Patterns of quality assurance and treatment planning for stereotactic body radiation therapy in India - A survey.

AIM: The use of stereotactic body radiation therapy (SBRT) is an increasing trend in the country. The aim of this study is to gain knowledge on patterns of quality assurance (QA) and treatment planning (TP) aspects with respect to SBRT. MATERIALS AND METHODS: A questionnaire with multiple choice was designed to determine practices of SBRT covering areas such as years of experience, type of linear accelerator, tumor-motion strategies, calculation algorithm used in the TP system (TPS), the protocol used for small field dosimetry, the detector used for small field dosimetry and QA, respiratory management during delivery. The survey was sent to all radiotherapy institutes in the country having a minimum of one linear accelerator, and responses were analyzed. RESULTS: From June 2022 to December 2022, 265 responses to the SBRT survey were received with response rate as 60.4%. The most common reason for not adopting SBRT was reported as a lack of capability of treatment machines to deliver SBRT (61.6%). Lung (81.1%) was the most practiced site. The most common delivery unit was a conventional linear accelerator (83%); 6 MV FFF (85.7%) was mostly used energy; volumetric-modulated arc radiotherapy (VMAT) (91.5%) was mostly used delivery technique; most of the equipment (more than 91.5%) used multileaf collimator (MLC) leaf width ≤5 mm. The most popular methods used for motion strategies during computed tomography (CT) were motion-encompassing and breath-hold techniques used by 65 (62.5%) and 62 (59.6%) respondents, respectively. The most popular method used for respiratory management during delivery was breath-hold by 55 (52.4%) respondents. Most TPS are equipped with either Type-C or Type-B algorithms. Heterogeneity was observed in the QA protocol and acceptance criteria for analysis of patient-specific QA. CONCLUSION: The survey resulted in heterogeneity in QA and TP aspects among users of SBRT and demands for harmonizing the dosimetric aspects of SBRT in the country.

Dynamics of soil organic carbon of jhum agriculture land-use system in the heterogeneous hill of Arunachal Pradesh, India.

Land-use conversion affects soil organic carbon (SOC) dynamics. Therefore, an in-depth study of change in SOC, SOC pool, fractions of SOC and enzymatic activities of soil microbial biomass carbon (SMBC) and dehydrogenase (DHA) with the conversion of forest land to jhum, fallow jhum and settle cultivation use has been undertaken on the hills of Arunachal Pradesh of India. Geo-referenced soil samples from eight different locations, each from different land uses were collected at three depth. One part of the soil sample had been used for the analysis of SOC and its carbon fraction. The second portion was kept in a deep freezer for determining SMBC and DHA. The third part was used for the analysis of bulk density. The result revealed that the highest loss of SOC pool was recorded in jhum land (41.8 to 13.4%), and the labile carbon was also found to decrease in jhum land. The highest SMBC was observed on the surface soil of the natural forest; the highest DHA was found in the natural forest; and the lowest DHA was recorded in jhum land. This study found that the converting natural forest to jhum reduces SOC storage, enzymatic activities and C fractions significantly whereas fallow jhum shows sign of recovery because all of these parameters improved when compared to the jhum land-use system. This study also confirms that the fallow period helps restore the initial situation.

Discovery and Use of Long dsRNA Mediated RNA Interference to Stimulate Antiviral Protection in Interferon Competent Mammalian Cells.

