The von Hippel-Lindau protein forms fibrillar amyloid assemblies that are mitigated by the anti-amyloid molecule Purpurin.

The von Hippel-Lindau protein (pVHL) is a tumor suppressor involved in oxygen regulation via dynamic nucleocytoplasmic shuttling. It plays a crucial role in cell survival by degrading hypoxia-inducible factors (HIFs). Mutations in the VHL gene cause angiogenic tumors, characterized as VHL syndrome. However, aggressive tumors involving wild-type pVHL have also been described but the underlying mechanism remains to be revealed. We have previously shown that pVHL possesses several short amyloid-forming motifs, making it aggregation-prone. In this study, using a series of biophysical assays, we demonstrated that a pVHL-derived fragment (pVHL104-140) that harbors the nuclear export motif and HIF binding site, forms amyloid-like fibrillar structures in vitro by following secondary-nucleation-based kinetics. The peptide also formed amyloids at acidic pH that mimics the tumor microenvironment. We, subsequently, validated the amyloid formation by pVHL in vitro. Using the Curli-dependent amyloid generator (C-DAG) expression system, we confirmed the amyloidogenesis of pVHL in bacterial cells. The pVHL amyloids are an attractive target for therapeutics of the VHL syndrome. Accordingly, we demonstrated in vitro that Purpurin is a potent inhibitor of pVHL fibrillation. The amyloidogenic behavior of wild-type pVHL and its inhibition provide novel insights into the molecular underpinning of the VHL syndrome and its possible treatment.

Intersection of network medicine and machine learning towards investigating the key biomarkers and pathways underlying amyotrophic lateral sclerosis: a systematic review.

BACKGROUND: Network medicine is an emerging area of research that focuses on delving into the molecular complexity of the disease, leading to the discovery of network biomarkers and therapeutic target discovery. Amyotrophic lateral sclerosis (ALS) is a complicated rare disease with unknown pathogenesis and no available treatment. In ALS, network properties appear to be potential biomarkers that can be beneficial in disease-related applications when explored independently or in tandem with machine learning (ML) techniques. OBJECTIVE: This systematic literature review explores recent trends in network medicine and implementations of network-based ML algorithms in ALS. We aim to provide an overview of the identified primary studies and gather details on identifying the potential biomarkers and delineated pathways. METHODS: The current study consists of searching for and investigating primary studies from PubMed and Dimensions.ai, published between 2018 and 2022 that reported network medicine perspectives and the coupling of ML techniques. Each abstract and full-text study was individually evaluated, and the relevant studies were finally included in the review for discussion once they met the inclusion and exclusion criteria. RESULTS: We identified 109 eligible publications from primary studies representing this systematic review. The data coalesced into two themes: application of network science to identify disease modules and promising biomarkers in ALS, along with network-based ML approaches. Conclusion This systematic review gives an overview of the network medicine approaches and implementations of network-based ML algorithms in ALS to determine new disease genes, and identify critical pathways and therapeutic target discovery for personalized treatment.

The centrality of redox regulation and reactive oxygen species sensing in abiotic and biotic stress acclimatization.

During land plant evolution, the number of genes encoding for components of the thiol redox regulatory network and the generator systems of reactive oxygen species (ROS) expanded, tentatively indicating a role in tailored environmental acclimatization. This hypothesis has been validated experimentally and theoretically during the last decades. Recent developments of dynamic roGFP-based in vivo sensors for H2O2 and the redox potential of the glutathione pool paved the way for dissecting the kinetics changes in these decisive parameters in response to environmental stressors. The versatile cellular redox sensory and response regulatory system monitors alterations in redox metabolism and controls the activity of redox target proteins, and thereby affects most, if not all, cellular processes ranging from transcription to translation and metabolism. This review exemplarily describes the role of the redox- and ROS-dependent regulatory network in realising the proper response to diverse environmental stresses. The selected case studies concern different environmental challenges, namely excess excitation energy, the heavy metal cadmium and the metalloid arsenic, nitrogen, or phosphate shortage as examples for nutrient deficiency, wounding, and nematode infestation. Each challenge affects the redox regulatory and ROS network, but the present state of knowledge also pinpoints to pressing open questions concerning the translation of redox regulation to environmental acclimatization.

1D speckle-learned structured light recognition.

