Gelatin Methacryloyl (GelMA)-Based Biomaterial Inks: Process Science for 3D/4D Printing and Current Status.

Tissue engineering for injured tissue replacement and regeneration has been a subject of investigation over the last 30 years, and there has been considerable interest in using additive manufacturing to achieve these goals. Despite such efforts, many key questions remain unanswered, particularly in the area of biomaterial selection for these applications as well as quantitative understanding of the process science. The strategic utilization of biological macromolecules provides a versatile approach to meet diverse requirements in 3D printing, such as printability, buildability, and biocompatibility. These molecules play a pivotal role in both physical and chemical cross-linking processes throughout the biofabrication, contributing significantly to the overall success of the 3D printing process. Among the several bioprintable materials, gelatin methacryloyl (GelMA) has been widely utilized for diverse tissue engineering applications, with some degree of success. In this context, this review will discuss the key bioengineering approaches to identify the gelation and cross-linking strategies that are appropriate to control the rheology, printability, and buildability of biomaterial inks. This review will focus on the GelMA as the structural (scaffold) biomaterial for different tissues and as a potential carrier vehicle for the transport of living cells as well as their maintenance and viability in the physiological system. Recognizing the importance of printability toward shape fidelity and biophysical properties, a major focus in this review has been to discuss the qualitative and quantitative impact of the key factors, including microrheological, viscoelastic, gelation, shear thinning properties of biomaterial inks, and printing parameters, in particular, reference to 3D extrusion printing of GelMA-based biomaterial inks. Specifically, we emphasize the different possibilities to regulate mechanical, swelling, biodegradation, and cellular functionalities of GelMA-based bio(material) inks, by hybridization techniques, including different synthetic and natural biopolymers, inorganic nanofillers, and microcarriers. At the close, the potential possibility of the integration of experimental data sets and artificial intelligence/machine learning approaches is emphasized to predict the printability, shape fidelity, or biophysical properties of GelMA bio(material) inks for clinically relevant tissues.

Evolution of the atomic and electronic structures of CuO clusters: a comprehensive study using the DFT approach.

One of the most fundamental aspects of cluster science is to understand the structural evolution at the atomic scale. In this connection, here we report a comprehensive study of the atomic and electronic structures of (CuO)n clusters for n = 1 to 12 using DFT-based formalisms. Both the plane wave-based pseudo-potential approach and LCAO-MO-based method have been employed to obtain the ground state geometries of neutral, cation and anion copper oxide clusters. The results reveal that neutral copper oxide clusters favor a planar ring structure up to heptamer and from octamer onwards they adopt a three-dimensional motif with (CuO)9 and (CuO)12 forming a barrel-shaped layered structure. Detailed electronic structure analysis reveals that the transition of the atomic structure from 2D to 3D is guided by the energy balance of the Cu-O (d-p) and Cu-Cu (d-d) bonds. The removal of one electron from the cluster (cation) results in slightly stretched bonds while the addition of one electron (anion) showed compression in the overall geometries. The thermodynamic and electronic stability of these clusters has been analyzed by estimating their binding energy, ionization energy and electron affinity as a function of size. Remarkably, among these clusters, the octamer (CuO)8 and dodecamer (CuO)12 show higher binding energy and electron affinity (∼6.5 eV) with lower ionization energy (5.5-6.0 eV). This unique feature of the octamer and dodecamer indicates that they are very promising candidates for both oxidizing and reducing agents in different important chemical reactions.

Wavelength dependent photoionisation of ethanol clusters: generation of hydrogen like C5+ ions at terawatt laser intensity.

