Bilateral vision loss at high altitude: A diagnostic dilemma.

A young male patient of 22 years inducted at 11,000 feet altitude presented with a sudden onset bilateral diminution of vision associated with easy fatiguability and generalised weakness. Fundus examination revealed preretinal haemorrhages and Roth spots both eyes, owing to which differential diagnosis of high altitude retinopathy (HAR) and haematological disorders was considered. On systemic examination, he had pallor with massive splenomegaly. Haematological investigation revealed high total leucocyte count (TLC) 2.96 lac (normal 4000-11,000/uL) with peripheral blood smear showing increase in basophils, neutrophil precursors, myelocyte bulge, anaemia with no blasts suggestive of chronic myeloid leukaemia-chronic phase. Hence, a diagnosis of chronic myeloid leukaemia (chronic phase) with no features of tumour lysis syndrome was made. Patient was started on Tab hydroxyurea 50 mg twice a daily and managed by haemato-oncologist and required no further active ophthalmological intervention.

Evaluation of Regenerative Efficacy of Amnion and Chorion Membrane in Treatment of Mandibular Molar Furcation Defects: A Clinico-radiographic Study.

AIM: Amnion and chorion membranes possess unique inherited biological properties that enhance wound healing and may accelerate periodontal regeneration. The present study aims to evaluate and compare the efficacy of amnion and chorion membranes in the treatment of furcation defects. MATERIALS AND METHODS: A total of 20 patients were selected and were randomly allocated to group I and group II with 10 subjects in each group. Amnion and chorion membranes are placental-derived membranes that accelerate regeneration by having natural growth factors with their antimicrobial and inflammation reduction properties. Group I was treated using bone grafting with decalcified freeze-dried bone allograft (DFDBA) and placement of amnion as a membrane for guided tissue regeneration (GTR) whereas group II was treated using bone grafting with DFDBA and placement of chorion as a membrane for GTR. The patients were followed for clinical and radiographic parameters and were evaluated between 3 and 6 months after surgery. RESULT: In intragroup comparison, a significant difference was evident in both the groups for all the clinical and radiographic parameters within the groups. (p = 0.01) This means both amnion and chorion membranes showed statistically significant regenerative efficacy. In intergroup comparison, the results show that all the clinical parameters and radiographic parameters show no significant difference between the groups. CONCLUSION: The amnion and chorion membranes had similar regenerative efficacy in combination with DFDBA in patients with buccal degree II furcation defects in mandibular molars. CLINICAL SIGNIFICANCE: The amnion and chorion membranes have shown significant improvement in clinical and radiographic parameters when used for the treatment of buccal degree II furcation defects in mandibular molars. How to cite this article: Mallapragda S, Gupta R, Gupta S, et al. Evaluation of Regenerative Efficacy of Amnion and Chorion Membrane in Treatment of Mandibular Molar Furcation Defects: A Clinico-radiographic Study. J Contemp Dent Pract 2024;25(2):160-167.

De novo drug designing coupled with brute force screening and structure guided lead optimization gives highly specific inhibitor of METTL3: a potential cure for Acute Myeloid Leukaemia.

Expression of METTL3, a SAM dependent methyltransferase, which deposits m6A on mRNA is linked to poor prognosis in Acute Myeloid Leukaemia and other type of cancers. Down regulation of this epitranscriptomic regulator has been found to inhibit cancer progression. Silencing the methyltransferase activity of METTL3 is a lucrative strategy to design anticancer drugs. In this study 3600 commercially available molecules were screened against METTL3 using brute force screening approach. However, none of these compounds take advantage of the unique Y-shaped binding cavity of the protein, raising the need for de novo drug designing strategies. As such, 125 branched, Y-shaped molecules were designed by "stitching" together the chemical fragments of the best inhibitors that interact strongly with the METTL3 binding pocket. This results in molecules that have the three-dimensional structure and functional groups which enable it to fit in the METTL3 cavity like fingers in a glove, having unprecedented selectivity and binding affinities. The designed compounds were further refined based on Lipinski's rule, docking score and synthetic accessibility. The molecules faring well in these criteria were simulated for 100 ns to check the stability of the protein inhibitor complex followed by binding free energy calculation.Communicated by Ramaswamy H. Sarma.

Plasma Fibrinogen Degradation Products as the Nonsurgical Diagnostic Tool for Oral Submucous Fibrosis: A Systematic Review.