In this Letter, we introduce a novel, to the best of our knowledge, structured light recognition technique based on the 1D speckle information to reduce the computational cost. Compared to the 2D speckle-based recognition [J. Opt. Soc. Am. A39, 759 (2022)10.1364/JOSAA.446352], the proposed 1D speckle-based method utilizes only a 1D array (1×n pixels) of the structured light speckle pattern image (n × n pixels). This drastically reduces the computational cost, since the required data is reduced by a factor of 1/n. A custom-designed 1D convolutional neural network (1D-CNN) with only 2.4 k learnable parameters is trained and tested on 1D structured light speckle arrays for fast and accurate recognition. A comparative study is carried out between 2D speckle-based and 1D speckle-based array recognition techniques comparing the data size, training time, and accuracy. For a proof-of-concept for the 1D speckle-based structured light recognition, we have established a 3-bit free-space communication channel by employing structured light-shift keying. The trained 1D CNN has successfully decoded the encoded 3-bit gray image with an accuracy of 94%. Additionally, our technique demonstrates robust performance under noise variation showcasing its deployment in practical cost-effective real-world applications.

Single-cell transcriptomics is revolutionizing the improvement of plant biotechnology research: recent advances and future opportunities.

Single-cell approaches are a promising way to obtain high-resolution transcriptomics data and have the potential to revolutionize the study of plant growth and development. Recent years have seen the advent of unprecedented technological advances in the field of plant biology to study the transcriptional information of individual cells by single-cell RNA sequencing (scRNA-seq). This review focuses on the modern advancements of single-cell transcriptomics in plants over the past few years. In addition, it also offers a new insight of how these emerging methods will expedite advance research in plant biotechnology in the near future. Lastly, the various technological hurdles and inherent limitations of single-cell technology that need to be conquered to develop such outstanding possible knowledge gain is critically analyzed and discussed.

In silico analysis of fungal prion-like proteins for elucidating their role in plant-fungi interactions.

Prion-like proteins (PrLPs) have emerged as beneficial molecules with implications in adaptive responses. These proteins possess a conserved prion-like domain (PrLD) which is an intrinsically disordered region capable of adopting different conformations upon perceiving external stimuli. Owing to changes in protein conformation, functional characteristics of proteins harboring PrLDs get altered thereby, providing a unique mode of protein-based regulation. Since PrLPs are ubiquitous in nature and involved in diverse functions, through this study, we aim to explore the role of such domains in yet another important physiological process viz. plant-microbe interactions to get insights into the mechanisms dictating cross-kingdom interactions. We have evaluated the presence and functions of PrLPs in 18 different plant-associated fungi of agricultural importance to unravel their role in plant-microbe interactions. Of the 241,997 proteins scanned, 3,820 (~ 1.6%) were identified as putative PrLPs with pathogenic fungi showing significantly higher PrLP density than their beneficial counterparts. Further, through GO enrichment analysis, we could predict several PrLPs from pathogenic fungi to be involved in virulence and formation of stress granules. Notably, PrLPs involved in (retro)transposition were observed exclusively in pathogenic fungi. We even analyzed publicly available data for the expression alterations of fungal PrLPs upon their interaction with their respective hosts which revealed perturbation in the levels of some PrLP-encoding genes during interactions with plants. Overall, our work sheds light into the probable role of prion-like candidates in plant-fungi interaction, particularly in context of pathogenesis, paving way for more focused studies for validating their role.

Decreased mRNA expression of NR1H3 and ABCA1 in pulmonary tuberculosis patients from population of Punjab, India.

BACKGROUND: Mycobacterium tuberculosis (MTB) is the causative organism of tuberculosis. Cholesterol is a crucial carbon source required for the survival of MTB in host cells. Transcription factor NR1H3 along with its important target genes ABCA1 and ApoE play important role in removal of extra cholesterol from cells. Changes in the gene expression of NR1H3, ABCA1 and ApoE can affect cholesterol homeostasis and thus the survival of MTB in host cells.Therefore, the present study was designed to analyze the mRNA expression of NR1H3, ABCA1 and ApoE in pulmonary TB (PTB) patients from the population of Punjab, India. METHODS AND RESULTS: In this study, mRNA expression of the transcription factor NR1H3 and its target genes ABCA1 and ApoE was analyzed in 89 subjects, including 41 PTB patients and 48 healthy controls (HCs) by real-time quantitative PCR. It was found that the mRNA expression of both NR1H3 and ABCA1 genes was significantly lower in TB patients than in HCs (p < 0.001). Even after sex-wise stratification of the subjects, mRNA expression of NR1H3 and ABCA1 was found to be down-regulated in both male and female TB patients. No significant difference was observed in expression of ApoE (p = 0.98). CONCLUSIONS: The present study found that the mRNA expression of NR1H3 and ABCA1 is down-regulated in TB patients from Punjab state of India.