Photoionisation of ethanol clusters has been investigated at different laser wavelengths over the intensity range of ∼1012-1013 W cm-2. Under 266 nm ionisation, singly charged fragments and protonated cluster ions (up to (C2H5OH)9H+) were observed in the mass spectrum. Moreover, small ion signals corresponding to doubly charged carbon ions (C2+) were also observed. At longer laser wavelengths (i.e. 355, 532 and 1064 nm), the charge states of multiply charged ions of C and O were found to increase systematically and the maximum observed charge states were C5+ and O6+ at 1064 nm. Generation of C5+ ions (IE: 392 eV) is noteworthy as it requires removal of a core shell electron from a carbon atom. A comprehensive study has been carried out to appreciate the ionisation mechanism of such higher charge state formation in an ethanol cluster at terawatt laser intensity. A laser power dependency study suggests the role of multiphoton ionsation in creating initial charge centres within the cluster. Subsequently the ionised electrons produced upon multiphoton ionisation gain energy from the laser field and cause further ionisation via electron impact ionisation. Energisation of electrons and generation of multiply charged atomic ions were found to depend on the stability of clusters in the laser field which in turn is related to intermolecular interactions of ethanol clusters. Moreover, anionic fragment ions were observed in the ionisation of ethanol clusters at ∼1012 W cm-2 which also influences the ionisation dynamics of the cluster.

Mass spectrometric and charge density studies of organometallic clusters photoionized by gigawatt laser pulses.

Clusters on exposure to nanosecond laser pulses of gigawatt intensity exhibit a variety of photo-chemical processes such as fragmentation, intracluster reaction, ionization, Coulomb explosion, etc. Present article summarizes the experimental results obtained in our laboratory utilizing time-of-flight mass spectrometer which deal with one such aspect of cluster photochemistry related to generation of multiply charged atomic ions upon excessive ionization of cluster constituents (Coulomb explosion) at low intensity laser field (∼109 W/cm2 ). To understand the mechanism of laser-cluster interaction, laser as well as cluster parameters were varied. Mass spectrometric studies were carried out at different laser wavelength as well as varying the nature of cluster constituents, backup pressure, nozzle diameter, etc. In addition, charge density measurements were also preformed to get information about the total number of ions generated upon laser-cluster interaction as a function of laser wavelength. In case of pure molecular clusters, the charge state of atomic ions as well as charge density was observed to enhance with increasing laser wavelength, signifying efficient coupling of the cluster medium with nanosecond laser pulse at longer wavelength. While in case of clusters doped with species having comparatively lower ionization energy, the efficiency of laser-cluster interaction was less, in contrast to studies carried out using femtosecond lasers. Results obtained in the present work have been rationalized on the basis of proposed three-stage cluster ionization mechanism, that is, multiphoton ionization ignited-inverse Bremsstrahlung heating and electron ionization. © 2015 Wiley Periodicals, Inc. Mass Spec Rev. 36:188-212, 2017.

(TMT)n clusters as dilute debris-free tin source for generation of multiply charged tin ions-of relevance in extreme ultraviolet (EUV) lithography, under intense laser irradiation.

RATIONALE: Multiply charged tin ions ([Sn]8+ to [Sn]13+ ) are considered as ideal-emitters at extreme ultraviolet (EUV) wavelength ~ 13.5 nm, pertinent to advanced micro-electronic device fabrication. Solid tin targets have been widely explored for the generation of these ions, but debris generation has restricted their utilization. Tin-containing molecular clusters have, however, the potential to act as dilute and debris-free sources for the generation of tin ions, as investigated in the present study. METHODS: Efficient coupling of laser energy with clusters has been utilized for the generation of multiply charged tin ions. The ions generated have been characterized using time-of-flight mass spectrometry. By varying experimental parameters, the yield of multiply charged tin ions has been manipulated, for tetramethyltin (TMT) clusters. In addition, the energetic electrons and photons liberated upon laser-cluster interaction have been probed utilizing an in-house developed retarding field analyser. RESULTS: Interaction of tetramethyltin clusters with 1064 nm picosecond laser pulses of intensity ~ 1013 W/cm2 leads to the generation of multiply charged tin ions (up to [Sn]14+ ) and carbon ions (up to [C]4+ ). Efficient laser-cluster interaction is evident from the generation of multiply charged tin ions with ionization energy ~ 282 eV ([Sn]14+ ). By varying the experimental conditions, the distribution of multiply charged tin ions can be influenced to obtain significant relative ion yield of multiply charged tin ions from [Sn]8+ to [Sn]13+ . CONCLUSIONS: Tetramethyltin clusters have the potential to act as dilute and debris-free source for EUV lithographic applications, in contrast to bulk tin targets. The inherent properties of clusters, such as higher local density and the pulsed nature of the cluster source, are appropriate for EUV lithographic applications.