In invertebrate cells, RNA interference (RNAi) acts as a powerful immune defense that stimulates viral gene knockdown thereby preventing infection. With this pathway, virally produced long dsRNA (dsRNA) is cleaved into short interfering RNA (siRNA) by Dicer and loaded into the RNA-induced silencing complex (RISC) which can then destroy/disrupt complementary viral mRNA sequences. Comparatively, in mammalian cells it is believed that the type I interferon (IFN) pathway is the cornerstone of the innate antiviral response. In these cells, dsRNA acts as a potent inducer of the IFN system, which is dependent on dsRNA length, but not sequence, to stimulate an antiviral state. Although the cellular machinery for RNAi is intact and functioning in mammalian cells, its role to trigger an antiviral response using long dsRNA (dsRNAi) remains controversial. Here we show that dsRNAi is not only functional but has a significant antiviral effect in IFN competent mammalian cells. We found that pre-soaking mammalian cells with concentrations of sequence specific dsRNA too low to induce IFN production could significantly inhibit vesicular stomatitis virus expressing green fluorescent protein (VSV-GFP), and the human coronaviruses (CoV) HCoV-229E and SARS-CoV-2 replication. This phenomenon was shown to be dependent on dsRNA length, was comparable in effect to transfected siRNAs, and could knockdown multiple sequences at once. Additionally, knockout cell lines revealed that functional Dicer was required for viral inhibition, revealing that the RNAi pathway was indeed responsible. These results provide the first evidence that soaking with gene-specific long dsRNA can generate viral knockdown in mammalian cells. We believe that this novel discovery provides an explanation as to why the mammalian lineage retained its RNAi machinery and why vertebrate viruses have evolved methods to suppress RNAi. Furthermore, demonstrating RNAi below the threshold of IFN induction has uses as a novel therapeutic platform, both antiviral and gene targeting in nature.

Automated objective surgical planning for lateral skull base tumors.

PURPOSE: Surgical removal of pathology at the lateral skull base is challenging because of the proximity of critical anatomical structures which can lead to significant morbidity when damaged or traversed. Pre-operative computed surgical approach planning has the potential to aid in selection of the optimal approach to remove pathology and minimize complications. METHODS: We propose an automated surgical approach planning algorithm to derive the optimal approach to vestibular schwannomas in the internal auditory canal for hearing preservation surgery. The algorithm selects between the middle cranial fossa and retrosigmoid approach by utilizing a unique segmentation of each patient's anatomy and a cost function to minimize potential surgical morbidity. RESULTS: Patients who underwent hearing preservation surgery for vestibular schwannoma resection (n = 9) were included in the cohort. Middle cranial fossa surgery was performed in 5 patients, and retrosigmoid surgery was performed in 4. The algorithm favored the performed surgical approach in 6 of 9 patients. CONCLUSION: We developed a method for computing morbidity costs of surgical paths to objectively analyze surgical approaches at the lateral skull base. Computed pre-operative planning may assist in surgical decision making, trainee education, and improving clinical outcomes.

Suramin, penciclovir, and anidulafungin exhibit potential in the treatment of COVID-19 via binding to nsp12 of SARS-CoV-2.

COVID-19, for which no confirmed therapeutic agents are available, has claimed over 48,14,000 lives globally. A feasible and quicker method to resolve this problem may be 'drug repositioning'. We investigated selected FDA and WHO-EML approved drugs based on their previously promising potential as antivirals, antibacterials or antifungals. These drugs were docked onto the nsp12 protein, which reigns the RNA-dependent RNA polymerase activity of SARS-CoV-2, a key therapeutic target for coronaviruses. Docked complexes were reevaluated using MM-GBSA analysis and the top three inhibitor-protein complexes were subjected to 100 ns long molecular dynamics simulation followed by another round of MM-GBSA analysis. The RMSF plots, binding energies and the mode of physicochemical interaction of the active site of the protein with the drugs were evaluated. Suramin, Penciclovir, and Anidulafungin were found to bind to nsp12 with similar binding energies as that of Remdesivir, which has been used as a therapy for COVID-19. In addition, recent experimental evidences indicate that these drugs exhibit antiviral efficacy against SARS-CoV-2. Such evidence, along with the significant and varied physical interactions of these drugs with the key viral enzyme outlined in this investigation, indicates that they might have a prospective therapeutic potential in the treatment of COVID-19 as monotherapy or combination therapy with Remdesivir.

Adenomatoid Odontogenic Tumor Mimicking a Dentigerous Cyst in Maxilla.

