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Mucormycosis is an angioinvasive infection caused by fungi of the Zygomycetes order. Rhizopus is the main pathogen responsible for 90% of cases of cerebral mucormycosis. The term rhinocerebral mucormycosis should be used only in the face, palatal, orbital, paranasal sinus, or brain area. Here, we present the case of a 42-year-old man who presented with complaints of pain and swelling in relation to the left upper back tooth region for the past 20 days. In this case, the patient was immunocompromised due to type II diabetes, as well as COVID hospitalization. This case enlightens the investigation, as well as the management protocol followed by post-operative rehabilitation. Early diagnosis and prompt treatment can significantly reduce the morbidity and mortality of these deadly fungal infections.
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Fossil fuels, such as coal and natural gas are typically used to generate electricity. Fossil fuels are non-renewable resources and harmful to the environment as they release greenhouse gases when burned. With the increased demand of cleaner sources for electricity generation, renewable sources need to be adopted. In India, Tirunelveli District, solar energy has been used in numerous industrial buildings as a source of electricity generation since the country benefits from high solar radiation throughout the year. However, solar energy is still not used in residential buildings despite a wide interest from the sector. This paper identified and assessed the barriers to implementing solar energy in residential buildings from the perspective of homeowners in India, Tirunelveli District. Based on a literature search followed by a ranking and factor analysis of data from a questionnaire survey, key barriers were identified. Ninety-one responses from residents in India, Tirunelveli District were obtained. The questionnaire results showed that the main barriers to adopting solar systems are financial limitations followed by limited solar suppliers in the region and lack of awareness of government incentives. The results of this study could be used to help suppliers and industrial stakeholders in understanding the major barriers and the government to put forward policies to promote solar systems for electricity generation in residential buildings.
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In the history of international relations, it has always been the plight of women to bear the brunt of pain and hardship caused by wars and conicts. Regardless of nation, community or class, the burden of deprivation and hardship often falls on women. While all civilians suffer when war breaks out, it is women and girls that face most risk and bore disproportionately large share of the burden of conict, but they had a marginal say in matters of peace. The author believes women's rights and empowerment fundamentally predicate on maintenance of peace and security. However, women do not have a hand at the ofcial political level of negotiations and in determining terms of agreements concerning peace and security. Women will have to claim their political space, will have to gain ofcial political power so that gender perspectives will be integrated into State and intra-State decisions on peace and security.
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Objective: To develop and validate a bedside dengue severity score in children less than 12 years for predicting severe dengue disease. Methods: We carried out an analysis of data on the clinical and laboratory parameters of patients with confirmed dengue, hospitalized in October, 2019 at our center. A comprehensive patient’s score was developed. Predictive models for severity were built using a forward step-wise method. This model was validated on the data of 312 children with dengue admitted during September- October, 2021. Results: Severe dengue was predicted by the dengue severity score with a sensitivity of 86.75% (95% CI 77.52%-93.19%), specificity of 98.25% (95% CI 95.56-99.52%), a positive predictive value of 95.34% (95% CI 92.18%-97.26%) and a negative predictive value of 94.74% (95% CI 87.16%-97.95%). The overall predictive accuracy was 95.2% (95% CI 92.19%- 97.28%). Conclusion: The proposed bedside dengue severity scoring system was found to have good validity. Validating the score in different settings and patient populations is suggested.
