Mucosal-Type Chronic Otitis Media: Clinical Predictors of Postoperative Success.

OBJECTIVES: Chronic otitis media (COM) remains a global disease, a burden, and a challenge. Predicting its treatment's postoperative success based on clinical presentation has not been reported, particularly for the mucosal (tubotympanic/safe) type. METHODS:  A prospective descriptive study of patients with mucosal-type COM was done to identify clinical predictors of improved postoperative hearing outcomes and successful graft uptakes. RESULTS: Among the 110 ears studied, tympanoplasty was performed in 76 and cortical mastoidectomy with tympanoplasty in 34, based on six weeks of discharge-free or persistent discharge, respectively; all were treated with postoperative intranasal steroid spray. Eustachian tube dysfunction was noted in 96.4%. All patients with a history of ear discharge over five years had ossicular discontinuity, and those with persistent discharge had nonpatent aditus. Normal postoperative hearing was attained in most patients with less than one year of ear discharge. Surgical intervention within a year achieved normal hearing and graft success of 100% with type I tympanoplasty using the fascia alone in discharge-free ears and cortical mastoidectomy with tympanoplasty using cartilage-fascia graft in discharging ears, despite Eustachian tube dysfunction. In the latter group, graft success in type II tympanoplasty was 76.9%. CONCLUSION:  Ear discharge is the prime predictor of postoperative success in mucosal-type COM, as its duration and persistence dictate the time and type of surgical intervention. Duration of more than five years is directly proportional to pre-operative hearing loss with ossicular involvement and inversely proportional to postoperative hearing improvement, necessitating early surgical intervention, despite it being the mucosal or "safe type." Ear discharge-free for six weeks is an indicator of tympanoplasty. Persistent ear discharge, despite nonotogenic confounders, suggests aditus nonpatency, indicates the need for cortical mastoidectomy, and necessitates achieving its patency along with tympanoplasty. A surgical decision-making algorithm for the best possible surgical outcome in the chronic mucosal type of OM is also suggested.

Dissociation of H2O2 on water surfaces (ice and water droplets).

OH radicals are an important constituent of the atmosphere. Therefore, all reactions that act as a source of OH radicals are important. It is known that photo-dissociation of H2O2 is an important source of OH radicals in the atmosphere. In the present study, using Born-Oppenheimer molecular dynamics simulations, we have shown that the H2O2 molecule can dissociate thermally on water droplets, as well as on the surface of ice, to form OH radicals. Furthermore, the dissociation of H2O2 was found to be very fast (less than 50 fs) on the ice surface compared with on the water droplets. We believe this route for the formation of OH radicals could be more critical than photo-dissociation, as it can take place both during the day and at night, but further studies with more sophisticated theoretical approaches or experiments are required to confirm this hypothesis.

Elevated troponin levels as a predictor of mortality in patients with acute stroke: a systematic review and meta-analysis.

Background and Aim: The prognostic potential of cardiac troponin (cTn) in acute stroke patients has been a subject of ongoing debate. Our objective was to provide a comprehensive evidence for predicting mortality in acute stroke patients by using the elevated troponin levels. Methods: We conducted an extensive literature search, including PubMed, EMbase, and Trip Databases, covering studies published up to September 30, 2023. We computed risk ratios (RR) with 95% confidence intervals (CIs), performed sensitivity analysis, and conducted trial sequential analysis (TSA). Results: In total, 53 studies were analyzed, with 37 focusing on acute ischemic stroke (AIS), 11 on subarachnoid hemorrhage (SAH), and 7 on Intracerebral hemorrhage (ICH). Elevated cTn levels were significantly showed a higher predictive risk for In-hospital mortality in both AIS (RR=3.80, 95% CI; 2.82 to 5.12) as well as SAH (RR=2.23, 95% CI; 1.64 to 3.02). However, no significant predictive risk between elevated cTn levels and in-hospital mortality for ICH patients (RR=1.13, 95% CI: 0.46 to 2.79). A similar pattern was observed for elevated cTn levels, indicating an increased risk of last follow-up mortality for AIS (RR=2.41, 95% CI: 1.98 to 2.93) and SAH (RR=3.08, 95% CI: 2.25 to 4.21). Conclusion: Elevated troponin levels can serve as a promising predictive marker for both in-hospital and last follow-up mortality in AIS and SAH patients but not in ICH patients. Further prospective studies are needed to validate our findings along with exploring the preventive management of mortality in acute stroke settings.