Keto-enol tautomerism of ß-diketo molecules in the presence of graphitic materials through π-π stacking.

The pseudo aromatic structures of the enol forms of ß-diketo molecules are stabilized on the surface of graphitic materials through π-π interaction. This phenomenon has been studied through a relative binding energy calculation using density functional theory. The intermolecular interaction as well as the relative stability of the keto or enol tautomer is also influenced by the functional groups attached to the graphitic materials. The theoretical results are supported by spectroscopic evidence. Our study with three different graphitic materials, with a comparable extent of π-electrons and acid functionalities, reveals that π-π interaction is the main governing factor for the stability of the enol forms. Then comes the role of intermolecular H-bonding between the adsorbate and adsorbent. This can stabilize both the keto and enol tautomers, according to the arrangements of the functional groups and the geometry of the ß-diketo molecules. Acid groups on the adsorbent can enhance enolization through H-bonding, but an excess of functional groups may decrease the possibility of π-π interaction by disrupting the π-clouds of the graphitic surface and pushing the adsorbate and adsorbent away from each other beyond a π-π stacking distance. In that situation, H-bonding becomes crucial for determining the relative stability. Our results indicate that graphitic materials with acid functionalities across their edges, and ample π-cloud, are the most suitable catalysts for enolization.

Purification and partial characterization of a sperm motility-inhibitory protein of ram cauda epididymal plasma.

Mammalian sperm remain quiescent but fertile for several weeks in cauda epididymis. Although several sperm quiescent factors of epididymal plasma have been identified in goat, pig and cattle; however, little is known in sheep. In the present study, purification and characterization of a novel sperm quiescent protein of ovine cauda epididymal plasma (CEP) was carried out. The sperm quiescent protein was partially purified by hydroxyapatite gel adsorption chromatography followed by DEAE-sepharose® anion exchange chromatography. In the latter, the sperm quiescent activity was eluted both in 0.05 and 0.2 M potassium phosphate buffer (pH 7.5) fractions having a predominant protein of about 80 and 70 kDa with 87% and 63% homogeneity, respectively. The proteins were designated as motility-inhibitory factor of sheep I and II (MIFS-I and II), respectively. Significant (about 60%) inhibition of sperm motility was observed following treatment of cauda epididymal sperm with 6 and 12 µg/mL of partially purified MIFS-I and II, respectively. Specific activities of the partially purified MIFS-I and II were 563 and 261 U/mg of protein, while the fold-purification of the activity were 5119 and 2373, respectively. Both the proteins were heat-labile and the activity was completely lost following incubation at 100°C for 5 min. Further, the partially purified MIFS-I (5 µg/mL) caused significant reduction in in vitro sperm capacitation and slight decline in tyrosine phosphorylated p72 and p52 proteins; however the protein was nontoxic to sperm. Mass spectrometric analysis of MIFS-I revealed significant identity with human semaphorin 3D. Both dot blot and western blot analysis demonstrated cross-reactivity of MIFS-I with polyclonal anti-human SEMA3D antibody. It was concluded that the MIFS-I of ovine CEP was putative ovine semaphorin 3D protein having potent sperm quiescent and decapacitating activities and it possibly acts through inhibition of protein tyrosine phosphorylation.

Oculomotor Abnormalities and Aberrant Neuro-Developmental Markers: Composite Endophenotype for Bipolar I Disorder: Anomalies Oculomotrices et Marqueurs Neuro-Développementaux Aberrants : Endophénotype Composite du Trouble Bipolaire I.

