychopathology; Positive and Negative Symptom Scale (PANSS) to assess the severity of psychosis; Becks Suicidal Ideation Scale (BSI) to assess the extent of suicidality and Global Assessment of Functioning (GAF) to assess global functioning of the individual. The assessment was done at baseline, at six months, and at one year. Results: First episode psychosis constituted around a tenth of the caseload. It commonly affected people in the third decade of life. There was an improvement in 92% of the cases over a year of study. Schizophrenia constituted the majority of first episode psychosis. The history of smoking was relatively higher in acute and transient psychotic disorders. Age inversely correlated with the severity of psychopathology. There was no difference in improvement in psychopathology over time in patients of schizophrenia and related disorder vis--vis other psychotic disorders. Conclusion: Our study did not find any significantly varied sociodemographic factors in the course and outcome of the illness. It also refuted the schism between various types of psychosis based on the current classificatory system. It draws our attention toward the unitary concept of psychosis and is a call to re-think our strategies in the management of psychosis.

Injectable Adhesive Hydrogels for Soft tissue Reconstruction: A Materials Chemistry Perspective.

Injectable bioadhesives offer several advantages over conventional staples and sutures in surgery to seal and close incisions or wounds. Despite the growing research in recent years few injectable bioadhesives are available for clinical use. This review summarizes the key chemical features that enable the development and improvements in the use of polymeric injectable hydrogels as bioadhesives or sealants, their design requirements, the gelation mechanism, synthesis routes, and the role of adhesion mechanisms and strategies in different biomedical applications. It is envisaged that developing a deep understanding of the underlying materials chemistry principles will enable researchers to effectively translate bioadhesive technologies into clinically-relevant products.

Surface Decoration of Redox-Modulating Nanoceria on 3D-Printed Tissue Scaffolds Promotes Stem Cell Osteogenesis and Attenuates Bacterial Colonization.

Oxidative stress at the bone defect site delays the bone regeneration process. Increased level of reactive oxygen species (ROS) is the primary cause of oxidative stress at the damaged site. Bone tissue scaffolds that scavenge ROS offer a potential and yet unexplored route for faster bone healing. Cerium oxide (ceria) is known for its redox-modulating behavior. Three-dimensional (3D)-printed porous scaffolds fabricated from degradable polymers provide a physical microenvironment but lack the bioactivity for tissue regeneration. In this work, porous poly(lactic acid) (PLA) scaffolds were prepared by 3D printing and modified with poly(ethylene imine) and citric acid to decorate with ceria nanoparticles. Scanning electron micrographs revealed a macroporous architecture decorated with ceria particles. The compressive modulus of 27 MPa makes them suitable for trabecular bone. The scaffolds supported human mesenchymal stem cell growth, confirming cytocompatibility. The ability to scavenge ROS confirmed that surface functionalization with ceria could reduce oxidative stress levels in the cells. Stem cell osteogenesis was enhanced after ceria decoration of the PLA scaffolds. Transcriptional profiling studied by sequencing revealed changes in the expression of genes associated with inflammation and cell-material interactions. The ceria-functionalized scaffolds show enhanced antibacterial activity against both Gram-negative and Gram-positive bacterial strains. These results demonstrate that surface decoration with nanoceria offers a viable route for enhancing the bioactivity of 3D-printed PLA scaffolds for bone tissue regeneration with ROS scavenging and antibacterial capability.

Strategies to Promote Vascularization in 3D Printed Tissue Scaffolds: Trends and Challenges.

Three-dimensional (3D) printing techniques for scaffold fabrication have shown promising advancements in recent years owing to the ability of the latest high-performance printers to mimic the native tissue down to submicron scales. Nevertheless, host integration and performance of scaffolds in vivo have been severely limited owing to the lack of robust strategies to promote vascularization in 3D printed scaffolds. As a result, researchers over the past decade have been exploring strategies that can promote vascularization in 3D printed scaffolds toward enhancing scaffold functionality and ensuring host integration. Various emerging strategies to enhance vascularization in 3D printed scaffolds are discussed. These approaches include simple strategies such as the enhancement of vascular in-growth from the host upon implantation by scaffold modifications to complex approaches wherein scaffolds are fabricated with their own vasculature that can be directly anastomosed or microsurgically connected to the host vasculature, thereby ensuring optimal integration. The key differences among the techniques, their pros and cons, and the future opportunities for utilizing each technique are highlighted here. The Review concludes with the current limitations and future directions that can help 3D printing emerge as an effective biofabrication technique to realize tissues with physiologically relevant vasculatures to ultimately accelerate clinical translation.