The role, relevance and management of immune exhaustion in bovine infectious diseases.

Immune exhaustion is a state of immune cell dysfunction that occurs most commonly following chronic exposure to an antigen which persists after the immune response fails to remove it. Exhaustion has been studied most thoroughly with several cancers, but has also been observed in several chronic infectious diseases. The topic has mainly been studied with CD8+ T cells, but it can also occur with CD4+ T cells and other immune cell types too. Exhaustion is characterized by a hierarchical loss of effector cell functions, up-regulation of immuno-inhibitory receptors, disruption of metabolic activities, and altered chromatin landscapes. Exhaustion has received minimal attention so far in diseases of veterinary significance and this review's purpose is to describe examples where immune exhaustion is occurring in several bovine disease situations. We also describe methodology to evaluate immune exhaustion as well as the prospects of controlling exhaustion and achieving a more suitable outcome of therapy in some chronic disease scenarios.

Amphiphilic, lauric acid-coupled pluronic-based nano-micellar system for efficient glipizide delivery.

Glipizide; an insulin secretagogue belonging to the sulfonylurea class, is a widely used antidiabetic drug for managing type 2 diabetes. However, the need for life-long administration and repeated doses poses challenges in maintaining optimal blood glucose levels. In this regard, orally active sustained-release nano-formulations can be a better alternative to traditional antidiabetic formulations. The present study explored an innovative approach by formulating orally active sustained-release nano-micelles using the amphiphilic lauric acid-conjugated-F127 (LAF127) block copolymer. LAF127 block copolymer was synthesized through esterification and thoroughly characterized before being employed to develop glipizide-loaded nano-micelles (GNM) via the thin-film hydration technique. The optimized formulation exhibited mean particle size of 341.40 ± 3.21 nm and depicted homogeneous particle size distribution with a polydispersity index (PDI) < 0.2. The formulation revealed a surface charge of -17.11 ± 6.23 mV. The in vitro release studies of glipizide from developed formulation depicted a sustained release profile. Drug loaded micelles exhibited a substantial reduction in blood glucose levels in diabetic rats for a duration of up to 24 h. Notably, neither the blank nano-micelles of LAF127 nor the drug loaded micelles manifested any indications of toxicity in healthy rats. This study provides an insight on suitability of synthesized LAF127 block copolymer for development of effective oral drug delivery systems for anti-diabetic activity without any significant adverse effects.

Expression profiling of stemness markers in testicular germline stem cells from neonatal and adult Swiss albino mice during their transdifferentiation in vitro.

BACKGROUND: Spermatogonial stem cells (SSCs) were considered to be stem cells with limited potencies due to their existence in adult organisms. However, the production of spermatogonial stem cell colonies with broader differentiation capabilities in primary germ cell cultures from mice of select genetic backgrounds (C57BL6/Tg14, ddY, FVB and 129/Ola) indicated that SSCs from these strains were pluripotent. METHODS: We established primary cultures of SSCs from neonatal and adult Swiss 3T3 Albino mice. Stemness of SSC colonies were evaluated by performing real-time PCR and immunofluorescence analysis for a panel of chosen stemness markers. Differentiation potentials of SSCs were examined by attempting the generation of embryoid bodies and evaluating the expression of ectodermal, mesodermal and endodermal markers using immunofluorescence and real-time PCR analysis. RESULTS: Spermatogonial stem cells from neonatal and mature mice testes colonised in vitro and formed compact spermatogonial stem cell colonies in culture. The presence of stem cell markers ALPL, ITGA6 and CD9 indicated stemness in these colonies. The differentiation potential of these SSC colonies was demonstrated by their transformation into embryoid bodies upon withdrawal of growth factors from the culture medium. SSC colonies and embryoid bodies formed were evaluated using immunofluorescence and real-time PCR analysis. Embryoid body like structures derived from both neonatal and adult mouse testis were quite similar in terms of the expression of germ layer markers. CONCLUSION: These results strongly suggest that SSC-derived EB-like structures could be used for further differentiation into cells of interest in cell-based therapeutics.