BACKGROUND: Neurological soft signs (NSSs), minor physical anomalies (MPAs), and oculomotor abnormalities were plausible biomarkers in bipolar disorder (BD). However, specific impairments in these markers in patients after the first episode mania (FEM), in comparison with first-degree relatives (high risk [HR]) of BD and healthy subjects (health control [HC]) are sparse. AIM OF THE STUDY: This study aimed at examining NSSs, MPAs, and oculomotor abnormalities in remitted adult subjects following FEM and HR subjects in comparison with matched healthy controls. Investigated when taken together, could serve as composite endophenotype for BD. METHODS: NSSs, MPAs, and oculomotor abnormalities were evaluated in FEM (n = 31), HR (n = 31), and HC (n = 30) subjects, matched for age (years) (p = 0.44) and sex (p = 0.70) using neurological evaluation scale, Waldrop's physical anomaly scale and eye tracking (SPEM) and antisaccades (AS) paradigms, respectively. RESULTS: Significant differences were found between groups on NSSs, MPAs, and oculomotor parameters. Abnormalities are higher in FEM subjects compared to HR and HC subjects. Using linear discriminant analysis, all 3 markers combined accurately classified 72% of the original 82 subjects (79·2% BD, 56·70% HR, and 82·1% HC subjects). CONCLUSIONS: AS and SPEM could enhance the utility of NSSs, and MPAs as markers for BD. The presence of these abnormalities in FEM suggests their role in understanding the etiopathogenesis of BD in patients who are in the early course of illness. These have the potential to be composite endophenotypes and have further utility in early identification in BD.

Eye movement abnormalities and Atypical Neurodevelopmental markers as Composite Measurable components in the pathway between disease manifestation and genetics in Bipolar I DisorderPlain Language SummaryWhy was the study done?Neurological soft signs, Minor physical anomalies, and eye-movement abnormalities are known disease makers of Bipolar disorder but their utility in being intermediate markers between the disease manifestation and genetics has not been studied before. Hence we took up this study with the above aim.What did the researchers do?We compared the above-mentioned biomarkers between the patients diagnosed with first-episode mania (considered as early bipolar), the high-risk population (people with a family history of bipolar), and healthy subjects (without any self or family history of any psychiatric illnesses). Each group had 30 participants. We wanted to see if these markers taken together could predict the groups or classify the subjects into the three groups accurately.What did the researchers find?We found that in all the biomarkers there was a significant group difference between the the three groups. The abnormalities showed a pattern wherein they are higher in the first episode mania group compared to at-risk, and higher in at-risk compared to healthy subjects. When all these markers were combined and linear discriminant analysis was run, we noted they accurately classified 72% of the original participants (79·2% first episode bipolar 56·70% High risk, and 82·1% Healthy Subjects).What do the findings mean?The above findings indicate that the eye-movement or oculomotor abnormalities enhance the utility of neurodevelopmental markers as biomarkers of bipolar disorder. The presence of these abnormalities fairly early in the disease also means that they have a role in the etiopathogenesis of bipolar disorder. All the markers taken together can be composite measurable components in the pathway between disease manifestation and genetics in Bipolar I Disorder, and thus help in early identification.

Population structure and haplotype network analyses of Hyalomma anatolicum based on the large subunit ribosomal RNA (16S rRNA) gene.

Hyalomma anatolicum, an Anatolian hard tick is a well-recognized vector involved in the transmission of various pathogens to animals and humans. The present study elucidated the population structure and haplotype network of H. anatolicum based on the mitochondrial large subunit ribosomal RNA (16S rRNA) gene sequence. The population structure and haplotype network analysis of 75 sequences archived in the GenBank, including the 15 sequences generated herein, yielded 24 haplotypes. Haplotype 1 (Hap_1) was the predominant haplotype consisting of 45 sequences from India, China, Pakistan, Turkey, Egypt, Iraq, and Tajikistan. The complete haplotype network exhibited a stellate conformation, highlighting a recent population expansion. The overall dataset, together with the sequences corresponding to India, China, and Pakistan, showed a high haplotype (0.638 ± 0.065, 0.671 ± 0.103, 0.753 ± 0.099, and 0.854 ± 0.061, respectively) and low nucleotide (0.00407 ± 0.00090, 0.00525 ± 0.00196, 0.00680 ± 0.00233, and 0.00453 ± 0.00056, respectively) diversity, further emphasized a recent population expansion. The neutrality indices including Tajima's D, Fu and Li's D, and Fu and Li's F for the complete dataset (- 2.661, - 6.008, and - 5.649, respectively) as well as for the sequences from India (- 2.223, - 3.414, and - 3.567, respectively) were negative, suggesting deviation from neutrality and a recent population expansion. The present study provided novel insights into the population structure and haplotype networks of H. anatolicum based on the mitochondrial 16S rRNA gene, and the different tests inferred a low genetic differentiation and suggested a recent population expansion of this economically important tick species.