Efficient coupling of nanosecond laser pulses with the cluster medium: Generation of hydrogen-like [C](5+) atomic ions.

RATIONALE: Clusters exhibit diverse photochemical behavior as a function of laser parameters, i.e. wavelength, pulse duration and intensity. One such aspect of cluster photochemistry is the generation of energetic multiply charged atomic ions, upon efficient interaction of clusters with intense laser pulses. In the present work, mass spectrometric investigations have been carried out on clusters of tetrahydrofuran (THF, C4 H8 O) - a saturated cyclic ether - subjected to nanosecond laser pulse (spanning from UV to IR wavelength range) with the aim of shedding light on the complex mechanism of laser-cluster interactions, which is still ambiguous. METHODS: THF clusters, generated via supersonic expansion of room-temperature THF vapours seeded in argon, were subjected to gigawatt intensity laser pulses (355, 532 and 1064 nm) obtained from a nanosecond Nd:YAG laser. The ions generated upon laser-cluster interaction were characterized using a time-of-flight mass spectrometer. RESULTS: At 355 nm, THF clusters exhibit the usual multiphoton dissociation/ionization behavior while, at 532 nm, observation of multiply charged atomic ions of carbon (up to [C](4+) ) and oxygen (up to [O](3+) ) was ascribed to Coulomb explosion of THF clusters. For studies carried out at 1064 nm, multiply charged atomic ions of carbon up to [C](5+) having an ionization energy of ~392 eV were observed, at a laser intensity of 10(10) W/cm(2) . CONCLUSIONS: The observation of [C](5+) atomic ions signifies efficient coupling of the laser energy with the cluster medium, using a nanosecond laser pulse. The results have been rationalized on the basis of a three-stage cluster ionization mechanism, suggesting the crucial role of the threshold laser intensity for initiating ionization within the cluster and generation of optimum charge centers for efficient extraction of energy from the laser pulse.

Unveiling the patterns: exploring social and clinical characteristics of frequent mental health visits to the emergency department-a comprehensive systematic review.

BACKGROUND: Frequent presenters (FPs) are a group of individuals who visit the hospital emergency department (ED) frequently for urgent care. Many among the group present with the main diagnosis of mental health conditions. This group of individual tend to use ED resources disproportionally and significantly affects overall healthcare outcomes. No previous reviews have examined the profiles of FPs with mental health conditions. AIMS: This study aims to identify the key socio-demographic and clinical characteristics of patients who frequently present to ED with a mental health primary diagnosis by performing a comprehensive systematic review of the existing literature. METHOD: PRISMA guideline was used. PubMed, PsycINFO, Scopus and Web of Science (WOS) were searched in May 2023. A manual search on the reference list of included articles was conducted at the same time. Covidence was used to perform extraction and screening, which were completed independently by two authors. Inclusion and exclusion criteria were defined. RESULTS: The abstracts of 3341 non-duplicate articles were screened, with 40 full texts assessed for eligibility. 20 studies were included from 2004 to 2022 conducted in 6 countries with a total patient number of 25,688 (52% male, 48% female, mean age 40.7 years old). 27% were unemployed, 20% married, 41% homeless, and 17% had tertiary or above education. 44% had a history of substance abuse or alcohol dependence. The top 3 diagnoses are found to be anxiety disorders (44%), depressive disorders (39%) schizophrenia spectrum and other psychotic disorders (33%). CONCLUSION: On average, FPs are middle-aged and equally prevalent in both genders. Current data lacks representation for gender-diverse groups. They are significantly associated with high rates of unemployment, homelessness, lower than average education level, and being single. Anxiety disorder, depressive disorder, and schizophrenia spectrum disorders are the most common clinical diagnoses associated with the group.

Gut Microbiome Changes in Anorexia Nervosa: A Comprehensive Review.