Molecular insights into the variability and pathogenicity of Fusarium odoratissimum, the causal agent of Panama wilt disease in banana.

Fusarium wilt or Panama disease of banana caused by the hemibiotroph fungus, Fusarium odoratissimum, also known as F. oxysporum f.sp. cubense Tropical Race 4 is a serious threat to banana production worldwide. Being the world's largest grower and the origins of bananas in its northeast region, India is particularly vulnerable to this deadly fungus. In the present study, a total of 163 Fusarium isolates from infected banana were characterized for their pathogenic traits. Considering the variability in the Fusarium, the contaminated banana plants were collected from five districts of Uttar Pradesh and Bihar, two major primary infection states of India. All the isolates were screened using universal and specific primers to identify the F. odoratissimum strains. The identified F. odoratissimum strains were subjected to in vivo pathogenicity assessment using the susceptible banana cultivar 'Grand Naine'. The identified six most virulent strains were further characterized for their pathogenicity via in vivo bipartite interaction in terms of biochemical assays. Assessment of in vivo pathogenicity through qRT-PCR for three pathogenesis responsive genes, Six 1a (Secreted in xylem), Snf (Sucrose non-fermenting) and ChsV (Chitinase V), ascertained that the identified F. odoratissimum strains exhibit both intra- and inter-specific variability. The variability of F. odoratissimum strains signifies its importance for the assessment of spread of infection at specific sites to enable efficient management strategy of Fusarium wilt in banana.

Cerebrospinal Fluid Flow Parameters in Normal Subjects above 40 Years of Age.

Background Cerebrospinal fluid (CSF) flow is altered in many conditions like normal pressure hydrocephalus (NPH), aqueduct stenosis, or Chiari malformation. It is very important to know the normal CSF flow parameters for properly diagnosing these conditions. No data on CSF flow parameters of the Indian population are available. Hence, this study was undertaken to generate normative CSF flow parameters in the Indian population. Aim Our aim was to estimate normal CSF flow parameters across the cerebral aqueduct in Indian subjects over 40 years of age. Settings and Design This observational study was done in the tertiary care institute on subjects undergoing magnetic resonance imaging (MRI) for indications like headache and having normal MRI. Methods Phase-contrast quantitative flow sequence was done in 100 subjects perpendicular to the cerebral aqueduct on 3.0T MRI (Discovery 750w with GEM suit, GE, Milwaukee, WI, United States) using a dedicated 32-channel head coil with 10 cm/s velocity encoding. The region of interest was kept at the cerebral aqueduct in cross-section. The inbuilt software calculated flow-time and velocity-time graphs and calculated peak systolic velocity (PSV), peak diastolic velocity (PDV), systolic flow (SF), and diastolic flow (DF). Stroke volume (SV) was calculated by averaging systolic and DFs. p -Value < 0.05 was considered significant. Results Mean age was 53.72 ± 10.53 (40-78) years with 41 males and 59 females. PSV, PDV, SF, DF, and SV all showed a significant linear correlation with age with p -values of 0.001, 0.004, 0.009, <0.001, and <0.001, respectively. Only PDV ( p = 0.035) and DF ( p = 0.045) varied significantly with sex, values being higher in males. Conclusion All five CSF flow parameters studied vary positively with age, and this variation is linear. Normal decadal median values calculated for these parameters can act as baseline values for the local population and help in defining conditions like NPH.