Ho3+ -doped BaGd2 ZnO5 green-emitting phosphor for solid-state lighting: synthesis, characterization, and photoluminescence properties.

In this work, we present the synthesis of a green-emitting series of BaGd2 ZnO5 :xHo3+ (0.5-3 mol%) phosphors using a high-temperature solid-state reaction method. Phase purity and crystal structure information were evaluated through X-ray powder diffraction patterns. Optical properties were examined through diffuse reflectance spectra, revealing that the prepared phosphor exhibited a band gap of 4.65 eV. The effect of Ho3+ doping on the morphology and ion distribution on the surface was assessed using scanning electron microscopy and time-of-flight secondary ion mass spectrometry techniques, respectively. The excitation spectra of the synthesized phosphor exhibited a charge transfer band and strong absorption transitions. The emission spectra displayed typical holmium emission characteristics, featuring a strong green emission band associated with f-f transitions from 5 F4 + 2 S2 → 5 I8 . Decay dynamics of the synthesized phosphor exhibited a single-exponential decay pattern, with lifetimes ranging from 0.103 to 0.053 ms. The intrinsic radiative lifetime, calculated through Auzel's fitting was determined to be 0.14 ms. Using the emission spectra, colorimetric behaviour was analyzed, revealing that the Commission Internationale de l'éclairage (CIE) coordinates exclusively lay within the green region at (0.285, 0.705), with an impressive colour purity of 99.6%. Given these marked properties, the synthesized phosphor exhibits great potential for a wide range of green-emitting applications, including displays, white light-emitting diodes, and security signage.

Molecular Docking and Molecular Dynamics Simulations of Synthesized Thiazole-Isatin-1,2,3-triazole Hybrids as Promising Inhibitors for DNA Gyrase and 14α-Sterol Demethylase.

In the present work, a new class of thiazole-isatin-1,2,3-triazole hybrids (5a-5p) and precursor alkyne hybrids (6a-6d) has been reported with their in-silico studies. After structural identifications using different spectroscopic technique such as FTIR, 1H and 13C NMR and HRMS, the synthesized hybrids were explored for their biological potential using molecular docking and molecular dynamics calculations. Molecular docking results revealed that compound 5j showed maximum binding energy i.e. -10.3 and -12.6 kcal/mol against antibacterial and antifungal enzymes; 1KZN (E. coli) and 5TZ1 (C. albicans), respectively.Top of FormBottom of Form Molecular dynamics simulations for the best molecule (100 ns) followed by PBSA calculations  suggested a stable complex of 5j with 5TZ1 with binding energy of -118.760 kJ/mol as compared to 1KZN (-94.593 kJ/mol). The mean RMSD values for the 1KZN with 5j complex remained approximately 0.175 nm throughout all the time span of 100 ns in the production stages and is in the acceptable range.  Whereas, 5TZ1 with 5j complex, RMSD values exhibited variability within the range of 0.15 to 0.25 nm.

Synthesis, Characterization, Antimicrobial and In Silico Studies of Isatin Schiff Base Linked 1,2,3-Triazole Hybrids.

A new series of isatin-Schiff base linked 1,2,3-triazole hybrids has been synthesized using CuAAC approach from (E)-3-(phenylimino)-1-(prop-2-yn-1-yl)indolin-2-one derivatives in high yield (73-91 %). These synthesized derivatives were characterized using FT-IR, 1H NMR, 13C NMR, 2D-NMR and HRMS spectral techniques. The in vitro antimicrobial activity assay demonstrated that most of the tested hybrids exhibited promising activity. Compound 5 j displayed significant antibacterial efficacy against P. aeruginosa and B. subtilis with MIC value of 0.0062 µmol/mL. While, 5 j also showed better antifungal potency against A. niger with MIC value of 0.0123 µmol/mL. The docking studies of most promising compounds were performed with the well-known antibacterial and antifungal targets i. e. 1KZ1, 5TZ1. Molecular modelling investigations demonstrated that hybrids 5 h and 5 l exhibited good interactions with 1KZN and 5TZ1, with binding energies of -9.6 and -11.0 kcal/mol, respectively. Further, molecular dynamics studies of the compounds showing promising binding interactions were also carried out to study the stability of complexes of these hybrids with both the targets.

A Review on the Traditional Applications, Phytochemistry, and Pharmacology of the Genus Physochlaina G. Don.