Anorexia nervosa (AN) remains a challenging condition in psychiatric management and its pathogenesis is not yet fully understood. An imbalance in the gut microbiota composition may contribute to its pathophysiology. This review aims to explore the link between the human gut microbiota and AN (objective 1) or refeeding syndrome in AN (objective 2). The online databases MEDLINE and PsycINFO were searched for relevant studies. A total of 14 studies met the inclusion and exclusion criteria and only answered objective 1. A total of 476 AN patients, 554 healthy-weight (HC) controls, and 0 patients with other psychiatric disorders were included. Compared to HC, there were consistently reduced abundances of Faecalibacterium prausnitzii and Roseburia inulinivorans, and increased Methanobrevibacter smithii, in AN patients. Changes in alpha diversity were inconsistent, while beta diversity increased in four of six studies. Our model suggests that an imbalance in gut microbiota composition leads to reduced short-chain fatty acids, contributing to a proinflammatory state in AN, which is also common in other psychiatric comorbidities. Microbial changes may also contribute to the semistarvation state through endocrine changes and altered energy utilization.

Climate change and Indigenous mental health in Australia: In the aftermath of the defeat of the Voice referendum.

INTRODUCTION: This manuscript delves into the intricate connection between climate change and Indigenous mental health in Australia, with a focus on the aftermath of the defeat of the 'Voice' referendum. Climate change, recognized for its broad impact on mental health determinants, poses heightened risks to vulnerable communities, including Indigenous populations. The defeat of 'The Voice' referendum adds complexity, highlighting concerns about the lack of meaningful rights for the First Peoples of Australia. The bushfires further underscore ecological consequences, affecting Indigenous ecosystems and intensifying existing environmental challenges. Climate change exacerbates existing health challenges for Indigenous peoples, introducing new issues like ecological sorrow and anxiety. METHODOLOGY: The manuscript advocates for prioritized research in Indigenous communities to explore the link between climate change and mental health. It emphasizes interdisciplinary and collaborative research, giving voice to those directly affected by climate change. The lack of trust between Indigenous populations and authorities, along with the implications on self-determination, is crucial research focus. RESULTS: Renewable energy emerges as a potential solution deeply ingrained in Indigenous practices. The manuscript discusses challenges in achieving eco-friendly resettlement, emphasizing collaboration difficulties between the government and remote communities. The indigenous worldview, with its interconnectedness, is crucial for sustainable strategies. DISCUSSION AND FUTURE DIRECTIONS: Indigenous perspectives on planetary health are crucial, emphasizing the importance of Indigenous knowledge in shaping effective climate policies. The manuscript stresses dialogues between policymakers and Indigenous elders for formulating respectful land laws. It calls for global attention to the role of Indigenous peoples as biodiversity caretakers and urges recognition of their knowledge in climate change. Future directions include data collection for ecosystem protection, improving mental health outcomes post-climate events, and supporting impacted communities. Mental health care approaches in remote communities and practitioner training for climate-related issues are emphasized. The manuscript calls for increased funding for interdisciplinary research to understand the long-term impact of climate change on mental health, especially among vulnerable populations.

Advancing Peripheral Nerve Regeneration: 3D Bioprinting of GelMA-Based Cell-Laden Electroactive Bioinks for Nerve Conduits.

Peripheral nerve injuries often result in substantial impairment of the neurostimulatory organs. While the autograft is still largely used as the "gold standard" clinical treatment option, nerve guidance conduits (NGCs) are currently considered a promising approach for promoting peripheral nerve regeneration. While several attempts have been made to construct NGCs using various biomaterial combinations, a comprehensive exploration of the process science associated with three-dimensional (3D) extrusion printing of NGCs with clinically relevant sizes (length: 20 mm; diameter: 2-8 mm), while focusing on tunable buildability using electroactive biomaterial inks, remains unexplored. In addressing this gap, we present here the results of the viscoelastic properties of a range of a multifunctional gelatin methacrylate (GelMA)/poly(ethylene glycol) diacrylate (PEGDA)/carbon nanofiber (CNF)/gellan gum (GG) hydrogel bioink formulations and printability assessment using experiments and quantitative models. Our results clearly established the positive impact of the gellan gum on the enhancement of the rheological properties. Interestingly, the strategic incorporation of PEGDA as a secondary cross-linker led to a remarkable enhancement in the strength and modulus by 3 and 8-fold, respectively. Moreover, conductive CNF addition resulted in a 4-fold improvement in measured electrical conductivity. The use of four-component electroactive biomaterial ink allowed us to obtain high neural cell viability in 3D bioprinted constructs. While the conventionally cast scaffolds can support the differentiation of neuro-2a cells, the most important result has been the excellent cell viability of neural cells in 3D encapsulated structures. Taken together, our findings demonstrate the potential of 3D bioprinting and multimodal biophysical cues in developing functional yet critical-sized nerve conduits for peripheral nerve tissue regeneration.

