BA.1, BA.2 and BA.2.75 variants show comparable replication kinetics, reduced impact on epithelial barrier and elicit cross-neutralizing antibodies.

The Omicron variant of SARS-CoV-2 is capable of infecting unvaccinated, vaccinated and previously-infected individuals due to its ability to evade neutralization by antibodies. With multiple sub-lineages of Omicron emerging in the last 12 months, there is inadequate information on the quantitative antibody response generated upon natural infection with Omicron variant and whether these antibodies offer cross-protection against other sub-lineages of Omicron variant. In this study, we characterized the growth kinetics of Kappa, Delta and Omicron variants of SARS-CoV-2 in Calu-3 cells. Relatively higher amounts infectious virus titers, cytopathic effect and disruption of epithelial barrier functions was observed with Delta variant whereas infection with Omicron sub-lineages led to a more robust induction of interferon pathway, lower level of virus replication and mild effect on epithelial barrier. The replication kinetics of BA.1, BA.2 and BA.2.75 sub-lineages of the Omicron variant were comparable in cell culture and natural infection in a subset of individuals led to a significant increase in binding and neutralizing antibodies to the Delta variant and all the three sub-lineages of Omicron but the level of neutralizing antibodies were lowest against the BA.2.75 variant. Finally, we show that Cu2+, Zn2+ and Fe2+ salts inhibited in vitro RdRp activity but only Cu2+ and Fe2+ inhibited both the Delta and Omicron variants in cell culture. Thus, our results suggest that high levels of interferons induced upon infection with Omicron variant may counter virus replication and spread. Waning neutralizing antibody titers rendered subjects susceptible to infection by Omicron variants and natural Omicron infection elicits neutralizing antibodies that can cross-react with other sub-lineages of Omicron and other variants of concern.

Curcumin-loaded nanoparticles effectively prevent T4-induced oxidative stress in rat heart.

In this study, we report the cardioprotective effect of the glycerol monooleate (GMO) based nanocurcumin in both in vitro and in vivo conditions under a hyperthyroid state. The heart is one of the primary target organs sensitive to the action of thyroid hormone, and slight variations in the thyroid hormone serum concentrations result in measurable changes in cardiac performance. Hyperthyroidism-induced hypermetabolism is associated with oxidative stress and is an important mechanism responsible for the progression of heart failure. Curcumin has been known to play a protective role against oxidative stress-related diseases like Alzheimer's, asthma, and aging due to its antioxidant properties. Nevertheless, its potent biological activity has been hindered due to its poor bioavailability. To overcome this drawback, a GMO-based biodegradable nanoparticle (NP) formulation loaded with curcumin has been developed, and the protective effect of curcumin-loaded NPs was compared against the native drug. Oxidative stress parameters like reactive oxygen species (ROS) release, change in mitochondrial membrane permeability, lipid peroxidation (LPx), lactate dehydrogenase (LDH) release, and the activity and protein expression of the endogenous antioxidant enzymes like superoxide dismutase, catalase (CAT) and glutathione peroxidase were evaluated. The results from in vitro showed that curcumin-loaded NPs showed better DPPH and NO radical scavenging activity than native curcumin in a concentrations range of 2.5-20 µM. It was also observed that the nanoparticulate curcumin was comparatively more effective than native curcumin in protecting against ROS-induced membrane damage by reducing LPx and LDH leakage at low concentrations of 5-10 µM. Further, curcumin NPs performed better in facilitating the activities of antioxidant enzymes under in vitro and in vivo conditions with respect to time and concentrations, resulting in reduced cellular ROS levels. In this scenario, we anticipate that curcumin-loaded NPs can serve as a better antioxidant than its native counterpart in protecting the heart from oxidative stress-related diseases.

The spectrum of neurological manifestations and genotype-phenotype correlation in Indian children with Gaucher disease.