Aim: To present a case of adenomatoid odontogenic tumor (AOT) associated with impacted maxillary lateral incisor in a 12-year-old female that mimicked dentigerous cyst. Background: Adenomatoid odontogenic tumor (AOT) was first mentioned by Steensland in 1905, which is a rare tumor of odontogenic origin. Dreibladt in 1907 coined the term pseudo ameloblastoma. In 1948, Stafne considered it a distinct pathological entity. Case description: A 12-year-old female reported to the Department of Oral and Maxillofacial Surgery with the chief complaint of progressive swelling on the left maxillary anterior region for 6 months. The clinical and radiographical findings of the case represented a dentigerous cyst or unicystic ameloblastoma, but the histopathological interpretation was interpreted as AOT. Conclusion: The AOT is an unusual entity that is commonly misdiagnosed as a dentigerous or odontogenic cyst. Histopathology plays a vital role in diagnosis and further management. Clinical significance: The interest and relevance of the present case are the difficulties in diagnosing accurately based on the radiograph and histopathology. Both dentigerous cysts and AOT are entirely benign and encapsulated lesions, and enucleation poses no major difficulties. The case report highlights the importance of early diagnosis of neoplasm arising in odontogenic tissues. The fact that in cases of unilocular lesions surrounding the impacted tooth in the anterior maxillary region, AOT should also be considered as a differential diagnosis. How to cite this article: Pawar SR, Kshirsagar RA, Purkayastha RS, et al. Adenomatoid Odontogenic Tumor Mimicking a Dentigerous Cyst in Maxilla. Int J Clin Pediatr Dent 2022;15(6):770-773.

Impact of potential stimulants on asiaticoside and madecassoside levels and expression of triterpenoid-related genes in axenic shoot cultures of Centella asiatica (L.) Urb.

The triterpenoid saponins, asiaticoside and madecassoside from Centella asiatica (L.) Urb. are known to have a wide range of applications in pharmaceutical and cosmetic industries. The effect of addition of Potential Metabolite Stimulants (PMSs) - casein acid hydrolysate, meat peptone, salicylic acid, copper sulphate, and silver nitrate, on the concentrations of these saponins and transcript levels of associated genes encoding important biosynthetic enzymes, was assessed in axenic shoot cultures of C. asiatica. Among the stimulants, silver nitrate induced asiaticoside content approximately 6-fold increase in madecassoside levels, after three weeks post-treatment with a decrease in biomass compared to its control. Gene expression analysis of essential genes involved in triterpenoid synthesis such as ß-amyrin synthase showed an upregulation of approximately 50-fold at the third week of silver nitrate treatment compared to control. These findings suggest that silver nitrate can act as a metabolite stimulant, to enhance the formation of triterpenoids in axenic shoot culture of C. asiatica, which could be utilized in studying the regulation of terpenoid biosynthesis and biotechnological application for the increased production of these bioactive molecules.

How real is a virtual interview? Perspectives of orthopaedic surgery residency directors.

OBJECTIVE: As a result of COVID-19 pandemic, the 2021 US residency MATCH was devoid of the traditional in-person interviews. Herein, we assess the impact of Virtual Interviews (VIs) on resident selection, from the perspectives of Orthopedic Surgery (OS) Program Directors (PDs). MATERIALS AND METHODS: A 14-item survey was sent to PDs of ACGME-accredited OS residencies. Questions were designed to assess the pros, cons, and robustness of VIs compared to their antecedent in-person format. RESULTS: Forty-seven PDs responded to our survey. VIs antagonized PDs' ability to assess applicants' fit to program (76.6%), commitment to specialty (64%), and interpersonal skills (68.1%). This led to heavier dependence upon applicants' portfolios (64%). Almost all respondents (97.9%) found VIs to be more cost-efficient, saving a median of $3000 in interview-related expenses. Overall, only 8.5% of PDs were willing to conduct exclusive VIs in future cycles, compared to the majority in favor of dual formats (51.5%) or exclusive in-person interviews (40.4%). CONCLUSIONS: VIs have been an overall success, making most PDs opt for dual interview formats in future cycles. How this technology is further implemented in the future remains to be seen.