Physochlaina is a genus of flowering plants belonging to the family Solanaceae and consists of 10 species distributed in various Asian countries. The species of the genus have been traditionally used to cure a variety of illnesses due to their highly valuable medicinal properties, including cancer, asthma, cough, weakness, stomachache, diarrhea, swelling, spasms, toothache, boils, ulcers, rheumatic pain, chronic bronchitis, gastric problems, abdominal pain, palpitation, and insomnia. The species have gained significant attention due to their remarkable ethnopharmacological and ethnomedicinal significance. The researchers have isolated so far 71 biologically active secondary metabolites from different Physochlaina species, which include flavonoids, alkaloids, coumarins, phenolic acids, iridoids, and sterols. These compounds exhibit diverse biological activities, such as antibacterial, anti-oxidant, anti-inflammatory, cytotoxic, and anticancer properties. The present review has been compiled with the intention of providing a comprehensive overview of the botany, distribution, traditional uses, phytochemical profile, and biological activities of the genus Physochlaina for future exploration of plant-based drugs and therapeutic approaches. The present review contributes to understanding the significant pharmacological potential of Physochlaina species and unraveling their chemical composition, highlighting their relevance in developing therapeutic agents. Till date, numerous pharmacological properties and isolated phytochemicals of Physochlaina species that support the species traditional and ethnobotanical history have been documented in a number of scientific publications. However, greater emphasis should be paid to in vivo investigations on various extracts and their phytoconstituents as well as mechanistic analysis to help drug developers better understand how to use Physochlaina species as significant therapeutic resources for herbal formulations using various techniques.

Nascent pharmacological advancement in adamantane derivatives.

The adamantane moiety has attracted significant attention since its discovery in 1933 due to its remarkable structural, chemical, and medicinal properties. This molecule has a notable impact in the therapeutic field because of its "add-on" lipophilicity to any pharmacophoric moieties. As in the case of molecular hybridization, in which one pharmacophore is attached to another one(s) with a probability of increasing the biological activity, adding an adamantane unit improves the absorption distribution, metabolism and excretion properties of the resultant hybrid molecule. This review summarizes various reports highlighting the biological activities of adamantane-based synthetic compounds and their structure-activity relationship study. The information presented in this review may open up possible dimensions for adamantane-based drug development and discovery in the pharmaceutical industry after proper structural modifications.

Influence of the severity of periodontal disease on the outcome of non-surgical endodontic therapy: A prospective cohort study.

OBJECTIVE: To investigate the influence of severity of periodontal disease on periapical healing after non-surgical endodontic therapy (NSET). MATERIAL AND METHODS: In this prospective study, subjects (n = 45) requiring NSET in a mandibular molar tooth with the diagnosis of pulp necrosis and asymptomatic apical periodontitis exhibiting radiographic periapical index (PAI) score ≥ 3 and concomitant endodontic periodontal lesion (CEPL) without communication were enrolled. After dividing as per the classification of Periodontal and Peri-Implant Diseases and Conditions, subjects were equally allocated into three groups. Group I- only endodontic lesion {control: healthy periodontium (n = 15)}, Group II- CEPL having stage I and II periodontitis (n = 15) and Group III- CEPL having stage III periodontitis (n = 15). Standardized two-visit NSET was performed with 2% chlorhexidine gel as an intracanal medicament. Periodontal therapy was instituted wherever required. Subjects were recalled at 6-and 12-months for clinical and radiographic assessment. Chi-square test was performed to evaluate the difference between the groups. RESULTS: At 12-month follow-up, all teeth in the three study groups were asymptomatic. On radiographic evaluation of the periapical region, healing was observed in 80%, 47% and 50% of teeth in Groups I, Group II and Group III, respectively. However, the difference was not statistically significant between the groups (p = 0.150). CONCLUSION: The severity of periodontal disease had no influence on periapical healing after NSET in teeth with concomitant endodontic periodontal lesions without communication. CLINICAL RELEVANCE: Periodontal disease has significant impact on apical periodontitis however severity of the periodontitis does not negatively impact the apical periodontitis.

Novel cryotherapy technique for pulpotomy in mature permanent teeth with symptomatic irreversible pulpitis- a randomized controlled trial.