Fucoidan-Incorporated Composite Scaffold Stimulates Osteogenic Differentiation of Mesenchymal Stem Cells for Bone Tissue Engineering.

Globally, millions of bone graft procedures are being performed by clinicians annually to treat the rising prevalence of bone defects. Here, the study designed a fucoidan from Sargassum ilicifolium incorporated in an osteo-inductive scaffold comprising calcium crosslinked sodium alginate-nano hydroxyapatite-nano graphene oxide (Alg-HA-GO-F), which tends to serve as a bone graft substitute. The physiochemical characterization that includes FT-IR, XRD, and TGA confirms the structural integration between the materials. The SEM and AFM reveal highly suitable surface properties, such as porosity and nanoscale roughness. The incorporation of GO enhanced the mechanical strength of the Alg-HA-GO-F. The findings demonstrate the slower degradation and improved protein adsorption in the fucoidan-loaded scaffolds. The slow and sustained release of fucoidan in PBS for 120 h provides the developed system with an added advantage. The apatite formation ability of Alg-HA-GO-F in the SBF solution predicts the scaffold's osteointegration and bone-bonding capability. In vitro studies using C3H10T1/2 revealed a 1.5X times greater cell proliferation in the fucoidan-loaded scaffold than in the control. Further, the results determined the augmented alkaline phosphatase and mineralization activity. The physical, structural, and enriching osteogenic potential results of Alg-HA-GO-F indicate that it can be a potential bone graft substitute for orthopedic applications.

Recapitulating pathophysiology of skeletal muscle diseases in vitro using primary mouse myoblasts on a nanofibrous platform.

Tissue engineering approaches are used to mimic the microenvironment of the skeletal muscle in vitro. However, the validation of a bioengineered muscle as a model to study diseases is inadequate. Here, we present polycaprolactone nanofibers as a robust platform that mimics cellular organization and recapitulates critical functions of the myotubes observed in vivo. We isolated myoblasts from mice following a simplified protocol and cultured them on aligned nanofibers. Myotubes grown on aligned nanofibers maintained alignment for 14 days and exhibited a time-dependent increase in levels of p-AKT upon insulin stimulation. Treatment with matrix-assisted integrin inhibitor led to reduction in p-AKT levels, underscoring the critical role of environment on the biological processes. We demonstrate the suitability of myotubes grown on nanofibrous platform to study corticosteroid-induced muscle degeneration. This study, thus, demonstrates that aligned nanofibers retain myotubes in culture for longer duration and recapitulate the functions of skeletal muscle under pathophysiological conditions.

Acceptability and effectiveness of a poetic narrative video facilitated large classroom teaching in psychiatry.

BACKGROUND: Lecture based large classroom teaching is limited in scope of learning by being primarily. Teacher focussed, directive and monotonous with students often being passive participants. In psychiatry, problem is further compounded because of stigma around the subject and lack of summative assessment. Narratives and poems have been used in education to facilitate teaching. METHODS: 50 randomly selected medical undergraduate students were subjected to short poetic narrative video facilitated large classroom interactive lecture, while 50 other students were imparted traditional classroom lecture. Acceptability and effectiveness of this teaching learning modality was done with a questionnaire and multiple-choice questions on the given topic post the lecture. RESULT: Around 90 percent of the student found the modified classroom teaching to be acceptable. It was equally effective as traditional classroom teaching. Student and faculty reflected on the whole experience as innovative, immersive and appealing to empathy. CONCLUSION: Poetic narrative facilitated classroom teaching is an acceptable and equally effective modality of large classroom teaching.

Systematic review of predictive mathematical models of COVID-19 epidemic.

BACKGROUND: Various mathematical models were published to predict the epidemiological consequences of the COVID-19 pandemic. This systematic review has studied the initial epidemiological models. METHODS: Articles published from January to June 2020 were extracted from databases using search strings and those peer-reviewed with full text in English were included in the study. They were analysed as to whether they made definite predictions in terms of time and numbers, or contained only mathematical assumptions and open-ended predictions. Factors such as early vs. late prediction models, long-term vs. curve-fitting models and comparisons based on modelling techniques were analysed in detail. RESULTS: Among 56,922 hits in 05 databases, screening yielded 434 abstracts, of which 72 articles were included. Predictive models comprised over 70% (51/72) of the articles, with susceptible, exposed, infectious and recovered (SEIR) being the commonest type (mean duration of prediction being 3 months). Common predictions were regarding cumulative cases (44/72, 61.1%), time to reach total numbers (41/72, 56.9%), peak numbers (22/72, 30.5%), time to peak (24/72, 33.3%), hospital utilisation (7/72, 9.7%) and effect of lockdown and NPIs (50/72, 69.4%). The commonest countries for which models were predicted were China followed by USA, South Korea, Japan and India. Models were published by various professionals including Engineers (12.5%), Mathematicians (9.7%), Epidemiologists (11.1%) and Physicians (9.7%) with a third (32.9%) being the result of collaborative efforts between two or more professions. CONCLUSION: There was a wide diversity in the type of models, duration of prediction and the variable that they predicted, with SEIR model being the commonest type.