Gaucher disease (GD), one of the most frequent autosomal recessive lysosomal storage disorders, occurs due to bi-allelic pathogenic variants in the GBA1. Worldwide, the c.1448T>C (L483P) homozygous pathogenic variant is reported to be associated with neurological GD phenotype. Clinical distinction between GD1 and GD3 may be challenging due to subtle neurological features. Objective methods to evaluate neurological signs and saccades may help in early diagnosis. This study was conducted to assess the neurological phenotype, and its severity using a modified severity scoring tool (mSST), and the genotype-phenotype correlation. A total of 45 children aged 2 years 6 months to 15 years with a confirmed enzymatic and molecular diagnosis of GD with or without therapy were recruited. mSST tool was used to assess the severity of the neurological phenotype. A digital eye movement tracker (View Point Tracker) was used to assess eye movements. Clinical and genetic findings were analyzed. Out of 45 patients, 39 (86.7%) had at least one neurological phenotype detected using the mSST tool, with impairment of cognitive function (68.8%, 31/45) being the commonest feature. Thirty-two of 45 (71%) were assessed for saccadic eye movements using the eye tracker. Of these, 62.5% (20/32) had absent saccades. Four children (8.9%, 4/32) without clinical oculomotor apraxia had absent saccades on the viewpoint eye tracker. Overall, 77.7% (35/45), had homozygosity for c.1448T>C in GBA1 of which 91.4% (32/35) had neurological manifestations. Other alleles associated with neurological phenotype included c.1603C>T(p.R535C), c.1184C>T (p.S395F), c.115+1G>A (g.4234G>A), c.260G>A (p.R87Q) and c.1352A>G (p.Y451C). To conclude, in India, the c.1448T>C pathogenic variant in GBA1 is the commonest  and is associated with neurological phenotype of GD. Therefore, every patient of GD should be assessed using the mSST scoring tool for an early pick up of neurological features. The routine use of a viewpoint eye tracker in children with GD would be useful for early recognition of saccadic abnormalities.

Whole genome sequencing of spotted stem borer, Chilo partellus, reveals multiple genes encoding enzymes for detoxification of insecticides.

Spotted stem borer, Chilo partellus, is the most important constraint for increasing the production and productivity of maize and sorghum, the two major coarse cereals in Asia and Africa. The levels of resistance to this pest in the cultivated germplasm are low to moderate, and hence, farmers have to use insecticides for effective control of this pest. However, there is no information on the detoxification mechanisms in C. partellus, which is one of the constraints for deployment of appropriate insecticides to control this pest. The ability to detoxify insecticides varies across insect populations, and hence, we sequenced different populations of C. partellus to identify and understand detoxification mechanisms to devise appropriate strategies for deployment of different insecticides for controlling this pest. Larval samples were sequenced from three different cohorts of C. partellus using the Illumina HiSeq 2500 platform. The data were subjected to identify putative genes that are involved in detoxification on insecticides in our cohort insect species. These studies resulted in identification of 64 cytochrome P450 genes (CYP450s), and 36 glutathione S-transferases genes (GSTs) encoding metabolic detoxification enzymes, primarily responsible for xenobiotic metabolism in insects. A total of 183 circadian genes with > 80% homolog and 11 olfactory receptor genes that mediate chemical cues were found in the C. partellus genome. Also, target receptors related to insecticide action, 4 acetylcholinesterase (AChE), 14 γ-aminobutyric acid (GABA), and 15 nicotinic acetylcholine (nAChR) receptors were detected. This is the first report of whole genome sequencing of C. partellus useful for understanding mode of action of different insecticides, and mechanisms of detoxification and designing target-specific insecticides to develop appropriate strategies to control C. partellus for sustainable crop production.

Utility of fetal whole exome sequencing in the etiological evaluation and outcome of nonimmune hydrops fetalis.