Draft genome sequence of halotolerant plant growth-promoting Bacillus paralicheniformis MHN12.

Bacillus paralicheniformis MHN12 possesses a 4,245,453-base pair genome with 45.9% G + C content, including 1 CRISPR, 80 tRNA, 8 rRNA genes, and 4,418 predicted coding sequences . MHN12 exhibits high salinity tolerance and plant growth-promoting abilities, making it a promising bioinoculant for enhancing plant growth in saline soils.

Therapeutic proteins: developments, progress, challenges, and future perspectives.

Proteins are considered magic molecules due to their enormous applications in the health sector. Over the past few decades, therapeutic proteins have emerged as a promising treatment option for various diseases, particularly cancer, cardiovascular disease, diabetes, and others. The formulation of protein-based therapies is a major area of research, however, a few factors still hinder the large-scale production of these therapeutic products, such as stability, heterogenicity, immunogenicity, high cost of production, etc. This review provides comprehensive information on various sources and production of therapeutic proteins. The review also summarizes the challenges currently faced by scientists while developing protein-based therapeutics, along with possible solutions. It can be concluded that these proteins can be used in combination with small molecular drugs to give synergistic benefits in the future.

Deciphering the genetic landscape of seedling drought stress tolerance in wheat (Triticum aestivum L.) through genome-wide association studies.

Wheat is an important cereal crop constrained by several biotic and abiotic stresses including drought stress. Understating the effect of drought stress and the genetic basis of stress tolerance is important to develop drought resilient, high-yielding wheat cultivars. In this study, we investigated the effects of drought stress on seedling characteristics in an association panel consisting of 198 germplasm lines. Our findings revealed that drought stress had a detrimental effect on all the seedling characteristics under investigation with a maximum effect on shoot length (50.94% reduction) and the minimum effect on germination percentage (7.9% reduction). To gain a deeper understanding, we conducted a genome-wide association analysis using 12,511 single nucleotide polymorphisms (SNPs), which led to the identification of 39 marker-trait associations (MTAs). Of these 39 MTAs, 13 were particularly noteworthy as they accounted for >10% of the phenotypic variance with a LOD score >5. These high-confidence MTAs were further utilized to extract 216 candidate gene (CGs) models within 1 Mb regions. Gene annotation and functional characterization identified 83 CGs with functional relevance to drought stress. These genes encoded the WD40 repeat domain, Myb/SANT-like domain, WSD1-like domain, BTB/POZ domain, Protein kinase domain, Cytochrome P450, Leucine-rich repeat domain superfamily, BURP domain, Calmodulin-binding protein60, Ubiquitin-like domain, etc. Findings from this study hold significant promise for wheat breeders as they provide direct assistance in selecting lines harboring favorable alleles for improved drought stress tolerance. Additionally, the identified SNPs and CGs will enable marker-assisted selection of potential genomic regions associated with enhanced drought stress tolerance in wheat.

Fashion meets science: how advanced breeding approaches could revolutionize the textile industry.

Natural fibers have garnered considerable attention owing to their desirable textile properties and advantageous effects on human health. Nevertheless, natural fibers lag behind synthetic fibers in terms of both quality and yield, as these attributes are largely genetically determined. In this article, a comprehensive overview of the natural and synthetic fiber production landscape over the last 10 years is presented, with a particular focus on the role of scientific breeding techniques in improving fiber quality traits in key crops like cotton, hemp, ramie, and flax. Additionally, the article delves into cutting-edge genomics-assisted breeding techniques, including QTL mapping, genome-wide association studies, transgenesis, and genome editing, and their potential role in enhancing fiber quality traits in these crops. A user-friendly compendium of 11226 available QTLs and significant marker-trait associations derived from 136 studies, associated with diverse fiber quality traits in these crops is furnished. Furthermore, the potential applications of transcriptomics in these pivotal crops, elucidating the distinct genes implicated in augmenting fiber quality attributes are investigated. Additionally, information on 11257 candidate/characterized or cloned genes sourced from various studies, emphasizing their key role in the development of high-quality fiber crops is collated. Additionally, the review sheds light on the current progress of marker-assisted selection for fiber quality traits in each crop, providing detailed insights into improved cultivars released for different fiber crops. In conclusion, it is asserted that the application of modern breeding tools holds tremendous potential in catalyzing a transformative shift in the textile industry.

