Comparative Evaluation of Microhardness and Polymerization Shrinkage in Residual Zirconia Reinforced Provisional Restorations: An In Vitro Study.

Aim The aim of this study is to evaluate and compare the microhardness and polymerization shrinkage of polymethyl methacrylate reinforced with residual zirconia. Materials and methods A total of 360 resin samples were fabricated, with dimensions of 12 mm × 12 mm × 3 mm and 12 mm × 8 mm × 6 mm. Zirconia dust (40% by weight) was added to 180 of these samples. The study included four groups: Group A (autopolymerizing acrylic resin), Group H (heat-polymerizing acrylic resin), Group ZA (autopolymerizing acrylic resin with zirconia dust), and Group ZH (heat-polymerizing acrylic resin with zirconia dust). Each group consisted of 90 samples, with 45 samples used for evaluating microhardness and 45 samples for assessing polymerization shrinkage. Results Group ZH exhibited the highest microhardness at 6.06 ± 0.31 GPa. It also recorded the lowest shrinkage values, measuring 52.11 ± 3.21 mm³. Tukey's honestly significant difference test revealed that microhardness was significantly higher in Group ZA (4.53 ± 0.29 GPa) compared to Group A (3.51 ± 0.25 GPa). However, Group H (5.42 ± 0.26 GPa) demonstrated greater hardness than Group ZA. Regarding shrinkage, the addition of zirconia dust resulted in reduced values, with Group ZA (73.93 ± 3.55 mm³) showing less shrinkage compared to Group A (91.9 ± 6.38 mm³). Similarly, Group ZH (52.11 ± 3.21 mm³) had lower shrinkage than Group H (66.71 ± 5.97 mm³). Group A exhibited the highest shrinkage among all the groups. Conclusion Within the limitations of this study, it can be concluded that there is an increase in hardness and a decrease in shrinkage values of the resin with the addition of zirconia dust in heat and autopolymerizing acrylic resin used for the fabrication of provisional restorations. Zirconia-incorporated heat-activated resin showed superior microhardness and decreased shrinkage values. Although the addition of residual zirconia to autopolymerized samples demonstrated better hardness, it was observed that pure heat-polymerized samples showed greater hardness. Reusing computer-aided design and computer-aided manufacturing powder waste can cut down on economic losses and aid in environmental sustainability.

Incidence of Coronary Artery Disease After Permanent Pacemaker Implantation: A Hospital-based Study from East India.

Bradyarrhythmias, characterized by heart rates of <60 bpm due to conduction issues, carry risks of sudden cardiac death and falls. Pacemaker implantation is a standard treatment, but the interplay between bradyarrhythmias, coronary artery disease (CAD), and patient attributes requires further exploration. This study was a retrospective hospital record-based study that analyzed data from 699 patients who underwent pacemaker implantation for symptomatic bradyarrhythmias between February 2019 and February 2022. Clinical parameters, coronary angiography (CAG) findings, ejection fraction, and indications for pacemaker implantation were documented. The relationship between CAD severity, specific bradyarrhythmias, and ejection fraction was explored. Statistical analysis included chi-squared tests and t tests. The mean age of the study population (n = 699) was 66.75 years (male:female ratio, 70:30), with 77.2% having type 2 diabetes and 61.6% being hypertensive. The majority of patients had minor or non-obstructive CAD (61.8%), followed by normal CAG findings (25.75%) and obstructive CAD (12.45%). Complete heart block (CHB) was the primary indication for pacemaker implantation (55.2%), followed by sick sinus syndrome (22.3%). The results did not show any association between ejection fraction and CAG findings. Patients who presented with CHB had a higher incidence of obstructive CAD, indicating greater severity. This study sheds light on the intricate interplay between severe bradyarrhythmias, CAD, and patient characteristics. Our analysis revealed no statistical significance between obstructive CAD and the need for a permanent pacemaker. This makes us question our practice of maintaining a low threshold for coronary angiography during pacemaker implantation. The observed low yield and anticoagulation protocol reassure us of the choice to delay this diagnostic intervention. These insights can guide tailored management strategies, enhancing clinical care approaches for patients with severe bradyarrhythmias necessitating pacemaker implantation.