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Purpose: To describe the clinical outcomes of therapeutic penetrating keratoplasty (TPK) in patients with Pythium insidiosum keratitis following treatment with anti?pythium therapy (APT) consisting of linezolid and azithromycin. Methods: A retrospective review of medical records from May 2016 to December 2019 of patients with P. insidiosum keratitis was carried out. Patients who were treated with APT for a minimum of 2 weeks and then subsequently underwent TPK were included in the study. Data on demographic characteristics, clinical features, microbiology characteristics, and intraoperative details, postoperative outcomes were documented. Results: A total of 238 cases of Pythium keratitis were seen during the study period and 50 cases that satisfied the inclusion criteria were included. The median of the geometric mean of the infiltrate was 5.6 mm (IQR 4.0–7.2 mm). The patients received topical APT for a median of 35 days (IQR 25–56) prior to surgery. The most common indication of TPK was worsening keratitis (41/50, 82%). No recurrence of infection was observed. An anatomically stable globe was noted in 49/50 eyes (98%). The median graft survival rate was 2.4 months. A clear graft was present in 10 eyes (20%) with a final median visual acuity of 20/125 after a median follow?up period of 18.4 months (IQR 11–26 months). Graft size of less than 10 mm [OR: 5.824 (CI:1.292?41.6), P = 0.02] was found to be significantly associated with a clear graft. Conclusion: Performing TPK following the administration of APT has good anatomical outcomes. A smaller graft of <10 mm was associated with a higher chance of graft survival
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Background & objectives: Research studies in the 1970s reported that in pre-school children, undernutrition increased the risk of infections and infections aggravated undernutrition. Over decades, there has been a reduction in prevalence of undernutrition and improvement in access to healthcare for treatment of infections. A mixed longitudinal study was undertaken to assess whether over time there were any changes from the earlier reported effect of undernutrition prior to infection on the risk of morbidity and effect of morbidity on nutritional status in pre-school children. Methods: Pre-school (0-59 months of age) children from urban low- and middle-income families whose parents were willing to allow their participation in the study were enrolled. Information on sociodemographic profile of the families was collected at enrolment. Weight of all children and length in infants were recorded every month; length/height in children 12-59 months of age was recorded once in three months. Morbidity information was collected through fortnightly visits. Results: 3888 pre-school children were followed up in 74636 home visits. Among these children, underweight and wasting were associated with a small increase in risk of infections. The odds ratio for risk of infection for underweight children was 1.09 (95% CI: 1.02 to 1.16) and for wasting was 1.18 (95% CI: 1.08 to 1.29). The deterioration in Z scores for weight-for-age and body mass index-for-age in children during illness and convalescence was small but significant (P<0.001). Interpretation & conclusions: The increased risk of infections in undernourished children living in overcrowded tenements in areas with poor environmental hygiene was not significant, perhaps because the risk of infection in normally nourished children was also high. The deterioration in nutritional status following infection was small because of the ready access to and utilization of health and nutrition care.
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Background: Nearly one third of people who suffer major psychiatric disorders end up with a long- term disability and dependency. They are most likely to be non-adherent to medication due to various reasons including lack of knowledge or insight about their illness and treatment which in turn leads to exacerbation of their illness, reduce treatment effectiveness, or make them less responsive to subsequent treatment, multiple hospitalizations and poor quality of life. Materials and methods: A cross sectional study was carried out in outpatients attending the Psychiatry OPD using the consecutive sampling technique. Subjects meeting the ICD-10 Diagnostic criteria for psychiatric disorders, age 18 year and above, subjects willing to participate in the study were included. A structured proforma, the Drug attitude inventory and the WHO-QOL-BREF questionnaires were used for assessment. Results: Mean age of subjects = 38.07 + 11.07 years. Mean medication cost = Rs. 917.82 + 397.89. 87 subjects participated in the study and of them 48% were adherent to medication and 52% were non-adherent. 56% of males and 43% females were adherent to medication. There was significant association between the occupation and the type of family of the subjects and medication adherence (p<0.05). Majority of patients with medication non-adherence were seen in schizophrenia, delusional disorder, bipolar disorder, generalized anxiety disorder, obsessive-compulsive disorder and substance related disorder. Majority (44.5%) of them reported fear of side effects, followed by stopping the medication when feeling better (35.5%) as the reasons for non-adherence followed by cost, embarrassment, etc. There was significant association between the psychological and social quality of life and medication adherence (p<0.05). Conclusions: This study implicates the importance of psycho education about the diagnosis, prognosis, need for medication and the expected adverse effects which should be clearly explained to the patient. The therapeutic alliance is the most effective component in helping the patient maintain medication adherence and subsequently better quality of life.