Natural fibers possess desirable properties, but they often lag behind synthetic fibers in terms of both quality and quantity. Genomic-assisted breeding has the potential to improve fiber quality traits in cotton, hemp, ramie, and flax. Utilizing available QTLs, marker-trait associations, and candidate genes can contribute to the development of superior fiber crops, underscoring the significance of advanced breeding tools.

Syringoid eccrine carcinoma of the nipple in a male patient with lymph node metastasis: A case report.

ABSTRACT: Syringoid eccrine carcinoma of nipple is an extremely rare neoplasm of adnexal origin with variable clinical appearance and diverse histologic findings. Syringoid eccrine carcinoma (SEC) is often a diagnostic dilemma due to its morphology and presentation. Usually, these malignancies arise as non-ulcerated nodules or plaques in the head & neck region including the trunk. They are locally aggressive and have an infiltrative growth pattern with a propensity for metastasis. SEC is characterized by syringoma-like tadpole morphology with ductular differentiation and predominant desmoplasia. Immunostaining in SEC is variable and this variability is believed to arise from the tumor's ability to differentiate along multiple routes including sweat secretory and or ductal differentiation. Here we present a rare case of SEC/ syringomatous carcinoma of nipple in a 51-year-old male breast with associated axillary lymph node metastasis. As per English literature, this is the second case of SEC in nipple of male patient.

Central Retinal Artery Occlusion in Young Adults at High Altitude: Thin Air, High Stakes.

Rana, Vipin, Pradeep Kumar, Sandeepan Bandopadhyay, Vijay K. Sharma, Meenu Dangi, Dattakiran Joshi, Sanjay Kumar Mishra, Satyabrat Srikumar, and V.A. Arun. Central retinal artery occlusion in young adults at high altitude: thin air, high stakes. High Alt Med Biol. 00:000-000, 2024.-We present five cases of young security personnel who were posted at high altitude (HA) for a duration of at least 6 months and presented with a sudden decrease of vision in one eye. The diagnosis of central retinal artery occlusion (CRAO) was made in all patients. Fundus fluorescein angiography and optical coherence tomography of the macula supported the diagnosis. None of these cases had any preexisting comorbidities. Erythrocytosis was noticed in all patients, and two of them had hyperhomocysteinemia. Four out of five patients showed either middle cerebral artery or internal carotid artery (ICA) thrombosis on computed tomography angiography. The patients were managed by a team of ophthalmologist, hematologist, vascular surgeon, and neurologist. In cases of incomplete ICA occlusion, patients were managed surgically. However, in the case of complete ICA occlusion, management was conservative with antiplatelet drugs. This case series highlights HA-associated erythrocytosis and hyperhomocysteinemia as important risk factors for CRAO in young individuals stationed at HA.

A review of hyaluronic acid-based therapeutics for the treatment and management of arthritis.

