Comparison of the Mesio-Distal Widths of the Maxillary and Mandibular Central Incisors Between Cleft Lip and Palate and Non Cleft Lip and Palate Individuals

Objective: To compare the mesiodistal widths of the maxillary and mandibular central incisors of cleft lip and palate individuals with non-cleft individuals, in a local population. Methodology: A total of 80 casts (40 of cleft patients and 40 normal) were selected by the department of orthodontics from January, 2021 to February, 2022, dividing them it into 4 groups by consecutive non-probability technique. The mesiodistal width of the maxillary and mandibular central incisors was measured with vernier caliper.  Independent t test was applied to compare the mesiodistal width of maxillary and mandibular central incisors between normal and cleft patients. Descriptive statistics were calculated for all four groups. Results: The mean MD width for the maxillary central incisors was 6.58 ± 1.16mm and 7.67 ±1.18mm for the CLP and control group respectively. The mean MD width for the mandibular central incisors was 4.22± 0.91 mm and 4.67 ± 0.9 mm for the CLP and control group respectively. The student t test showed a significant difference in the MD width of both the maxillary and mandibular central incisors between the CLP and control group. Conclusion: Patients suffering from cleft lip and palate are associated with diminutive central incisors in both jaws

Data on the role of accessible surface area on osmolytes-induced protein stabilization

AbstractThis paper describes data related to the research article “Testing the dependence of stabilizing effect of osmolytes on the fractional increase in the accessible surface area on thermal and chemical denaturations of proteins” [1]. Heat- and guanidinium chloride (GdmCl)-induced denaturation of three disulfide free proteins (bovine cytochrome c (b-cyt-c), myoglobin (Mb) and barstar) in the presence of different concentrations of methylamines (sarcosine, glycine-betaine (GB) and trimethylamine-N-oxide (TMAO)) was monitored by [ϴ]222, the mean residue ellipticity at 222nm at pH 7.0. Methylamines belong to a class of osmolytes known to protect proteins from deleterious effect of urea. This paper includes comprehensive thermodynamic data obtained from the heat- and GdmCl-induced denaturations of barstar, b-cyt-c and Mb

Frequency of immediate neonatal complications (hypoglycemia and neonatal jaundice) in late preterm and term neonates

Background: Evidence suggests that neonates born at 34-36 weeks should not be considered full-term neonates, given the magnitude of morbidities they experience compared with term infants. Neonates born at 34 to 36 weeks are at increased risk for early illness such as hypoglycemia and hyperbilirubinemia compared to term infants.Objective: This study\u27s objective was to determine the frequency of immediate neonatal complications (hypoglycemia and neonatal jaundice) in late preterm and term neonates.Subjects and methods: A serial descriptive case study was conducted at the private tertiary care hospital. Random samplings were taken, and the sample size was calculated on Epi Info software (Centers for Disease Control and Prevention, Atlanta, GA). All the eligible samples were taken into confidence following approval by the College of Physicians and Surgeons Pakistan\u27s institutional review board. A structured questionnaire was used in which demographic information of the patient was collected, and all neonates were closely observed for early targeted morbidities (hypoglycemia, hyperbilirubinemia).Results: A total of 215 neonates were born during the study period, of whom 108 (50.2%) were term babies and 107 (49.8%) late preterm babies. There were 122 (56.7%) male infants and 93 (43.3%) female infants. Jaundice was observed in 6.5% (n=7) of term neonates and 22.4% (n=24) of late preterm neonates (p\u3c0.0). Similarly, hypoglycemia was observed in only 4.6% (n=5) of term neonates and 15.9% (n=17) of late preterm neonates (p\u3c0.01).Conclusion: There is a significant association between gestational age and immediate neonatal complications of jaundice and hypoglycemia. Compared with term neonates, late preterm neonates are at a higher risk of neonatal jaundice and hypoglycemia. Gender and mode of delivery did not correlate to complications rate

Imaging and detecting intercellular tensile forces in spheroids and embryoid bodies using lipid-modified DNA probes

Cells continuously experience and respond to different physical forces that are used to regulate their physiology and functions. Our ability to measure these mechanical cues is essential for understanding the bases of various mechanosensing and mechanotransduction processes. While multiple strategies have been developed to study mechanical forces within two-dimensional (2D) cell culture monolayers, the force measurement at cell-cell junctions in real three-dimensional (3D) cell models is still pretty rare. Considering that in real biological systems, cells are exposed to forces from 3D directions, measuring these molecular forces in their native environment is thus highly critical for the better understanding of different development and disease processes. We have recently developed a type of DNA-based molecular probe for measuring intercellular tensile forces in 2D cell models. Herein, we will report the further development and first-time usage of these molecular tension probes to visualize and detect mechanical forces within 3D spheroids and embryoid bodies (EBs). These probes can spontaneously anchor onto live cell membranes via the attached lipid moieties. By varying the concentrations of these DNA probes and their incubation time, we have first characterized the kinetics and efficiency of probe penetration and loading onto tumor spheroids and stem cell EBs of different sizes. After optimization, we have further imaged and measured E-cadherin-mediated forces in these 3D spheroids and EBs for the first time. Our results indicated that these DNA-based molecular tension probes can be used to study the spatiotemporal distributions of target mechanotransduction processes. These powerful imaging tools may be potentially applied to fill the gap between ongoing research of biomechanics in 2D systems and that in real 3D cell complexes