Aims and Objectives: Oral submucous fibrosis (OSMF) is known to be one of the most common premalignant conditions of the oral cavity. Areca nut (AN) is considered to be the disease's primary cause, while there are other potential causes as well. However, routine clinical practice has revealed that not all people who chew AN exhibit clinical signs of OSMF, and few people are reported to have it even without chewing AN. So, there must be other factors contributing to OSMF. Plasma fibrinogen degradation products (FDPs) have recently been discovered to be an early sign of this disease, indicating a potential link between the two. This review aims to examine the studies which have been published in the literature that explain the role of plasma FDPs in contributing to OSMF. Materials and Methods: An electronic search of the published literature was performed without publication year limitation in PubMed/ Medline, Scopus, Google Scholar, Web of Science, Science Direct, Embase, and Research gate databases, using mesh keywords like ('Oral submucous fibrosis' OR 'Oral submucous fibrosis') AND ('Fibrinogen degradation products' OR 'Plasma fibrinogen degradation products') AND ('Clinical grades' OR 'Histological grades') AND ('Diagnosis'). A manual search of all related journals was also done. We also referred to the reference lists of papers. The risk of bias was evaluated with the GRADE criteria (from the Grading of Recommendations Assessment, Development, and Evaluation Working Group). Results: The search revealed a total of 12 relevant studies from 1979 to 2022. Nine out of 12 studies demonstrated the definite presence of plasma FDPs in such cases. Conclusions: Although the studies documented in the literature showing evidence of plasma FDPs in patients with OSMF are very few in number, their detection signifies an important clinical finding. More research is still required in this aspect to establish stronger evidence.

Augmenting Career Longevity: An Analysis of Ergonomics Training Among 134 Neurological Surgeons.

BACKGROUND: Work-related pain among neurosurgeons remains understudied, yet can have long-term consequences which affect operative efficiency and efficacy, career longevity, and life outside of work. OBJECTIVE: This study provides insight into the extent of pain experienced by neurosurgeons and the effect of ergonomics training on pain. METHODS: An online survey pertaining to ergonomics and pain was sent to all neurosurgeons on the Council of State Neurosurgical Societies (CSNS) email distribution list. Statistical comparisons of age groups against pain levels and ergonomics training against pain levels, as well as multivariate linear regression of demographics, training, and operating factors against pain levels were performed. RESULTS: One hundred and thirty-four neurosurgeons responded to the survey. The mean average severity of pain across respondents was 3.3/10 and the mean peak severity of pain was 5.1/10. Among the reported peak pain severity scores, neurosurgeons with 21-30 years of operating experience had significantly higher pain scores than those with 11-20 years of experience (mean 6.2 vs. 4.2; P < 0.05), while neurosurgeons with more than 30 years of experience had significantly less pain than those with 21-30 years of experience (mean 4.4 vs. 6.2, P = 0.005). Training in ergonomics did not significantly improve respondents' reported peak or mean pain severities (17.9% reported having ergonomics training). CONCLUSIONS: Ergonomics training did not appear to make a difference in neurosurgeons' pain severities. This may signify a need to optimize ergonomics pedagogy to achieve observable benefits.

Infodemiology for oral health and disease: A scoping review.

INTRODUCTION: Increasing affordability, accessibility and penetration of internet services worldwide, have substantially changed the ways of gathering health-related information. This has led to the origin of concept infodemiology that allows the information to be collected and analysed in near real time. Globally, oral diseases affect nearly 3.5 billion people; thus, volume and profile of oral health searches would help in understanding specific community dental needs and formulation of pertinent oral health strategies. AIM: To review the published literature on infodemiological aspects of oral health and disease. METHODOLOGY: This scoping review was conducted in accordance with PRISMA-ScR guidelines. Electronic search engines (Google Scholar) and databases (PubMed, Web of science, Scopus) were searched from 2002 onwards. RESULTS: Thirty-eight articles were included in this review. The infodemiological studies for oral health and disease were mainly used in two domains. Out of 38 articles, 24 accessed the quality of available online information and 15 studied online oral health-related information seeking behaviour. CONCLUSION: The most commonly searched oral diseases were toothache, oral cancer, dental caries, periodontal disease, oral maxillofacial surgical procedures and paediatric oral diseases. Most of the studies belonged to developed countries and Google was the most researched search engine.

Trends in physician reimbursements and procedural volumes for radiosurgery versus open surgery in brain tumor care: an analysis of Medicare data from 2009 to 2018.