INTRODUCTION: Nonimmune hydrops fetalis (NIHF) has varied etiology. We assessed the etiological spectrum and evaluated the utility of fetal whole exome sequencing (fWES) for the diagnosis of NIHF. METHODS: In this prospective cohort study, we evaluated antenatally diagnosed fetuses with NIHF between July 2018 and December 2019 according to the routine diagnostic algorithm. Fetuses that remained undiagnosed after routine NIHF workup were subjected to fetal chromosomal microarray and/or WES. Pregnancies were followed up for clinical outcomes. RESULTS: Of the 45 fetuses, consanguinity and recurrent hydrops fetalis were observed in 13.3% (6/45) and 28.8% (13/45), respectively. Overall, an etiological diagnosis was possible in 75.5% (34/45) of fetuses, while the cause remained unknown in 24.4% (11/45). A genetic etiology was identified in 46.6% (21/45): aneuploidy and monogenic disorders in 28.8% (13/45) and 17.8% (8/45), respectively. fWES on 19 fetuses detected disease-causing variants in 42.1% (8/19). Nine novel variants were detected in RAPSN, ASCC1, NEB, PKD1L1, GUSB, and PIEZO1. Only 8.8% (4/45) of the cohort survived without morbidity. CONCLUSIONS: This study describes the etiological spectrum and the disease-causing variants in an Indian cohort of hydropic fetuses.

COVID-19 vaccination and the power of rumors: Why we must "Tune in".

Rumors have significantly affected immunization campaigns in the past. The ongoing COVID-19 vaccination program in India needs to frame public communication messages both to promote vaccine demand and update as well as counter COVID-related rumors. COVID-related rumors have had wide-ranging effects in the country, from stigmatization of health workers to a crash of prices in the poultry sector. Appropriate communication strategies are critical for tracking, negotiating, and shaping perceptions around the vaccines and the program. Issues that will shape perceptions around the vaccines include product development, prioritization strategies, program rollout activities, and adverse effects following immunization and adverse effects of special interest.

Altered Cervical Mucosal Gene Expression and Lower Interleukin 15 Levels in Women With Schistosoma haematobium Infection but Not in Women With Schistosoma mansoni Infection.

BACKGROUND: Schistosomiasis increases the risk of human immunodeficiency virus (HIV) acquisition in women by mechanisms that are incompletely defined. Our objective was to determine how the cervical environment is impacted by Schistosoma haematobium or Schistosoma mansoni infection by quantifying gene expression in the cervical mucosa and cytokine levels in cervicovaginal lavage fluid. METHODS: We recruited women with and those without S. haematobium infection and women with and those without S. mansoni infection from separate villages in rural Tanzania with high prevalences of S. haematobium and S. mansoni, respectively. Infection status was determined by urine and stool microscopy and testing for serum circulating anodic antigen. RNA was extracted from cervical cytobrush samples for transcriptome analysis. Cytokine levels were measured by magnetic bead immunoassay. RESULTS: In the village where S. haematobium was prevalent, 110 genes were differentially expressed in the cervical mucosa of 18 women with versus 39 without S. haematobium infection. Among the 27 cytokines analyzed in cervicovaginal lavage fluid from women in this village, the level of interleukin 15 was lower in the S. haematobium-infected group (62.8 vs 102.9 pg/mL; adjusted P = .0013). Differences were not observed in the S. mansoni-prevalent villages between 11 women with and 29 without S. mansoni infection. CONCLUSIONS: We demonstrate altered cervical mucosal gene expression and lower interleukin 15 levels in women with S. haematobium infection as compared to those with S. mansoni infection, which may influence HIV acquisition and cancer risks. Studies to determine the effects of antischistosome treatment on these mucosal alterations are needed.

Schistosomiasis and hydration status: Schistosoma haematobium, but not Schistosoma mansoni increases urine specific gravity among rural Tanzanian women.