Outcomes of the EMDataResource cryo-EM Ligand Modeling Challenge.

The EMDataResource Ligand Model Challenge aimed to assess the reliability and reproducibility of modeling ligands bound to protein and protein-nucleic acid complexes in cryogenic electron microscopy (cryo-EM) maps determined at near-atomic (1.9-2.5 Å) resolution. Three published maps were selected as targets: Escherichia coli beta-galactosidase with inhibitor, SARS-CoV-2 virus RNA-dependent RNA polymerase with covalently bound nucleotide analog and SARS-CoV-2 virus ion channel ORF3a with bound lipid. Sixty-one models were submitted from 17 independent research groups, each with supporting workflow details. The quality of submitted ligand models and surrounding atoms were analyzed by visual inspection and quantification of local map quality, model-to-map fit, geometry, energetics and contact scores. A composite rather than a single score was needed to assess macromolecule+ligand model quality. These observations lead us to recommend best practices for assessing cryo-EM structures of liganded macromolecules reported at near-atomic resolution.

Assessment of coping capacity of public health facilities with health emergency situations during an event of flood in Mumbai.

BACKGROUND: Floods had been a repeated phenomenon in India, causing considerable losses to properties, life and infrastructure, and public utilities. Floods are found to be a common natural disaster occurring not only in developing countries but also in developed nations. Hospital preparedness against disaster could help in the management of the surge of patients in an effective manner. This study aims to assess the capacity of public health facilities for coping up with health emergency situations during an event of flood in Mumbai. MATERIALS AND METHODS: A cross-sectional study was conducted among 38 public health facilities in Mumbai. A purposive sampling technique was used for the selection of the health facilities. Administrative staff, medical officers, and pharmacy in charges were included in the study. RESULTS: The study revealed that surge capacities in hospitals were adequate as they had additional beds for monsoon-related diseases for the preceding flood situation. There was a triage policy, and the staff were trained on the same. Procurement of drugs was easy because of a good networking system between hospitals. Due to this networking system, patients were also transferred to the nearest healthcare facility in a short span of time. CONCLUSION: The response during an event of a flood in the health facilities of Mumbai city was good as they have regular training sessions to be prepared for the emergency situations during monsoon as they have repeated exposure to floods.

E-classroom as a Blended Learning Tool: A Structural Equation Modelling Analysis Using Modified Technology Acceptance Model.

BACKGROUND: E-classrooms help teachers save time, keep classes organized, and improve communication with students. This study aims to assess Google Classroom's usefulness in enhancing medical students' knowledge and acceptance of new technology for in-depth learning. MATERIAL AND METHOD: This educational interventional study was carried out on 100 students in the 3rd year of the M.B.B.S., Part 1. After a briefing about Google Classroom and educational topics, enrolled students and faculty were allowed to discuss the topic for two months. Following this, the descriptive approach was utilized to describe the respondents' technology acceptance through the administration of the technology acceptance model (TAM) survey questionnaire. RESULTS: Students were actively involved in discussion, with a 67% response rate. Nearly 85% of students agreed that Google Classroom is a satisfactory way for in-depth knowledge acquisition. On factor analysis, it was observed that the goodness of fit was 0.985, suggesting that the model is acceptable. It was also found that perceived usefulness (PU) had a significant positive effect on motivation towards self-directed learning (SDL), and perceived ease of use (PEOU) had a positive effect on both behavioural intention and actual use. CONCLUSION: Google Classroom is a valuable tool for learning that can enhance active self-learning and increase behavioural intention and actual use. It should be incorporated into day-to-day teaching activities to overcome time constraints.

Chemical kinetics and thermodynamics of PPO activity, colour changes and microbial degradation during blanching of the sugarcane billets.