COVISHIELD (AZD1222) VaccINe effectiveness among healthcare and frontline Workers of INdian Armed Forces: Interim results of VIN-WIN cohort study.

BACKGROUND: On 16 Jan 2021, India launched its immunization program against COVID-19. Among the first recipients were 1.59 million Health Care Workers (HCWs) and Frontline Workers (FLWs) of the Indian Armed Forces, who were administered COVISHIELD (Astra Zeneca). We present an interim analysis of vaccine effectiveness (VE) estimates till 30 May 2021. METHODS: The VIN-WIN cohort study was carried out on anonymized data of HCWs and FLWs of Indian Armed Forces. The existing surveillance system, enhanced for COVID-19 monitoring, was sourced for data. The cohort transitioned from Unvaccinated (UV) to Partially Vaccinated (PV) to Fully Vaccinated (FV), serving as its own internal comparison. Outcomes studied in the three groups were breakthrough infections and COVID related deaths. Incidence Rate Ratio (IRR) was used to compare outcomes among the three groups to estimate VE. RESULTS: Data of 1,595,630 individuals (mean age 27.6 years; 99% male) over 135 days was analysed. Till 30 May 21, 95.4% and 82.2% were partially and fully vaccinated. The UV, PV and FV compartments comprised 106.6, 46.7 and 58.7 million person-days respectively. The number of breakthrough cases in the UV, PV and FV groups were 10061, 1159 and 2512; while the deaths were 37, 16 and 7 respectively. Corrected VE was 91.8-94.9% against infections. CONCLUSION: Interim results of the VIN-WIN cohort study of 1.59 million HCWs and FLWs of Indian Armed Forces showed a ∼93% reduction in COVID-19 breakthrough infections with COVISHIELD vaccination.

Polymers and Composites Derived from Castor Oil as Sustainable Materials and Degradable Biomaterials: Current Status and Emerging Trends.

Recent years have seen rapid growth in utilizing vegetable oils to derive a wide variety of polymers to replace petroleum-based polymers for minimizing environmental impact. Nonedible castor oil (CO) can be extracted from castor plants that grow easily, even in an arid land. CO is a promising source for developing several polymers such as polyurethanes, polyesters, polyamides, and epoxy-polymers. Several synthesis routes have been developed, and distinct properties of polymers have been studied for industrial applications. Furthermore, fillers and fibers, including nanomaterials, have been incorporated in these polymers for enhancing their physical, thermal, and mechanical properties. This review highlights the development of CO-based polymers and their composites with attractive properties for industrial and biomedical applications. Recent advancements in CO-based polymers and their composites are presented along with a discussion on future opportunities for further developments in diverse applications.

Coronavirus disease 2019 in India: Post-lockdown scenarios and provisioning for health care.

BACKGROUND: With the rise of Coronavirus disease 2019 (COVID-19) cases in India, lockdown was imposed from March 25, 2020. We studied post-lockdown scenarios and evaluated health-care constraints. Our aim was to identify the scenarios in which health-care availability would not be overwhelmed. METHODS: A modified compartmental SEIR stochastic model was used to calculate peak cases at various levels of effectiveness of prevention of transmission. Health-care constraints were evaluated using a Delphi study. We developed "q-metric" to evaluate the epidemic. Key constraints were matched against scenarios generated, and a monitoring mechanism was devised. RESULTS: Continuing lockdown ("q-metric" of >50) until mid-August was theoretically the most effective solution to end the epidemic. Lockdown might however be lifted earlier owing to various compulsions. The key constraints were identified as trained manpower and ventilators. It was estimated that shortfall of specialists to operate ventilators for COVID-19 intensive care units was approximately 40,000. This requires re-purposing of other specialists and short-term training to meet the surge. The shortage of ventilators is around 40,000-50,000. Procuring beyond those numbers would be infructuous owing to limits of training manpower. After lifting lockdown, the aim should be to contain the epidemic within the availability of key constraints. Our model suggests that this can be achieved by community containment and other non-pharmacological interventions at a "q-metric" of 19. An algorithm using "q-metric" was developed to monitor the epidemic. CONCLUSION: Various post-lockdown scenarios were simulated. Trained manpower and ventilators were identified as key health-care constraints. Partial community containment measures will require to be continued after the current lockdown is lifted.