OBJECTIVES: Schistosome infections can damage organs important for water homeostasis, especially the kidneys. Urogenital schistosomiasis (caused by Schistosoma haematobium) increases protein and blood in urine and intestinal schistosomiasis (caused by S. mansoni) affects total body water. However, no data exist on how different schistosome species affect urine specific gravity (USG), a hydration biomarker. Therefore, we assessed the relationship between S. haematobium- and S. mansoni-infected and uninfected women and USG in rural Tanzania. MATERIALS AND METHODS: Surveys were conducted and stool and urine samples were collected among 211 nonpregnant women aged 18-50. S. haematobium eggs were detected using the urine filtration method. S. mansoni eggs were detected using the Kato Katz method. USG was measured using a refractometer and analyzed as both a continuous and dichotomous variable. Regression (linear/logistic) models were estimated to test the relationship between infection and hydration status. RESULTS: The prevalence of S. haematobium was 5.9% and S. mansoni was 5.4% with no coinfections. In regression models, S. haematobium-infected women had significantly higher USG (Beta = 0.007 g mL-1 ; standard error = 0.002; p = 0.001) and odds (Odds ratio: 7.76, 95% CI: 1.21-49.5) of elevated USG (>1.020 g mL-1 ) than uninfected women, whereas S. mansoni-infected women did not. DISCUSSION: Schistosoma haematobium, but not S. mansoni, infection is associated with higher USG and risk of inadequate hydration. Future work should determine whether findings are attributable to parasite-induced debris in urine or urinary tract pathologies and signs of renal damage. Human and non-human primate studies using USG in schistosome-endemic areas should account for schistosomiasis.

Role of anesthesiologist in ex utero intrapartum treatment procedure: A case and review of anesthetic management.

The ex utero intrapartum treatment (EXIT) procedure is a rare form of perinatal resuscitation. It is basically a bridge therapy between partial delivery of the child and stabilization of its cardiorespiratory functions. This procedure has multiple anesthetic challenges including maternal anesthesia, maintenance of uteroplacental flow, tocolysis till the neonate is stabilized, management of postpartum hemorrhage, fetal, and neonatal anesthesia. This review also describes a case of cervical teratoma in fetus, for which the EXIT was performed in our institute. In addition to the case description, multiple concerns specific for EXIT procedure are discussed in this review.

Asparagine Synthetase deficiency-report of a novel mutation and review of literature.

Asparagine synthetase deficiency is a rare inborn error of metabolism caused by a defect in ASNS, a gene encoding asparagine synthetase. It manifests with a severe neurological phenotype manifesting as severe developmental delay, congenital microcephaly, spasticity and refractory seizures. To date, nineteen patients from twelve unrelated families have been identified. Majority of the mutations are missense and nonsense mutations in homozygous or compound heterozygous state. We add another case from India which harbored a novel homozygous missense variation in exon 11 and compare the current case with previously reported cases.

Glucose Transporter 1 Expression in Odontogenic Keratocyst, Dentigerous Cyst, and Ameloblastoma: An Immunohistochemical Study.

INTRODUCTION: An array of odontogenic lesions manifest in the maxillofacial region with variable presentations. The biological behavior of lesions, such as odontogenic keratocyst (OKC), dentigerous cyst (DC), and ameloblastoma (AM) always invite debate. Glucose transporter 1 (GLUT-1) is proven to be an indicator of metabolic behavior of several benign and malignant neoplasms. AIM: The purpose of this study was to evaluate the expression of GLUT-1 in OKC, DC, and AM to understand their metabolic behavior. MATERIALS AND METHODS: Immunohistochemical expression of GLUT-1 was evaluated in each of the 15 cases of OKC, DC, and AM. The number of labeled cells, staining intensity, and membrane or cytoplasmic expressions were the parameters assessed and analyzed using chi-square test. RESULTS: All cases showed positive GLUT-1 expression: 86.6% OKC showed more than 50% labeled cells followed by DC (40%) and AM (26.5%); 53.3% OKC showed strong intensity in comparison to AM, which showed weak intensity in 53.3% cases; 86.6% of OKCs showed both membrane and cytoplasmic expression followed by DC (40%) and AM (26.6%), whereas 73.3% of AM showed only membrane expression followed by DC (60%) and OKC (13.3%). CONCLUSION: Odontogenic keratocyst was found out to be more metabolically active followed by DC and AM.

GALNS mutations in Indian patients with mucopolysaccharidosis IVA.