OBJECTIVE: Given its minimally invasive nature and effectiveness, stereotactic radiosurgery (SRS) has become a mainstay for the multimodal treatment of intracranial neoplasm. However, no studies have evaluated recent trends in the use of SRS versus those of open resection for the management of brain tumor or trends in the involvement of neurosurgeons in SRS (which is primarily delivered by radiation oncologists). Here, the authors used publicly available Medicare data from 2009 to 2018 to elucidate trends in the treatment of intracranial neoplasm and to compare reimbursements between these approaches. METHODS: By using CPT Professional 2019, the authors identified 10 open resection and 9 SRS codes (4 for neurosurgery and 5 for radiation oncology) for the treatment of intracranial neoplasm. Medicare payments (inflation adjusted) and allowed services (number of reimbursed procedures) for each code were abstracted from the Centers for Medicare and Medicaid Services Part B National Summary Data File (2009-2018). Payments per procedure and procedures per 100,000 Medicare enrollees were analyzed with linear regression and compared with tests for equality of slopes (α = 0.05). The average payment per procedure over the study period was compared by using the 2-tailed Welsh unequal variances t-test, and more granular comparisons were conducted by using ANOVA with post hoc Tukey honestly significant difference (HSD) tests. RESULTS: From 2009 to 2018, the number of SRS treatments per 100,000 Medicare enrollees for intracranial neoplasm increased by 3.97 cases/year (R2 = 0.99, p < 0.001), while comparable open resections decreased by 0.34 cases/year (R2 = 0.85, p < 0.001) (t16 = 7.5, p < 0.001). By 2018, 2.6 times more SRS treatments were performed per 100,000 enrollees than open resections (74.9 vs 28.7 procedures). However, neurosurgeon involvement in SRS treatment declined over the study period, from 23.4% to 11.5% of SRS treatments; simultaneously, the number of lesions treated per session increased from 1.46 to 1.84 (R2 = 0.98, p < 0.001). Overall, physician payments from 2013 to 2018 averaged $1816.08 (95% CI $1788.71-$1843.44) per SRS treatment and $1565.59 (95% CI $1535.83-$1595.34) per open resection (t10 = 15.9, p < 0.001). For neurosurgeons specifically, reimbursements averaged $1566 per open resection, but this decreased to $1031-$1198 per SRS session; comparatively, radiation oncologists were reimbursed even less (average $359-$898) per SRS session (p < 0.05 according to the Tukey HSD test for all comparisons). CONCLUSIONS: Over a decade, the number of open resections for intracranial neoplasm in Medicare enrollees declined slightly, while the number of SRS procedures increased greatly. This latter expansion is largely attributable to radiation oncologists; meanwhile, neurosurgeons have shifted their involvement in SRS toward sessions for the management of multiple lesions.

Patient satisfaction reviews for 967 spine neurosurgeons on Healthgrades.

OBJECTIVE: Patients are increasingly relying on independent physician rating websites (PRWs) to obtain information about healthcare providers. Healthgrades.com is a widely used PRW that allows patients to rate physicians on various metrics of performance and quality of care. This study categorically investigated the correlations between demographics of spine neurosurgeons and online ratings on Healthgrades to better understand the factors driving patient satisfaction in spine surgery in the United States. METHODS: In August-December 2019, the authors performed a retrospective data analysis using Healthgrades. The American Association of Neurological Surgeons (AANS) membership database was used to identify spine neurosurgeons in the United States and extract biographical and career data. Individuals with an academic practice were further investigated for academic rank, leadership, and fellowship training. Scores from eight patient satisfaction metrics (PSMs) were collected for each surgeon from Healthgrades. RESULTS: A total of 967 spine neurosurgeons were included in the study cohort. Patient satisfaction did not correlate with sex, PhD acquisition, academic status, or academic rank. Among those who were academic surgeons, completion of fellowship training was associated with higher ratings. Geographical location of practice did not influence patient satisfaction. Prolonged wait time was an independent predictor of decreased patient satisfaction and was a key confounding variable underlying trends seen with advanced career duration and age. CONCLUSIONS: Overall, patients rated spine neurosurgeons highly favorably on the Healthgrades website. Due to the emerging role of PRWs in locating and assessing providers, it is important for both patients and clinicians to understand the factors that impact patient experience.

Synthesis of Iron Oxide Palladium Nanoparticles and Their Catalytic Applications for Direct Coupling of Acyl Chlorides with Alkynes.