Hyaluronic acid (HA), a biodegradable, biocompatible and non-immunogenic therapeutic polymer is a key component of the cartilage extracellular matrix (ECM) and has been widely used to manage two major types of arthritis, osteoarthritis (OA) and rheumatoid arthritis (RA). OA joints are characterized by lower concentrations of depolymerized (low molecular weight) HA, resulting in reduced physiological viscoelasticity, while in RA, the associated immune cells are over-expressed with various cell surface receptors such as CD44. Due to HA's inherent viscoelastic property and its ability to target CD44, there has been a surge of interest in developing HA-based systems to deliver various bioactives (drugs and biologics) and manage arthritis. Considering therapeutic benefits of HA in arthritis management and potential advantages of novel delivery systems, bioactive delivery through HA-based systems is beginning to display improved outcomes over bioactive only treatment. The benefits include enhanced bioactive uptake due to receptor-mediated targeting, prolonged retention of bioactives in the synovium, reduced expressions of proinflammatory mediators, enhanced cartilage regeneration, reduced drug toxicity due to sustained release, and improved and cost-effective treatment. This review provides an underlying rationale to prepare and use HA-based bioactive delivery systems for arthritis applications. With special emphasis given to preclinical/clinical results, this article reviews various bioactive-loaded HA-based particulate carriers (organic and inorganic), gels, scaffolds and polymer-drug conjugates that have been reported to treat and manage OA and RA. Furthermore, the review identifies several key challenges and provides valuable suggestions to address them. Various developments, strategies and suggestions described in this review may guide the formulation scientists to optimize HA-based bioactive delivery systems as an effective approach to manage and treat arthritis effectively.

When Paul Berg meets Donald Crothers: an achiral connection through protein biosynthesis.

Outliers in scientific observations are often ignored and mostly remain unreported. However, presenting them is always beneficial since they could reflect the actual anomalies that might open new avenues. Here, we describe two examples of the above that came out of the laboratories of two of the pioneers of nucleic acid research in the area of protein biosynthesis, Paul Berg and Donald Crothers. Their work on the identification of D-aminoacyl-tRNA deacylase (DTD) and 'Discriminator hypothesis', respectively, were hugely ahead of their time and were partly against the general paradigm at that time. In both of the above works, the smallest and the only achiral amino acid turned out to be an outlier as DTD can act weakly on glycine charged tRNAs with a unique discriminator base of 'Uracil'. This peculiar nature of glycine remained an enigma for nearly half a century. With a load of available information on the subject by the turn of the century, our work on 'chiral proofreading' mechanisms during protein biosynthesis serendipitously led us to revisit these findings. Here, we describe how we uncovered an unexpected connection between them that has implications for evolution of different eukaryotic life forms.

Identification and molecular characterization of genes modulating progression of an oocyte from M-I to M-II in rat ovary.

BACKGROUND: To achieve oocyte competence for successful fertilization, bidirectional communication between oocyte and granulosa cells is crucial. The acquisition of meiotic competency in oocyte is facilitated by various regulatory genes however, expression pattern of these genes is not well documented during meiotic transition from Metaphase-I to Metaphase-II stage. Therefore, the present research analyzed the expression pattern of regulatory genes that are involved in the transition from M-I to M-II stages in rat oocyte. METHODS: The analysis of the data was conducted by applying an array of bioinformatic tools. The investigation of gene group interactions was carried out by employing the STRING database, which relies on co-expression information. The gene ontology (GO) analysis was performed utilizing the comparative GO database. Functional annotation for GO and pathway enrichment analysis were performed for genes involved in networking. The GO obtained through computational simulations was subsequently validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis. RESULTS: The findings of our study suggest that there is a distinct gene expression pattern in both the oocyte and granulosa cells. This pattern indicates that oocyte-secreted factors, such as BMP15 and GDF9, play a crucial role in regulating the progression of the meiotic cell cycle from the M-I to M-II stages. We have also examined the level of mRNA expression of genes including CYP11A1, CYP19A1, and STAR, which are crucial for the steroidogenesis. CONCLUSIONS: It is fascinating to observe that the oscillatory pattern of specific key genes may hold significance in the process of in vitro oocyte maturation, specifically during the transition from the M-I to M-II stage. It might be useful for determining biomarker genes and potential pathways that play a role in attaining oocyte competency, thereby aiding in the assessment of oocyte quality for the purpose of achieving successful fertilization.