Low-Concentration Gelatin Methacryloyl Hydrogel with Tunable 3D Extrusion Printability and Cytocompatibility: Exploring Quantitative Process Science and Biophysical Properties.

Three-dimensional (3D) bioprinting of hydrogels with a wide spectrum of compositions has been widely investigated. Despite such efforts, a comprehensive understanding of the correlation among the process science, buildability, and biophysical properties of the hydrogels for a targeted clinical application has not been developed in the scientific community. In particular, the quantitative analysis across the entire developmental path for 3D extrusion bioprinting of such scaffolds is not widely reported. In the present work, we addressed this gap by using widely investigated biomaterials, such as gelatin methacryloyl (GelMA), as a model system. Using extensive experiments and quantitative analysis, we analyzed how the individual components of methacrylated carboxymethyl cellulose (mCMC), needle-shaped nanohydroxyapatite (nHAp), and poly(ethylene glycol)diacrylate (PEGDA) with GelMA as baseline matrix of the multifunctional bioink can influence the biophysical properties, printability, and cellular functionality. The complex interplay among the biomaterial ink formulations, viscoelastic properties, and printability toward the large structure buildability (structurally stable cube scaffolds with 15 mm edge) has been explored. Intriguingly, the incorporation of PEGDA into the GelMA/mCMC matrix offered improved compressive modulus (∼40-fold), reduced swelling ratio (∼2-fold), and degradation rates (∼30-fold) compared to pristine GelMA. The correlation among microstructural pore architecture, biophysical properties, and cytocompatibility is also established for the biomaterial inks. These photopolymerizable bio(material)inks served as the platform for the growth and development of bone and cartilage matrix when human mesenchymal stem cells (hMSCs) are either seeded on two-dimensional (2D) substrates or encapsulated on 3D scaffolds. Taken together, this present study unequivocally establishes a significant step forward in the development of a broad spectrum of shape-fidelity compliant bioink for the 3D bioprinting of multifunctional scaffolds and emphasizes the need for invoking more quantitative analysis in establishing process-microstructure-property correlation.

Late onset psychosis in a case of 15q11.2 BP1-BP2 microdeletion (Burnside-Butler) syndrome: A case report and literature review.

Burnside-Butler syndrome is an inheritable genetic condition characterized by the partial deletion of specific genetic material located on chromosome 15q11. Individuals diagnosed with this particular medical condition display a variety of neuropsychiatric disorders, including psychosis, aggression, mood disorders, anxiety disorders, developmental disorders involving learning difficulties, language delays, autism spectrum disorders, and attention-deficit/hyperactivity disorder. The authors discuss the case of a 51-year-old Caucasian female diagnosed with Burnside-Butler syndrome at 8 years. The article highlights the importance of raising awareness regarding the complex nature and delayed onset of neuropsychiatric symptoms associated with this syndrome. It also emphasizes the need for comprehensive evaluation and multidisciplinary care for individuals affected by this uncommon condition.

A Case Report of a Patient with Soaring Clozapine Levels after Developing a Urinary Tract Infection.

Clozapine is an antipsychotic medicine used to treat mental illnesses that is resistant to therapy. It can induce dose-dependent adverse effects such as increased susceptibility to infections and hematological irregularities. In this case report, we present a 37-year-old woman with schizoaffective disorder who experienced clozapine side effects following a moderate urinary tract infection (UTI). Her serum clozapine levels and side effects were increased throughout her UTI but resolved once the UTI was managed conservatively. We reviewed clozapine's pharmacokinetic properties to understand why serum levels rose during infection. While we could not definitely explain the mechanism of elevation, we emphasize the importance of monitoring serum clozapine levels and keeping watchful for adverse effects, as well as heightened scrutiny, evaluation for recent infections, and regular monitoring of patients.