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Purpose: To establish the normative data of the head and face measurements needed to design an appropriate spectacle frame for the Indian population. Methods: Indian subjects between 20 and 40 years were included in the study. Thirteen parameters were measured using the direct and indirect methods using ImageJ software. Photographs of subjects were captured in the primary gaze position, with the head turned toward the subject’s right and left by 90° from the primary gaze. Results: The mean ± standard deviation of age was 27.6 ± 5.7; 55.38% were males. An independent t?test showed a significant difference in nose width (P = 0.001), inter?pupillary distance (P = 0.032), and body mass index (P = .012) between males and females. Inner inter?canthi distance (P = .265), outer inter?canthi distance (P = .509), and frontal angles (P = .536) showed no significant difference. There is a significant difference in face width compared with the other studies. The mean head width of males (154.168 ± 9.121) was wider than that of females (145.431 ± 8.923). This suggests a smaller distance between the temples of a spectacle frame for females. Conclusion: Considering the above factors, there is a need for a customized spectacle frame design providing better optics, improved cosmesis, and comfort to the wearer
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Recent research has shown a strong correlation between gut dysbiosis and Alzheimer’s disease (AD). The purpose of this review is to investigate the relationship between gut dysbiosis, immune system activation, and the onset of AD and to examine current breakthroughs in microbiota-targeted AD therapeutics. A review of scientific literature was conducted to assess the correlation between gut dysbiosis and AD and the various factors associated. Gut dysbiosis produces an increase in harmful substances, such as bacterial amyloids, which makes the gut barrier and blood-brain barrier more permeable. This leads to the stimulation of immunological responses and an increase in cytokines such as interleukin-1? (IL-1?). As a result, gut dysbiosis accelerates the progression of AD. The review highlights the connection between gut dysbiosis and AD and the potential for microbiota-targeted therapies in AD treatment.
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Objectives To compare the epidemiological, clinical profle, intensive care needs and outcome of children hospitalized with SARS-CoV-2 infection during the frst and second waves of the pandemic. Methods This was a retrospective study of all children between 1 mo and 14 y, admitted to a dedicated COVID-19 hospital (DCH) during the frst (1st June to 31st December 2020) and second waves (1st March to 30th June 2021). Results Of 217 children, 104 (48%) and 113 (52%) were admitted during the frst and second waves respectively. One hundred ffty-two (70%) had incidentally detected SARS-CoV-2 infection, while 65 (30%) had symptomatic COVID-19. Comorbidities were noted in 137 (63%) children. Fifty-nine (27%) and 66 (30%) children required high-dependency unit (HDU) and ICU care respectively. Severity of infection and ICU needs were similar during both waves. High-fow oxygen (n=5, 2%), noninvasive ventilation [CPAP (n=34, 16%) and BiPAP (n=8, 5%)] and invasive ventilation (n=45, 21%) were respiratory support therapies needed. NIV use was more during the second wave (26% vs. 13%; p=0.02). The median (IQR) length (days) of DCH stay among survivors was longer during the frst wave [8 (6–10) vs. 5.5 (3–8); p=0.0001]. Conclusions Disease severity, associated comorbidities, PICU and organ support need and mortality were similar in the frst and second waves of the pandemic. Children admitted during the second wave were younger, had higher proportion of NIV use and shorter length of COVID-19 hospital stay.
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Polycystic Ovary Syndrome (PCOS) is one of the most prevalent endocrine disorder in women of reproductive age characterized by hyperandrogenism (HA). Current treatment options for PCOS are either with adverse effects or ineffective. Saptasaram kashayam (SK), an ayurvedic formulation is often been a safe traditional alternative medicine to improve the PCOS symptoms as well as its pathological development. However, its principle phytoconstituents or underlying mechanisms have not been investigated. In order to achieve this, the current study systematically utilized computational tools, network pharmacology approaches and molecular docking studies. All identified phytoconstituents of SK were screened by QikProp ADME prediction and 47 were selected based on oral bioavailability and drug likeliness scores. Their 3D structures were submitted to three online target fishing webservers PharmMapper, ChemMapper and Swiss Target Prediction which produced 1084 biological targets for SK comprehensively. 350 known PCOS therapeutic targets were retreived as common targets from three different interrogative disease centric bioinformatic platforms DisGeNET, OMIM and GeneCards. Intersection of 1084 biological targets of SK and 350 PCOS therapeutic targets produced, 88 potential therapeutic targets of SK against PCOS. STRING PPI and Compound-Target-Pathway networks were constructed and analysed using Cytoscape software. GO & KEGG pathway enrichment analysis was performed using DAVID database. 15 PCOS therapeutic target proteins were short listed from network analysis report- PIK3CA, PDPK1, AKT1, PIK3R1, STAT3, MAPK1, MAPK3, EGFR, AR, ESR1, ESR2, SHGB, NOS3, F2 & CREBBP. Targets that were likely to be inhibited/modulated by SK for treatment of PCOS were docked against the screened phytoconstituents and their respective standard inhibitors using GLIDE-SP of Schrodinger suite, Maestro version- 13.0. Results showed that Quercetin, Catechin, Boeravinone J, Genistein, Protocatechuic Acid, Gentisic Acid, Xanthoarnol, Luteolin, Boeravinone F, Tyrosine, Kaempferol, Dalbergioidin, etc exhibited good binding affinities when compared to standard drugs and might be responsible for synergistic/additive protective effect of SK against PCOS. Meanwhile PI3K-Akt signaling pathway, Prolactin signaling pathway, AGE-RAG diabetic complications, HIF-1 signaling pathway and Estrogen signaling pathway were found to be involving the hub genes of interest and in this way, they might be intervened during treatment of PCOS by SK. Present study succeeded in identifying the drug like principle phytoconstituents, probable PCOS therapeutic targets and the underlying molecular mechanism of SK apart from providing reliable evidence for therapeutic potential of SK against PCOS. However further validation by in vitro and in vivo investigations is necessary.