BACKGROUND: Sugarcane juice, which has a short shelf life, is a popular thirst-quenching and rejuvenating beverage worldwide. The limited shelf life is a result of changes in polyphenol oxidase (PPO) activity, total plate count (TPC) and color attributes (L*, a* and b*-values). We hypothesized that chemical kinetics and thermodynamics of blanched sugarcane cane juice causing alterations in PPO, TPC, and L, a* and b*-values will address the challenges of sugarcane juice preservation. RESULTS: Sugarcane billets were blanched at variable time-temperature combinations in the range 0-20 min and 70-90 °C. Reaction rates increased with increasing temperature; PPO activity, TPC and colour followed first-order kinetics. PPO activity had an activation energy (Ea) of 81 kJ mol-1. The half life (t½) dropped from 16.5 to 3.47 min and decimal reduction time (D-values) dropped from 54.83 to 11.52 min. Thus reactions were temperature-sensitive. Thermodynamic studies indicated an endothermic (positive enthalpy values, ΔH > 0; 78.10 kJ mol-1) and reversible process (negative entropy values ΔS < 0; -0.044 kJmol-1 K-1). Michaeli-Menten constant (Km) and maximum velocity (Vmax) of PPO activity were determined by adding variable lemon juice concentrations in sugarcane juice. As the Km values increased (from 5.53 to 15.81 mm) and Vmax values decreased (from 666.67 to 384.61 UmL-1), a Lineweaver-Burk plot suggested decreased PPO affinity of sugarcane juice. CONCLUSION: The results of the present study indicate that studies on chemical kinetics and thermodynamics (PPO, TPC and L, a* and b*-values) of blanched sugarcane cane juice shall mitigate challenges of sugarcane juice preservation. © 2024 Society of Chemical Industry.

Lower serum uric acid and impairment of right cerebral hemisphere structural brain networks are related to depressive symptoms in cerebral small vessel disease: A cross-sectional study.

Cerebral small vessel disease (SVD) may be associated with an increased risk of depressive symptoms. Serum uric acid (SUA), an antioxidant, may be involved in the occurrence and development of depressive symptoms, but the mechanism remains unknown. Moreover, the relationship between structural brain networks and SUA has not been explored. This study examined the relationship between SUA and depressive symptoms in patients with SVD using graph theory analysis. We recruited 208 SVD inpatients and collected fasting blood samples upon admission. Depressive symptoms were assessed using the 24-item Hamilton Depression Rating Scale (HAMD-24). Magnetic resonance imaging was used to evaluate SVD, and diffusion tensor images were used to analyze structural brain networks using graph theory. Patients with depressive symptoms (n = 34, 25.76%) compared to those without (334.53 vs 381.28 µmol/L, p = 0.017) had lower SUA levels. Graph theoretical analyses showed a positive association of SUA with betweenness centrality, nodal efficiency, and clustering coefficients and a negative correlation with the shortest path length in SVD with depressive symptoms group. HAMD scores were significantly associated with nodal network metrics in the right cerebral hemisphere. Our findings suggested that lower SUA levels are significantly associated with disrupted structural brain networks in the right cerebral hemisphere of patients with SVD who have depressive symptoms.

Small molecules that disrupt RAD54-BLM interaction hamper tumor proliferation in colon cancer chemoresistance models.