Mucopolysaccharidosis IV A (Morquio syndrome A, MPS IVA) is a lysosomal storage disease caused by the deficiency of N-acetylgalactosamine-6-sulfatase (GALNS). The mutation spectrum in this condition is yet to be determined in Indians. We aimed to analyze the mutations in the GALNS gene in Asian Indians with MPS IVA. All the exons and the adjacent intronic regions of the gene were amplified and sequenced in sixty-eight unrelated Indian families. We identified 136 mutant alleles comprising of 40 different mutations. We report twenty-two novel mutations that comprise of seventeen missense (p.Asn32Thr, p.Leu36Arg, p.Pro52Leu, p.Pro77Ser, p.Cys79Arg, p.His142Pro, p.Tyr191Asp, p.Asn204Thr, p.Gly188Ser, p.Phe216Ser, p.Trp230Cys, p.Ala291Ser, p.Gly317Arg, p.His329Pro, p.Arg386Ser, p.Glu450Gly, p.Cys501Ser), three splice-site variants (c.120+1G>C, c.1003-3C>G, c.1139+1G>A), one nonsense mutation (p.Gln414*) and one frameshift mutation (p.Pro420Leufs*440). Eighteen mutations have been reported earlier. Among these p.Ser287Leu (8.82%), p.Phe216Ser (7.35%), p.Asn32Thr (6.61%) and p.Ala291Ser (5.88%) were the most frequent mutations in Indian patients but were rare in the mutational profiles reported in other populations. These results indicate that the Indian patients may have a distinct mutation spectrum compared to those of other populations. Mutant alleles in exon 1, 7 and 8 accounted for 44.8% of the mutations, and sequencing of these exons initially may be a cost-effective approach in Asian Indian patients. This is the largest study on molecular analysis of patients with MPS IVA reported in the literature, and the first report from India.

New Horizons and Prospects in Oral Cancer Detection.

Recent advancements in oral cancer detection prioritize non-invasive and minimally invasive techniques for efficient and accurate screening. This review outlines progress in methods such as narrow band imaging, fluorescence imaging, and optical coherence tomography, showing promise in early lesion detection. Biomarker detection in saliva and targeted nanoparticles enhance early diagnosis, while machine learning improves diagnostic accuracy. However, clinical validation and large-scale studies are needed for widespread adoption.

Correction: Carcinoma Ex Ameloblastoma of the Mandible: A Rare Case Report.

[This corrects the article DOI: 10.7759/cureus.49536.].

Unveiling the In Vitro Anti-Biofilm Potential of Lactobacillus rhamnosus Against Saliva-Based Pathogens: A Gender-Age-Area Specific Study.

Probiotics, like lactobacilli and bifidobacteria, benefit health by populating the digestive system, which houses numerous microbial species. Studies demonstrate their ability to inhibit biofilm formation, crucial in preventing oral conditions like dental caries. Our research evaluated a probiotic strain's anti-biofilm efficacy against oral pathogens in 45 individuals' saliva, alongside its biofilm-forming potential. Analysis revealed significant biofilm inhibition in 36 samples. Comparisons based on age, gender, and geography further supported these findings. We propose further exploration of probiotics tailored to specific demographics to enhance oral health outcomes, suggesting a promising avenue for preventing oral microbial diseases.

RNA editing in host lncRNAs as potential modulator in SARS-CoV-2 variants-host immune response dynamics.

Both host and viral RNA editing plays a crucial role in host's response to infection, yet our understanding of host RNA editing remains limited. In this study of in-house generated RNA sequencing (RNA-seq) data of 211 hospitalized COVID-19 patients with PreVOC, Delta, and Omicron variants, we observed a significant differential editing frequency and patterns in long non-coding RNAs (lncRNAs), with Delta group displaying lower RNA editing compared to PreVOC/Omicron patients. Notably, multiple transcripts of UGDH-AS1 and NEAT1 exhibited high editing frequencies. Expression of ADAR1/APOBEC3A/APOBEC3G and differential abundance of repeats were possible modulators of differential editing across patient groups. We observed a shift in crucial infection-related pathways wherein the pathways were downregulated in Delta compared to PreVOC and Omicron. Our genomics-based evidence suggests that lncRNA editing influences stability, miRNA binding, and expression of both lncRNA and target genes. Overall, the study highlights the role of lncRNAs and how editing within host lncRNAs modulates the disease severity.