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Polycystic Ovary Syndrome (PCOS) is one of the most prevalent endocrine disorder in women of reproductive age characterized by hyperandrogenism (HA). Current treatment options for PCOS are either with adverse effects or ineffective. Saptasaram kashayam (SK), an ayurvedic formulation is often been a safe traditional alternative medicine to improve the PCOS symptoms as well as its pathological development. However, its principle phytoconstituents or underlying mechanisms have not been investigated. In order to achieve this, the current study systematically utilized computational tools, network pharmacology approaches and molecular docking studies. All identified phytoconstituents of SK were screened by QikProp ADME prediction and 47 were selected based on oral bioavailability and drug likeliness scores. Their 3D structures were submitted to three online target fishing webservers PharmMapper, ChemMapper and Swiss Target Prediction which produced 1084 biological targets for SK comprehensively. 350 known PCOS therapeutic targets were retreived as common targets from three different interrogative disease centric bioinformatic platforms DisGeNET, OMIM and GeneCards. Intersection of 1084 biological targets of SK and 350 PCOS therapeutic targets produced, 88 potential therapeutic targets of SK against PCOS. STRING PPI and Compound-Target-Pathway networks were constructed and analysed using Cytoscape software. GO & KEGG pathway enrichment analysis was performed using DAVID database. 15 PCOS therapeutic target proteins were short listed from network analysis report- PIK3CA, PDPK1, AKT1, PIK3R1, STAT3, MAPK1, MAPK3, EGFR, AR, ESR1, ESR2, SHGB, NOS3, F2 & CREBBP. Targets that were likely to be inhibited/modulated by SK for treatment of PCOS were docked against the screened phytoconstituents and their respective standard inhibitors using GLIDE-SP of Schrodinger suite, Maestro version- 13.0. Results showed that Quercetin, Catechin, Boeravinone J, Genistein, Protocatechuic Acid, Gentisic Acid, Xanthoarnol, Luteolin, Boeravinone F, Tyrosine, Kaempferol, Dalbergioidin, etc exhibited good binding affinities when compared to standard drugs and might be responsible for synergistic/additive protective effect of SK against PCOS. Meanwhile PI3K-Akt signaling pathway, Prolactin signaling pathway, AGE-RAG diabetic complications, HIF-1 signaling pathway and Estrogen signaling pathway were found to be involving the hub genes of interest and in this way, they might be intervened during treatment of PCOS by SK. Present study succeeded in identifying the drug like principle phytoconstituents, probable PCOS therapeutic targets and the underlying molecular mechanism of SK apart from providing reliable evidence for therapeutic potential of SK against PCOS. However further validation by in vitro and in vivo investigations is necessary.