A new, magnetic, silica-based, palladium nanocatalyst has been synthesized and employed for the first time in the direct coupling of acyl chlorides with terminal alkynes to prepare a variety of ynones. The synthesized nanocomposite is an excellent heterogeneous catalyst for copper-free, phosphine-free, C-C bond formation through the Sonogashira reaction under aerobic conditions at room temperature without the use of any additives and inert conditions. The synthesized catalyst has been comprehensively characterized by various techniques, such as XRD, SEM, TEM, energy-dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, inductively coupled plasma, FTIR spectroscopy, vibrating sample magnetometry, and atomic absorption spectroscopy. This nanocatalyst can be magnetically recovered and reused in multiple runs without any noticeable loss in catalytic activity.

Assessment of oral health status of children with special needs in Delhi, India

Introduction: Children with special needs are considered to be a high risk group for dental diseases especially dental caries and periodontal diseases. Objective: Assessment of oral health status of children with special needs in Delhi, India. Material and methods: A cross sectional survey was conducted on 414 children with special needs belonging to four different disability groups i.e. Intellectually Disabled (ID), Physically Challenged, visually and hearing impaired. WHO Oral Health Assessment Form for children, 2013 was used for assessment of various parameters of oral health among the study population. Results: Of the 414 children, 305 were males and 109 females. Overall caries prevalence was 38%. Mean DMF value was 3.71 with ID children having higher mean than the other groups. A significant positive correlation was also observed between age and dental caries. Gingival condition was also worse in ID children and best in physically challenged ones. Highest numbers of trauma cases were recorded in visually impaired group. Delayed eruption of permanent teeth was most common in hearing impaired. 98.7% children required some form of dental treatment. Conclusion: Oral health of children with special needs was poor and urgent attention is required to plan a comprehensive dental health care programme for them.

A Rare Case Report of Neurofibromatosis I in HIV Positive Individual.

Neurofibroma is an uncommon benign tumour of neural tissue origin rarely presenting in the mouth and jaws and thereby attracting the attention of oral physicians. A 22-year-old male patient reported with a complaint of swelling in left middle one third region of face since 8-10 y which was slowly progressive in size. He had history of multiple dark brown pigmentation on skin associated with progressively enlarging multiple small nodular growths over the body and single firm nodular growth in left side of maxilla intraorally. He had history of tuberculosis at the age of one year which was treated completely and since last 2-3 y he was suffering from recurrent episodes of sore throat, fever, diarrhea, abdominal pain with vomiting and excessive weight loss. Radiographic findings showed irregular osteolytic lesions involving ramus and angle of mandible, zygomatic bone and posterior part of maxilla with displacement of teeth with abnormal soft tissue enhancement observed by advance imaging. On serological investigation he was HIV positive and histopathologically, diagnosed with Neurofibromatosis-1. Oral manifestations of neurofibromatosis have been reported in only 4% to 7% of affected persons. This article presents a rarest of rare case report of neurofibromatosis-I in HIV positive individual also involving maxilla, mandible as well as zygomatic arch.

Ameloblastoma: Cytopathologic profile of 12 cases and literature review.

BACKGROUND: Fine-needle aspiration cytology (FNAC) has been used as a diagnostic tool in evaluating suspected lesions. It shows a high diagnostic accuracy for diagnosing salivary gland lesions. AIM: The aim of this study was to highlight FNAC as an effective diagnostic tool in the presumptive diagnosis of ameloblastoma. MATERIALS AND METHODS: A total of 12 cases of ameloblastoma sampled by FNAC retrieved from the archives of the Oral Pathology Department were retrospectively studied. The smears were alcohol-fixed and stained with hematoxylin and eosin. All the 12 cases of FNAC had subsequent corresponding surgical incisional biopsy or excision specimens. RESULTS: Cytologically, seven cases were diagnosed as benign odontogenic tumor more in favor of ameloblastoma. All the 12 fine-needle aspiration cases were given a histopathologic work-up and diagnosed as ameloblastomas. Of these, the seven cytologically diagnosed benign odontogenic lesions were also confirmed to be ameloblastoma by both incisional biopsy as well as surgical excision. CONCLUSION: It was deduced from the above results that FNAC helps potentially in diagnosing ameloblastoma.

Structural basis for the redox sensitivity of the Mycobacterium tuberculosis SigK-RskA σ-anti-σ complex.

The host-pathogen interactions in Mycobacterium tuberculosis infection are significantly influenced by redox stimuli and alterations in the levels of secreted antigens. The extracytoplasmic function (ECF) σ factor σ(K) governs the transcription of the serodominant antigens MPT70 and MPT83. The cellular levels of σ(K) are regulated by the membrane-associated anti-σ(K) (RskA) that localizes σ(K) in an inactive complex. The crystal structure of M. tuberculosis σ(K) in complex with the cytosolic domain of RskA (RskAcyto) revealed a disulfide bridge in the -35 promoter-interaction region of σ(K). Biochemical experiments reveal that the redox potential of the disulfide-forming cysteines in σ(K) is consistent with its role as a sensor. The disulfide bond in σ(K) influences the stability of the σ(K)-RskAcyto complex but does not interfere with σ(K)-promoter DNA interactions. It is noted that these disulfide-forming cysteines are conserved across homologues, suggesting that this could be a general mechanism for redox-sensitive transcription regulation.