RAD54 and BLM helicase play pivotal roles during homologous recombination repair (HRR) to ensure genome maintenance. BLM amino acids (aa 181-212) interact with RAD54 and enhance its chromatin remodeling activity. Functionally, this interaction heightens HRR, leading to a decrease in residual DNA damage in colon cancer cells. This contributes to chemoresistance in colon cancer cells against cisplatin, camptothecin, and oxaliplatin, eventually promoting tumorigenesis in preclinical colon cancer mouse models. ChIP-Seq analysis and validation revealed increased BLM and RAD54 corecruitment on the MRP2 promoter in camptothecin-resistant colon cancer cells, leading to BLM-dependent enhancement of RAD54-mediated chromatin remodeling. We screened the Prestwick small-molecule library, with the intent to revert camptothecin- and oxaliplatin-induced chemoresistance by disrupting the RAD54-BLM interaction. Three FDA/European Medicines Agency-approved candidates were identified that could disrupt this interaction. These drugs bound to RAD54, altered its conformation, and abrogated RAD54-BLM-dependent chromatin remodeling on G5E4 and MRP2 arrays. Notably, the small molecules also reduced HRR efficiency in resistant lines, diminished anchorage-independent growth, and hampered the proliferation of tumors generated using camptothecin- and oxaliplatin-resistant colon cancer cells in both xenograft and syngeneic mouse models in BLM-dependent manner. Therefore, the 3 identified small molecules can serve as possible viable candidates for adjunct therapy in colon cancer treatment.

Outcomes of the EMDataResource Cryo-EM Ligand Modeling Challenge.

The EMDataResource Ligand Model Challenge aimed to assess the reliability and reproducibility of modeling ligands bound to protein and protein/nucleic-acid complexes in cryogenic electron microscopy (cryo-EM) maps determined at near-atomic (1.9-2.5 Å) resolution. Three published maps were selected as targets: E. coli beta-galactosidase with inhibitor, SARS-CoV-2 RNA-dependent RNA polymerase with covalently bound nucleotide analog, and SARS-CoV-2 ion channel ORF3a with bound lipid. Sixty-one models were submitted from 17 independent research groups, each with supporting workflow details. We found that (1) the quality of submitted ligand models and surrounding atoms varied, as judged by visual inspection and quantification of local map quality, model-to-map fit, geometry, energetics, and contact scores, and (2) a composite rather than a single score was needed to assess macromolecule+ligand model quality. These observations lead us to recommend best practices for assessing cryo-EM structures of liganded macromolecules reported at near-atomic resolution.

The role of perfusion, grey matter volume and behavioural phenotypes in the data-driven classification of cognitive syndromes.

BACKGROUND: The use of structural and perfusion brain imaging in combination with behavioural information in the prediction of cognitive syndromes using a data-driven approach remains to be explored. Here, we thus examined the contribution of brain structural and perfusion imaging and behavioural features to the existing classification of cognitive syndromes using a data-driven approach. METHODS: Study participants belonged to the community-based Biomarker and Cognition Cohort Study in Singapore who underwent neuropsychological assessments, structural-functional MRI and blood biomarkers. Participants had a diagnosis of cognitively normal (CN), subjective cognitive impairment (SCI), mild cognitive impairment (MCI) and dementia. Cross-sectional structural and cerebral perfusion imaging, behavioural scale data including mild behaviour impairment checklist, Pittsburgh Sleep Quality Index and Depression, Anxiety and Stress scale data were obtained. RESULTS: Three hundred seventy-three participants (mean age 60.7 years; 56% female sex) with complete data were included. Principal component analyses demonstrated that no single modality was informative for the classification of cognitive syndromes. However, multivariate glmnet analyses revealed a specific combination of frontal perfusion and temporo-frontal grey matter volume were key protective factors while the severity of mild behaviour impairment interest sub-domain and poor sleep quality were key at-risk factors contributing to the classification of CN, SCI, MCI and dementia (p < 0.0001). Moreover, the glmnet model showed best classification accuracy in differentiating between CN and MCI cognitive syndromes (AUC = 0.704; sensitivity = 0.698; specificity = 0.637). CONCLUSIONS: Brain structure, perfusion and behavioural features are important in the classification of cognitive syndromes and should be incorporated by clinicians and researchers. These findings illustrate the value of using multimodal data when examining syndrome severity and provide new insights into how cerebral perfusion and behavioural impairment influence classification of cognitive syndromes.

Mild Behavioral Impairment and Cerebrovascular Profiles Are Associated with Early Cognitive Impairment in a Community-Based Southeast Asian Cohort.