Spiropyran as a potential molecular diagnostic tool for double-stranded RNA detection

Abstract Background Long double-stranded RNAs (dsRNAs) are duplex RNAs that can induce immune response when present in mammalian cells. These RNAs are historically associated with viral replication, but recent evidence suggests that human cells naturally encode endogenous dsRNAs that can regulate antiviral machineries in cellular contexts beyond immune response. Results In this study, we use photochromic organic compound spiropyran to profile and quantitate dsRNA expression. We show that the open form of spiropyran, merocyanine, can intercalate between RNA base pairs, which leads to protonation and alteration in the spectral property of the compound. By quantifying the spectral change, we can detect and quantify dsRNA expression level, both synthetic and cellular. We further demonstrate that spiropyrans can be used as a molecular diagnostic tool to profile endogenously expressed dsRNAs. Particularly, we show that spiropyrans can robustly detect elevated dsRNA levels when colorectal cancer cells are treated with 5-aza-2′-deoxycytidine, an FDA-approved DNA-demethylating agent used for chemotherapy, thus demonstrating the use of spiropyran for predicting responsiveness to the drug treatment. Conclusion As dsRNAs are signature of virus and accumulation of dsRNAs is implicated in various degenerative disease, our work establishes potential application of spiropyrans as a simple spectral tool to diagnose human disease based on dsRNA expression

Double-stranded RNA induction asa potential dynamic biomarkerfor DNA-demethylating agents

© 2022 The Author(s)Hypomethylating agents (HMAs), such as azacitidine and decitabine, induce cancer cell death by demethylating DNAs to promote the expression of tumor-suppressor genes. HMAs also reactivate the transcription of endogenous double-stranded RNAs (dsRNAs) that trigger the innate immune response and subsequent apoptosis via viral mimicry. However, the expression patterns of endogenous dsRNAs and their relevance in the efficacy of HMAs remain largely uninvestigated. Here, we employ amidine-conjugated spiropyran (Am-SP) to examine the dynamic expression pattern of total dsRNAs regulated by HMAs. By analyzing the bone-marrow aspirates of myelodysplastic syndrome or acute myeloid leukemia patients who received the HMAs, we find a dramatic increase in total dsRNA levels upon treatment only in patients who later benefited from the therapy. We further apply our approach in solid tumor cell lines and show that the degree of dsRNA induction correlates with the effectiveness of decitabine in most cases. Notably, when dsRNA induction is accompanied by increased expression of nc886 RNA, decitabine becomes ineffective. Collectively, our study establishes the potential application of monitoring the total dsRNA levels by a small molecule as an analytical method and a dynamic marker to predict the clinical outcome of the HMA therapy.N

Mitochondrial double-stranded RNAs as a pivotal mediator in the pathogenesis of Sjӧgren’s syndrome

Sjogren's syndrome (SS) is a systemic autoimmune disease that targets the exocrine glands, resulting in impaired saliva and tear secretion. To date, type I interferons (I-IFNs) are increas-ingly recognized as pivotal mediators in SS, but their endoge-nous drivers have not been elucidated. Here, we investigate the role of mitochondrial double-stranded RNAs (mt-dsRNAs) in regulating I-IFNs and other glandular phenotypes of SS. We find that mt-dsRNAs are elevated in the saliva and tears of SS patients (n = 73 for saliva and n = 16 for tears) and in salivary glands of non-obese diabetic mice with salivary dysfunction. Using the in-house-developed 3D culture of immortalized hu-man salivary gland cells, we show that stimulation by exoge-nous dsRNAs increase mt-dsRNAs, activate the innate immune system, trigger I-IFNs, and promote glandular phenotypes. These responses are mediated via the Janus kinase 1 (JAK1)/ signal transducer and activator of transcription (STAT) pathway. Indeed, a small chemical inhibitor of JAK1 attenuates mtRNA elevation and immune activation. We further show that muscarinic receptor ligand acetylcholine ameliorates auto -immune characteristics by preventing mt-dsRNA-mediated immune activation. Last, direct suppression of mt-dsRNAs re-verses the glandular phenotypes of SS. Altogether, our study underscores the significance of mt-dsRNA upregulation in the pathogenesis of SS and suggests mt-dsRNAs as propagators of a pseudo-viral signal in the SS target tissue.Y