Cyclic AMP intoxication of macrophages by a Mycobacterium tuberculosis adenylate cyclase.

With 8.9 million new cases and 1.7 million deaths per year, tuberculosis is a leading global killer that has not been effectively controlled. The causative agent, Mycobacterium tuberculosis, proliferates within host macrophages where it modifies both its intracellular and local tissue environment, resulting in caseous granulomas with incomplete bacterial sterilization. Although infection by various mycobacterial species produces a cyclic AMP burst within macrophages that influences cell signalling, the underlying mechanism for the cAMP burst remains unclear. Here we show that among the 17 adenylate cyclase genes present in M. tuberculosis, at least one (Rv0386) is required for virulence. Furthermore, we demonstrate that the Rv0386 adenylate cyclase facilitates delivery of bacterial-derived cAMP into the macrophage cytoplasm. Loss of Rv0386 and the intramacrophage cAMP it delivers results in reductions in TNF-alpha production via the protein kinase A and cAMP response-element-binding protein pathway, decreased immunopathology in animal tissues, and diminished bacterial survival. Direct intoxication of host cells by bacterial-derived cAMP may enable M. tuberculosis to modify both its intracellular and tissue environments to facilitate its long-term survival.

Requirement of the mymA operon for appropriate cell wall ultrastructure and persistence of Mycobacterium tuberculosis in the spleens of guinea pigs.

We had recently reported that the mymA operon (Rv3083 to Rv3089) of Mycobacterium tuberculosis is regulated by AraC/XylS transcriptional regulator VirS (Rv3082c) and is important for the cell envelope of M. tuberculosis. In this study, we further show that a virS mutant (MtbdeltavirS) and a mymA mutant (Mtbmym::hyg) of M. tuberculosis exhibit reduced contents and altered composition of mycolic acids along with the accumulation of saturated C24 and C26 fatty acids compared to the parental strain. These mutants were markedly more susceptible to major antitubercular drugs at acidic pH and also showed increased sensitivity to detergent (sodium dodecyl sulfate) and to acidic stress than the parental strain. We show that disruption of virS and mymA genes impairs the ability of M. tuberculosis to survive in activated macrophages, but not in resting macrophages, suggesting the importance of the mymA operon in protecting the bacterium against harsher conditions. Infection of guinea pigs with MtbdeltavirS, Mtbmym::hyg, and the parental strain resulted in an approximately 800-fold-reduced bacillary load of the mutant strains compared with the parental strain in spleens, but not in the lungs, of animals at 20 weeks postinfection. Phenotypic traits were fully complemented upon reintroduction of the virS gene into MtbdeltavirS. These observations show the important role of the mymA operon in the pathogenesis of M. tuberculosis at later stages of the disease.

Disruption of mptpB impairs the ability of Mycobacterium tuberculosis to survive in guinea pigs.

Protein tyrosine kinases and tyrosine phosphatases from several bacterial pathogens have been shown to act as virulence factors by modulating the phosphorylation and dephosphorylation of host proteins. The identification and characterization of two tyrosine phosphatases namely MptpA and MptpB from Mycobacterium tuberculosis has been reported earlier. MptpB is secreted by M. tuberculosis into extracellular mileu and exhibits a pH optimum of 5.6, similar to the pH of the lysosomal compartment of the cell. To determine the role of MptpB in the pathogenesis of M. tuberculosis, we constructed a mptpB mutant strain by homologous recombination and compared the ability of parent and the mutant strain to survive intracellularly. We show that disruption of the mptpB gene impairs the ability of the mutant strain to survive in activated macrophages and guinea pigs but not in resting macrophages suggesting the importance of its role in the host-pathogen interaction. Infection of guinea pigs with the mutant strain resulted in a 70-fold reduction in the bacillary load of spleens in infected animals as compared with the bacillary load in animals infected with the parental strain. Upon reintroduction of the mptpB gene into the mutant strain, the complemented strain was able to establish infection and survive in guinea pigs at rates comparable to the parental strain. These observations demonstrate a role of MptpB in the pathogenesis of M. tuberculosis.