Background: Mild behavioral impairment (MBI) is one of the earliest observable changes when a person experiences cognitive decline and could be an early manifestation of underlying Alzheimer's disease neuropathology. Limited attention has been given to investigating the clinical applicability of behavioral biomarkers for detection of prodromal dementia. Objective: This study compared the prevalence of self-reported MBI and vascular risk factors in Southeast Asian adults to identify early indicators of cognitive impairment and dementia. Methods: This cohort study utilized baseline data from the Biomarkers and Cognition Study, Singapore (BIOCIS). 607 participants were recruited and classified into three groups: cognitively normal (CN), subjective cognitive decline (SCD), and mild cognitive impairment (MCI). Group comparisons of cognitive-behavioral, neuroimaging, and blood biomarkers data were applied using univariate analyses. Multivariate logistic regression analyses were conducted to investigate the association between cerebrovascular disease, vascular profiles, and cognitive impairment. Results: SCD had significantly higher depression scores and poorer quality of life (QOL) compared to CN. MCI had significantly higher depression scores; total MBI symptoms, MBI-interest, MBI-mood, and MBI-beliefs; poorer sleep quality; and poorer QOL compared to CN. Higher Staals scores, glucose levels, and systolic blood pressure were significantly associated with MCI classification. Fasting glucose levels were significantly correlated with depression, anxiety, MBI-social, and poorer sleep quality. Conclusions: The results reflect current research that behavioral changes are among the first symptoms noticeable to the person themselves as they begin to experience cognitive decline. Self-reported questionnaires may aid in early diagnoses of prodromal dementia. Behavioral changes and diabetes could be potential targets for preventative healthcare for dementia.

RIP-seq reveals RNAs that interact with RNA polymerase and primary sigma factors in bacteria.

Bacteria have evolved structured RNAs that can associate with RNA polymerase (RNAP). Two of them have been known so far-6S RNA and Ms1 RNA but it is unclear if any other types of RNAs binding to RNAP exist in bacteria. To identify all RNAs interacting with RNAP and the primary σ factors, we have established and performed native RIP-seq in Bacillus subtilis, Corynebacterium glutamicum, Streptomyces coelicolor, Mycobacterium smegmatis and the pathogenic Mycobacterium tuberculosis. Besides known 6S RNAs in B. subtilis and Ms1 in M. smegmatis, we detected MTS2823, a homologue of Ms1, on RNAP in M. tuberculosis. In C. glutamicum, we discovered novel types of structured RNAs that associate with RNAP. Furthermore, we identified other species-specific RNAs including full-length mRNAs, revealing a previously unknown landscape of RNAs interacting with the bacterial transcription machinery.

Antiviral fibrils of self-assembled peptides with tunable compositions.

The lasting threat of viral pandemics necessitates the development of tailorable first-response antivirals with specific but adaptive architectures for treatment of novel viral infections. Here, such an antiviral platform has been developed based on a mixture of hetero-peptides self-assembled into functionalized ß-sheets capable of specific multivalent binding to viral protein complexes. One domain of each hetero-peptide is designed to specifically bind to certain viral proteins, while another domain self-assembles into fibrils with epitope binding characteristics determined by the types of peptides and their molar fractions. The self-assembled fibrils maintain enhanced binding to viral protein complexes and retain high resilience to viral mutations. This method is experimentally and computationally tested using short peptides that specifically bind to Spike proteins of SARS-CoV-2. This platform is efficacious, inexpensive, and stable with excellent tolerability.

Longitudinal single cell atlas identifies complex temporal relationship between type I interferon response and COVID-19 severity.

Due to the paucity of longitudinal molecular studies of COVID-19, particularly those covering the early stages of infection (Days 1-8 symptom onset), our understanding of host response over the disease course is limited. We perform longitudinal single cell RNA-seq on 286 blood samples from 108 age- and sex-matched COVID-19 patients, including 73 with early samples. We examine discrete cell subtypes and continuous cell states longitudinally, and we identify upregulation of type I IFN-stimulated genes (ISGs) as the predominant early signature of subsequent worsening of symptoms, which we validate in an independent cohort and corroborate by plasma markers. However, ISG expression is dynamic in progressors, spiking early and then rapidly receding to the level of severity-matched non-progressors. In contrast, cross-sectional analysis shows that ISG expression is deficient and IFN suppressors such as SOCS3 are upregulated in severe and critical COVID-19. We validate the latter in four independent cohorts, and SOCS3 inhibition reduces SARS-CoV-2 replication in vitro. In summary, we identify complexity in type I IFN response to COVID-19, as well as a potential avenue for host-directed therapy.