OBJECTIVES: To assess the effect of cryotherapy on haemostasis, post-operative pain, and the outcome of full pulpotomy performed in mature permanent teeth with symptomatic irreversible pulpitis. MATERIALS AND METHODS: The study included sixty mature permanent mandibular molar teeth with symptomatic irreversible pulpitis and no periapical rarefaction. After coronal pulp tissue amputation, teeth were randomly allocated to one of two groups (n = 30 each). In group I (conventional pulpotomy), a sterile cotton pellet moistened with 2.5% NaOCl was used for haemostasis. In group II (cryotherapy), the pulp chamber was continuously lavaged with 2.50C normal saline solution for haemostasis using an indigenous portable cryotherapy irrigation unit. Following haemostasis, the pulp was capped with mineral trioxide aggregate and the tooth was restored with resin composite. The time taken to achieve haemostasis was recorded. Preoperative and 24, 48 and 72 h postoperative pain was measured using the Numerical Rating Scale. The pulpotomy outcome was assessed at the 12-month follow-up. Data were analyzed using Fischer's exact test, two-sample t-test, two-sample Wilcoxon rank-sum test, Friedman Test, and Wilcoxon Signed Rank Test. RESULTS: The cryotherapy group achieved haemostasis in less time (p < 0.05). There was a significant pain reduction at 24 and 48 h in the cryotherapy group when compared with the conventional pulpotomy group (P < 0.005). The overall success rate of pulpotomy after 12 months was 88% (n = 22) in both study groups(p < 0.05). CONCLUSIONS: Cryotherapy application reduces postoperative pain and has no adverse effect on the outcome of pulpotomy in permanent teeth with symptomatic irreversible pulpitis. CLINICAL RELEVANCE: The cryotherapy can be incorporated in pulpotomy protocol as an adjunct to minimize post-operative pain.

Is COVID-19 an independent risk factor for the development of avascular necrosis of the hip? A retrospective study to evaluate the factors associated with avascular necrosis of the hip in patients who had COVID-19 infection.

PURPOSE: The cumulative effect of hyper-coagulative COVID-19 disease and using steroids leads to increased avascular necrosis (AVN) hip incidence. This study aims to correlate the various factors of COVID-19 infection with the occurrence of AVN hip. METHODS: It is a retrospective cross-sectional study of non-traumatic AVN hip patients with a history of COVID-19 infection. A total number of 50 patients satisfied the inclusion criteria. The following details were obtained: (a) patient's demographics, (b) COVID-19: interval of infection and groin pain, duration of symptoms, severity, steroid intake, (c) AVN hip: involved side, Ficat-Arlet staging. RESULTS: The mean age was 36.3 years (range: 20-60), and body mass index (BMI) was 25.13 kg/m2 (range: 18.50-31.50). There were 45 males and five females. Sixty percent (30) of patients managed at home, 24% (12) required admission into the ward, 2% (1) were in ICU only, and 14% (7) admitted to both ICU and ward. The mean interval of COVID-19 infection and onset of hip pain was 359.02 days (range: 10-822 days). Thirty-eight percent (19) patients required steroids (injection and oral), 46% (23) took steroids (oral only), whereas 16% (8) recovered without steroids. The stage of AVN correlated with the severity of COVID-19 infection (p-value -0.038) and significant improvement in VAS and HHS after treatment in each stage. The mean follow-up was 9.79 months (6-19 months). CONCLUSION: A low-dose steroid intake with moderate to severe COVID-19 infection produces an additive effect on the development of AVN hip. Most affected individuals were adult males, and stage II AVN was the most common, managed with bisphosphonates and core decompression for short intervals.

cGLRs Join Their Cousins of Pattern Recognition Receptor Family to Regulate Immune Homeostasis.

Pattern recognition receptors (PRRs) recognize danger signals such as PAMPs/MAMPs and DAMPs to initiate a protective immune response. TLRs, NLRs, CLRs, and RLRs are well-characterized PRRs of the host immune system. cGLRs have been recently identified as PRRs. In humans, the cGAS/STING signaling pathway is a part of cGLRs. cGAS recognizes cytosolic dsDNA as a PAMP or DAMP to initiate the STING-dependent immune response comprising type 1 IFN release, NF-κB activation, autophagy, and cellular senescence. The present article discusses the emergence of cGLRs as critical PRRs and how they regulate immune responses. We examined the role of cGAS/STING signaling, a well-studied cGLR system, in the activation of the immune system. The following sections discuss the role of cGAS/STING dysregulation in disease and how immune cross-talk with other PRRs maintains immune homeostasis. This understanding will lead to the design of better vaccines and immunotherapeutics for various diseases, including infections, autoimmunity, and cancers.