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Strati?cation on the basis of caste is found all over India. Caste system as a form of strati?cation has a stronghold in urban slum areas also. City-ward migration for Scheduled Caste and Scheduled Tribe populations is synonymous with social development, as the city life offers socio-economic opportunities, better standards of living, educational and health facilities as compared to rural areas. The proportion of Scheduled Castes was higher in the slum areas (28.10%) compared to the population of Scheduled tribe in the country (21.19%). The state of Maharashtra has the largest number of Scheduled Castes and Scheduled Tribes living in urban slums. Andhra Pradesh had highest share of Scheduled Caste and Scheduled Tribe slum population in urban SC/ST population compared with other states
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Introduction: Fungal ball is a non-invasive sinus disease and the incidence of this disease has increased in recent years and also several case reports and case series have suggested a relationship with the accidental displacement of root into maxillary sinus. We report a case where fungal ball was removed along with the dental root fragment which was accidentally displaced into the maxillary sinus following traumatic dental extraction. A 32-years-oldCase Report: female patient presented to Maxillofacial Surgery Department with complaint of pain in the left orofacial region for one month. The patient had a history of traumatic extraction of posterior maxillary teeth 4 years back. On examination, no dental cause of pain was detected. On further evaluation, a foreign body within the left maxillary sinus was seen in the panoramic radiograph. Computed tomography images revealed displaced root in the left maxillary sinus with surrounding heterogenous soft tissue opacity. Following the detection of foreign body, patient underwent Functional Endoscopic Sinus Surgery (FESS) and the root was retrieved and the adjacent soft tissue specimen was sent for histopathological examination. The presence of fungus consistent with the Aspergillus species was confirmed. Conclusion: This article emphasizes the importance of atraumatic dental extraction, the association of fungal ball with displaced root and the utility of FESS in clearing the same.
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Background: Stress is a personal experience brought on by complex interactions between a person and their environment, so it cannot be avoided. It typically happens when a person’s situational demand exceeds their available resources. Additionally, it has been noted that excessive stress can hurt self-esteem, academic performance, and both personal and professional development. This study sought to determine the stress level, different stressors, and coping mechanisms used by undergraduate medical students. Materials and Methods: A cross-sectional study was done among first to final-year medical undergraduate students between January and June 2022 at a tertiary care institution in South India. 450 students enrolled in the first year to last year were included in the study through the purposeful sampling method. The medical Student Stressor Questionnaire was used to assess the stress levels among the study participants. The coping strategies were considered using a brief coping orientation to problems experienced (COPE) inventory. Cluster analysis used the K-means method. Results: A total of 278 out of the 450 students completed the questionnaire and returned it, yielding an overall response rate of61.78%. Of which 175 (62.95%) women respondents made up the majority of the study participants. The mean age of the participants was 20.15 ± 2.8 years. 45.32% ( n = 126) of the study participants belonged to the first year of their study, whereas 23.02% ( n = 64) belonged to the second year of their research. Academic stress was the primary stressor. The predominant coping strategies used were problem-focused and emotion-focused coping with stress. Conclusion: A variety of stress management techniques should be offered to help the students in better handling of the demanding professional course.
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Background@#Third molar extraction is the most commonly performed minor oral surgical procedure in outpatient settings and requires regional anesthesia for pain control. Extraction of the maxillary molars commonly requires both posterior superior alveolar nerve block (PSANB) and greater palatine nerve block (GPNB), depending on the nerve innervations of the subject teeth. We aimed to study the effectiveness of PSANB alone in maxillary third molar (MTM) extraction. @*Methods@#A sample size comprising 100 erupted and semi-erupted MTM was selected and subjected to study for extraction. Under strict aseptic conditions, the patients were subjected to the classical local anesthesia technique of PSANB alone with 2% lignocaine hydrochloride and adrenaline 1:80,000. After a latency period of 10 min, objective assessment of the buccal and palatal mucosa was performed. A numerical rating scale and visual analog scale were used. @*Results@#In the post-latency period of 10 min, the depth of anesthesia obtained in our sample on the buccal side extended from the maxillary tuberosity posteriorly to the mesial of the first premolar (15%), second premolar (41%), and first molar (44%). This inferred that anesthesia was effectively high until the first molars and was less effective further anteriorly due to nerve innervation. The depth of anesthesia on the palatal aspect was up to the first molar (33%), second molar (67%), and lateromedially; 6% of the patients received anesthesia only to the alveolar region, whereas 66% received up to 1.5 cm to the mid-palatal raphe. In 5% of the cases, regional anesthesia was re-administered. An additional 1.8 ml PSANB was required in four patients, and another patient was administered a GPNB in addition to the PSANB during the time of extraction and elevation. @*Conclusion@#The results of our study emphasize that PSANB alone is sufficient for the extraction of MTM in most cases, thereby obviating the need for poorly tolerated palatal injections.