Comprehensive functional outcome analysis and importance of bone remodelling on personalized cranioplasty treatment using Poly(methyl methacrylate) bone flaps.

Cranioplasty involves the surgical reconstruction of cranial defects arising as a result of various factors, including decompressive craniectomy, cranial malformations, and brain injury due to road traffic accidents. Most of the modern decompressive craniectomies (DC) warrant a future cranioplasty surgery within 6-36 months. The conventional process of capturing the defect impression and polymethyl methacrylate (PMMA) flap fabrication results in a misfit or misalignment at the site of implantation. Equally, the intra-operative graft preparation is arduous and can result in a longer surgical time, which may compromise the functional and aesthetic outcomes. As part of a multicentric pilot clinical study, we recently conducted a cohort study on ten human subjects during 2019-2022, following the human ethics committee approvals from the participating institutes. In the current study, an important aspect of measuring the extent of bone remodelling during the time gap between decompressive craniectomy and cranioplasty was successfully evaluated. The sterilised PMMA bone flaps were implanted at the defect area during the cranioplasty surgery using titanium mini plates and screws. The mean surgery time was 90 ± 20 min, comparable to the other clinical studies on cranioplasty. No signs of intra-operative and post-operative complications, such as cerebrospinal fluid leakage, hematoma, or local and systemic infection, were clinically recorded. Importantly, aesthetic outcomes were excellent for all the patients, except in a few clinical cases, wherein the PMMA bone flap was to be carefully customized due to the remodelling of the native skull bone. The extent of physiological remodelling was evaluated by superimposing the pre-operative and post-operative CT scan data after converting the defect morphology into a 3D model. This study further establishes the safety and efficacy of a technologically better approach to fabricate patient-specific acrylic bone flaps with improved surgical outcomes. More importantly, the study outcome further demonstrates the strategy to address bone remodelling during the patient-specific implant design.

Complex neuropsychiatric presentation of 17q12 duplication syndrome: A case report.

The chromosomal band 17q12 is characterized by a high density of genes and is bordered by segmental duplications, the structural arrangement of which increases the susceptibility of the region to deletions and duplications. Duplication of 17q12 is a rare genetic condition associated with variable characteristics from clinically asymptomatic to intellectual disabilities, seizures, and behavioral problems. The variability in phenotype is primarily due to variable expressivity and incomplete penetrance. Diagnosis is mostly established by chromosomal microarray. Treatment involves a multidisciplinary approach. We present a case of a 43-year-old female who initially presented with hyperphagia and was eventually diagnosed with bulimia nervosa, anxiety, mood disorder, and personality disorder. Additional research is required to better understand the impact of 17q12 duplication syndrome on the development of bulimia nervosa since its pathogenesis has not been adequately described in the current literature.

Carbon sequestration and credit potential of gamhar (Gmelina arborea Roxb.) based agroforestry system for zero carbon emission of India.

The agroforestry system is the best option to achieve the net zero carbon emissions target for India. Keeping this view, carbon sequestration and credit potential of gamhar based agroforestry system has been assessed. The experiment was carried out in randomized block design in seven different treatments with five replications. Gamhar tree biomass accumulation was higher in gamhar based agroforestry system compared to sole gamhar. Among different tree components, stem contributed a maximum to total gamhar tree biomass followed by roots, leaves and branches. The average contributions of stems, roots, leaves and branches in total tree biomass in two annual cycles (2016-17 and 2017-18) varied between 50 and 60, 19.8 and 20, 19.2 and 20, and 10.7 and 12.7 percent, respectively. In case of crops, above ground, below ground and total biomass was significantly higher in sole intercrops than gamhar based agroforestry system. Total (Tree + interrops + Soil) carbon stock, carbon sequestration, carbon credit and carbon price were significantly affected by treatments, and was maximum in Sole Greengram-Mustard. Net carbon emission was also recorded lowest in Sole Greengram-Mustard for which the values were 811.55% and 725.24% and 760.69% lower than Sole Gamhar in 2016-17, 2017-18 and in pooled data, respectively.