Alcoholic vs. non-alcoholic chronic pancreatitis: surgeons' perspective from a tertiary centre in india / Perspectiva dos cirurgiões sobre pancreatite crônica alcoólica vs. não-alcoólica de um centro terciário na índia

ABSTRACT Background: Although alcohol is the most common cause for chronic pancreatitis worldwide, idiopathic type is prevalent in India. Natural history and disease progression are different between these two groups. There is paucity of data comparing surgical outcome and quality of life in these patients. Aim: To evaluate clinical features, surgical outcome and quality of life between these two groups of patients. Method: All patients with chronic pancreatitis who underwent surgery were prospectively reviewed. Results: From 98 patients, 42 were alcoholic. Number of male and the mean age at the time of operation was significantly more in alcoholic patients. Smoking, preoperative hospital admission rate and the prevalence of local complications like inflammatory pancreatic head mass, biliary stricture and left sided portal hypertension were distinctly more common in alcoholic group. Frey procedure was required more commonly in alcoholic group. Mean postoperative hospital stay and overall postoperative complication rate were comparable between the two groups. Over a median follow up of 18 months there was significant improvement in quality of life and pain score in both the groups. Improvement of physical functioning score at follow-up was significantly more in alcoholic group but the requirement for analgesic medications were significantly more in alcoholic group. However, appetite loss was more perceived by non-alcoholic group. Conclusion: Alcoholic chronic pancreatitis presents with more local complications associated with chronic pancreatitis. Frey procedure is a safe and well accepted surgery in this group. Though they required more analgesic requirement in short term follow up, other aspects of quality of life are similar to non-alcoholic group.

RESUMO Racional: Embora o álcool seja a causa mais comum de pancreatite crônica em todo o mundo, a forma idiopática é prevalente na Índia. A história natural e a progressão da doença são diferentes entre esses dois grupos. Há escassez de dados comparando o resultado cirúrgico e a qualidade de vida entre eles. Objetivo: Avaliar as características clínicas, o resultado cirúrgico e a qualidade de vida entre esses dois grupos de pacientes. Método: Todos os pacientes com pancreatite crônica operados foram revisados ​​retrospectivamente. Resultados: Do total de 98 pacientes, 42 eram alcoolistas. O número de homens e a idade média no momento da operação foi significativamente maior nos alcoolistas. Tabagismo, taxa de internação pré-operatória e prevalência de complicações locais como massa inflamatória da cabeça do pâncreas, estenose biliar e hipertensão portal do lado esquerdo foram distintamente mais comuns no grupo de alcoolistas e o procedimento de Frey foi exigido mais comumente neste grupo. A média de internação pós-operatória e a taxa geral de complicações pós-operatórias foram comparáveis ​​entre os dois grupos. Ao longo de acompanhamento médio de 18 meses houve melhora significativa na qualidade de vida e pontuação de dor em ambos os grupos. A melhora no escore de funcionamento físico foi significativamente maior no grupo de alcoolistas, mas a necessidade de medicamentos analgésicos foi significativamente maior nos alcoolistas. No entanto, a perda de apetite foi mais percebida pelo grupo não alcoólico. Conclusão: A pancreatite crônica alcoólica se apresenta com mais complicações locais associadas à pancreatite crônica. O procedimento de Frey é operação segura e bem aceita neste grupo. Embora exigissem mais necessidade de analgésicos no acompanhamento em curto prazo, outros aspectos da qualidade de vida são semelhantes ao grupo não alcoólico.