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Background@#Knowledge of anatomy and morphometry of the patella and patellar tendon is crucial for the selection of bonepatellar tendon-bone (BTB) graft for anterior cruciate ligament reconstruction. Graft tunnel mismatch in BTB graft especially in patients with patella alta or baja can result in compromised fixation for the bone-to-bone healing. This complication can be avoided by proper templating of graft using parameters measured from magnetic resonance imaging (MRI). The study aimed to derive morphometric data from MRI and predict the suitability of BTB graft preoperatively. @*Methods@#MRI of 1,002 knees was chosen from database after applying the eligibility criteria, which included individuals in the age group of 18–50 years (both sexes) with the intact patella and patellar tendon. Individuals with pathologies of the knee joint and associated structures such as patellar fracture/dislocations, fractures of the distal femur and proximal tibia, and avulsion of the quadriceps tendon or patellar tendon were excluded. For analysis, 1.5 Tesla, proton density, and fat-suppressed sequences of sagittal and axial sections of T2-weighted MRI images were used. @*Results@#Mean age of the 1,002 patients was 35.45 years and there were 290 women and 712 men. Respective measurements were as follows: patella length, width, and thickness, 40.3 mm, 40.2 mm, and 18.6 mm, respectively; patellar tendon length, width, and insertional thickness, 45.2 mm, 27.2 mm, and 5.7 mm, respectively; Insall-Salvati ratio, 1.13; overall graft length, 90.2 mm; and effective tendon length, 26.1 mm. @*Conclusions@#A simple MRI analysis can give us valuable inputs on BTB graft morphometry. The values can also help us with the near-perfect graft harvest. The intraoperative complication of graft tunnel mismatch can be avoided by predicting the overall graft length, effective tendon length, tibial tunnel length, and patellar position using the measured parameters on MRI.
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Purpose@#NUT carcinoma (NC) is a solid tumor caused by the rearrangement of NUTM1 that usually develops in midline structures, such as the thorax. No standard treatment has been established despite high lethality. Thus, we investigated whether targeting the junction region of NUTM1 fusion breakpoints could serve as a potential treatment option for NC. @*Materials and Methods@#We designed and evaluated a series of small interfering RNAs (siRNAs) targeting the junction region of BRD4-NUTM1 fusion (B4N), the most common form of NUTM1 fusion. Droplet digital polymerase chain reaction using the blood of patients was also tested to evaluate the treatment responses by the junction sequence of the B4N fusion transcripts. @*Results@#As expected, the majority of NC fusion types were B4N (12 of 18, 67%). B4N fusion-specific siRNA treatment on NC cells showed specific inhibitory effects on the B4N fusion transcript and fusion protein without affecting the endogenous expression of the parent genes, resulting in decreased relative cell growth and attenuation of tumor size. In addition, the fusion transcript levels in platelet-rich-plasma samples of the NC patients with systemic metastasis showed a negative correlation with therapeutic effect, suggesting its potential as a measure of treatment responsiveness. @*Conclusion@#This study suggests that tumor-specific sequences could be used to treat patients with fusion genes as part of precision medicine for a rare but deadly disease.
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Recent advances in lymphatic imaging have provided novel insights into the lymphatic system. Interventional radiology has played a significant role in the development of lymphatic imaging techniques and modalities. Radiologists should be familiar with the basic physiology and anatomy of the lymphatic system to understand the imaging features of lymphatic disorders, which reflect their pathophysiology. This study comprehensively reviews the physiological and anatomical aspects of the human lymphatic system as well as the latest lymphatic imaging techniques.
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Lymphatic disorders encompass a broad spectrum of diseases involving the lymphatic system, ranging from traumatic lymphatic leaks to lymphatic malformations. Lymphatic disorders can be categorized into traumatic and non-traumatic disorders according to their etiology. These two categories may be further divided into subgroups depending on the anatomical location of the lymphatic pathology and their association with clinical syndromes. Thoracic duct embolization was a milestone in the field of lymphatic intervention that encouraged the application of percutaneous embolization techniques to treat leaks and reflux disorders in the lymphatic system. Additional access routes for embolization, including retrograde thoracic duct and transhepatic lymphatic access, have also been developed. This article comprehensively reviews a variety of options for the treatment of lymphatic disorders, from conservative management to the most recent embolization techniques.