Dry Mouth Dilemma: A Comprehensive Review of Xerostomia in Complete Denture Wearers.

Xerostomia, commonly known as dry mouth, presents a significant challenge for individuals wearing complete dentures, affecting their oral health and quality of life. This review explores the relationship between saliva and complete dentures, highlighting the varied management strategies for xerostomia. Saliva plays a critical role in denture retention, lubrication, and oral environment buffering. Complete denture wearers often experience reduced salivary flow, aggravating symptoms of xerostomia. Various management approaches are discussed, including general measures such as hydration and salivary stimulation techniques which aim to boost saliva production naturally. The use of salivary substitutes provides artificial lubrication and moisture to alleviate dry mouth discomfort. Oral lubricating devices, such as sprays, gels, and lozenges, offer relief by mimicking saliva's lubricating properties, thereby improving denture stability and comfort. This review addresses the etiology of xerostomia in complete denture wearers and explores preventive measures to reduce its impact. A comprehensive approach has been discussed for the management of xerostomia which will help to improve the oral health and well-being of complete denture wearers experiencing dry mouth.

Assessment of Pathology Domain-Specific Knowledge of ChatGPT and Comparison to Human Performance.

CONTEXT.­: Artificial intelligence algorithms hold the potential to fundamentally change many aspects of society. Application of these tools, including the publicly available ChatGPT, has demonstrated impressive domain-specific knowledge in many areas, including medicine. OBJECTIVES.­: To understand the level of pathology domain-specific knowledge for ChatGPT using different underlying large language models, GPT-3.5 and the updated GPT-4. DESIGN.­: An international group of pathologists (n = 15) was recruited to generate pathology-specific questions at a similar level to those that could be seen on licensing (board) examinations. The questions (n = 15) were answered by GPT-3.5, GPT-4, and a staff pathologist that recently passed their Canadian pathology licensing exams. Participants were instructed to score answers on a 5-point scale and to predict which answer was written by ChatGPT. RESULTS.­: GPT-3.5 performed at a similar level to the staff pathologist, while GPT-4 outperformed both. The overall score for both GPT-3.5 and GPT-4 was within the range of meeting expectations for a trainee writing licensing examinations. In all but one question, the reviewers were able to correctly identify the answers generated by GPT-3.5. CONCLUSIONS.­: By demonstrating the ability of ChatGPT to answer pathology-specific questions at a level similar to (GPT-3.5) or exceeding (GPT-4) a trained pathologist, this study highlights the potential of large language models to be transformative in this space. In the future, more advanced iterations of these algorithms with increased domain-specific knowledge may have the potential to assist pathologists and enhance pathology resident training.

Excess nickel modulates activities of carbohydrate metabolizing enzymes and induces accumulation of sugars by upregulating acid invertase and sucrose synthase in rice seedlings.

The effects of increasing concentrations of nickel sulfate, NiSO(4) (200 and 400 µM) in the growth medium on the content of starch and sugars and activity levels of enzymes involved in starch and sugar metabolism were examined in seedlings of the two Indica rice cvs. Malviya-36 and Pant-12. During a 5-20 day growth period of seedlings in sand cultures, with Ni treatment, no definite pattern of alteration in starch level could be observed in the seedlings. In both roots and shoots of the seedlings Ni treatment led to a significant decrease in activities of starch degrading enzymes α-amylase, ß-amylase, whereas starch phosphorylase activity increased. The contents of reducing, non-reducing, and total sugars increased in Ni-treated rice seedlings with a concomitant increase in the activities of sucrose degrading enzymes acid invertase and sucrose synthase. However, the activity of sucrose synthesizing enzyme sucrose phosphate synthase declined. These results suggest that Ni toxicity in rice seedlings causes marked perturbation in metabolism of carbohydrates leading to increased accumulation of soluble sugars. Such perturbation could serve as a limiting factor for growth of rice seedlings in Ni polluted environments and accumulating soluble sugars could serve as compatible solutes in the cells under Ni toxicity conditions.