Healthcare impact of COVID-19 epidemic in India: A stochastic mathematical model.

BACKGROUND: In India, the SARS-CoV-2 COVID-19 epidemic has grown to 1251 cases and 32 deaths as on 30 Mar 2020. The healthcare impact of the epidemic in India was studied using a stochastic mathematical model. METHODS: A compartmental SEIR model was developed, in which the flow of individuals through compartments is modeled using a set of differential equations. Different scenarios were modeled with 1000 runs of Monte Carlo simulation each using MATLAB. Hospitalization, intensive care unit (ICU) requirements, and deaths were modeled on SimVoi software. The impact of nonpharmacological interventions (NPIs) including social distancing and lockdown on checking the epidemic was estimated. RESULTS: Uninterrupted epidemic in India would have resulted in more than 364 million cases and 1.56 million deaths with peak by mid-July. As per the model, at current growth rate of 1.15, India is likely to reach approximately 3 million cases by 25 May, implying 125,455 (±18,034) hospitalizations, 26,130 (±3298) ICU admissions, and 13,447 (±1819) deaths. This would overwhelm India's healthcare system. The model shows that with immediate institution of NPIs, the epidemic might still be checked by mid-April 2020. It would then result in 241,974 (±33,735) total infections, 10,214 (±1649) hospitalizations, 2121 (±334) ICU admissions, and 1081 (±169) deaths. CONCLUSION: At the current growth rate of epidemic, India's healthcare resources will be overwhelmed by the end of May. With the immediate institution of NPIs, total cases, hospitalizations, ICU requirements, and deaths can be reduced by almost 90%.

Sirtuin 6 mediated stem cell cardiomyogenesis on protein coated nanofibrous scaffolds.

The cellular niche provides combination of biomolecular and biophysical cues to control stem cell fate. Three-dimensional (3D) aligned nanofibrous scaffolds can effectively augment stem cell cardiomyogenesis. This work aims to understand the role of biomolecular signals from extracellular matrix (ECM) proteins and leverage them to further promote cardiomyogenesis on nanofibrous scaffolds. Human mesenchymal stem cells (hMSCs) were cultured on 3D aligned polycaprolactone scaffolds coated with different ECM proteins. Among multiple coatings tested, collagen coated fibers were most effective in promoting cardiomyogenesis as determined from increased expression of cardiac biomarkers and intracellular calcium flux. At molecular level, enhanced differentiation on collagen coated fibers was associated with an increased level of sirtuin 6 (SIRT6). Depletion of SIRT6 using siRNA attenuated the differentiation process through activation of Wnt signaling pathway. This study, thus, demonstrates that protein coated scaffolds can augment cardiomyogenic differentiation of stem cells through a combination of topographical and biomolecular signals.

Multi-scale surface topography to minimize adherence and viability of nosocomial drug-resistant bacteria.

Toward minimizing bacterial colonization of surfaces, we present a one-step etching technique that renders aluminum alloys with micro- and nano-scale roughness. Such a multi-scale surface topography exhibited enhanced antibacterial effect against a wide range of pathogens. Multi-scale topography of commercially grade pure aluminum killed 97% of Escherichia coli and 28% of Staphylococcus aureus cells in comparison to 7% and 3%, respectively, on the smooth surfaces. Multi-scale topography on Al 5052 surface was shown to kill 94% of adhered E. coli cells. The microscale features on the etched Al 1200 alloy were not found to be significantly bactericidal, but shown to decrease the adherence of S. aureus cells by one-third. The fabrication method is easily scalable for industrial applications. Analysis of roughness parameters determined by atomic force microscopy revealed a set of significant parameters that can yield a highly bactericidal surface; thereby providing the design to make any surface bactericidal irrespective of the method of fabrication. The multi-scale roughness of Al 5052 alloy was also highly bactericidal to nosocomial isolates of E. coli, K. pneumoniae and P. aeruginosa. We envisage the potential application of engineered surfaces with multi-scale topography to minimize the spread of nosocomial infections.