Gaps in facilities available at Community Health Centers/Rural Hospitals as per Indian public health standards - Study from Western Maharashtra.

BACKGROUND: The launch of the National Rural Health Mission (NRHM) gives us the opportunity to review the functioning and bring up the Community Health Centers (CHC) services to the level of Indian Public Health Standards and thus improve the lives of citizens. OBJECTIVES: Assessment of the gaps in the facilities available at Community health centers/Rural hospitals as per Indian Public health standards. METHODS: Facility based cross-sectional study was conducted in the Satara district of Maharashtra. RESULTS: This study in the majority showed that the gap in the delivery of healthcare according to IPHS. It was observed that the Funded CHCs had a better quality of services than the non-funded CHCs. The non-funded CHCs lacked essential emergency services. Along with ANC care, newborn care in the first few minutes of life is very crucial, but very little priority was given to the newborn care as those services were not as per norms. Specialists as well as paramedical and other support staff are deficient in both funded and non funded CHCs/rural hospitals (RHs). CONCLUSION: Standards were greatly influenced by funds delivered by IPHS itself. A staffing pattern is one of the important pillars in delivering various health services. A better salary, working place with continuous water supply, electricity, and cleanliness will improve the staffing pattern. Therefore, competent manpower and well-built infrastructure will help in the standard delivery of healthcare at CHC/RH and will thus serve the purpose of dispensing basic health services to every individual in the remotest areas.

Novel therapeutic intervention of coenzyme Q10 and its combination with pioglitazone on the mRNA expression level of adipocytokines in diabetic rats.

AIMS: Aim of the present study was to investigate the effect of co-administration coenzyme Q10 and pioglitazone on the mRNA expression of adipocytokines in white adipose tissues of chemically induced type 2 diabetes mellitus in rats. MAIN METHODS: Diabetes was induced by administration of streptozotocin (65 mg/kg, i.p.), followed by nicotinamide (110 mg/kg, i.p.) 15 min later. The diabetic rats were treated coenzyme Q10 (Q10, 10 mg/kg, p.o.) or pioglitazone (PIO, 20 mg/kg, p.o.) alone and their combination for four weeks. Biochemical parameters like FBS level, insulin and HbA1c along with tissue levels of MDA, SOD, CAT and GSH were estimated. The mRNA levels of ADIPOQ, RBP4, RETN, IL-6 and TNF-α in White Adipose Tissue (WAT) were measured. KEY FINDINGS: Treatment with Q10 + PIO showed a significant reduction in the levels of FBS, HbA1c and a significant increase in insulin levels as compared to normal control group. Additionally, there was a significant change in the levels of biomarkers of oxidative stress after treatment with Q10 + PIO as compared to streptozotocin-nicotinamide group. Treatment with Q10 + PIO also significantly altered the mRNA expression of ADIPOQ, RETN, IL-6 and TNF-α when compared to monotherapy. However, mRNA expression of RBP4 did not alter in Q10 + PIO treated animal as compared to Q10 or PIO alone. SIGNIFICANCE: It is concluded that co-administration of Q10 and PIO has been shown the better therapeutic effect on the mRNA expression of adipocytokines and oxidative stress parameters as compared to either Q10 or PIO.

Blood circulation of soft nanomaterials is governed by dynamic remodeling of protein opsonins at nano-biointerface.

Nanomaterials in the blood must mitigate the immune response to have a prolonged vascular residency in vivo. The composition of the protein corona that forms at the nano-biointerface may be directing this, however, the possible correlation of corona composition with blood residency is currently unknown. Here' we report a panel of new soft single molecule polymer nanomaterials (SMPNs) with varying circulation times in mice (t1/2ß ~ 22 to 65 h) and use proteomics to probe protein corona at the nano-biointerface to elucidate the mechanism of blood residency of nanomaterials. The composition of the protein opsonins on SMPNs is qualitatively and quantitatively dynamic with time in circulation. SMPNs that circulate longer are able to clear some of the initial surface-bound common opsonins, including immunoglobulins, complement, and coagulation proteins. This continuous remodelling of protein opsonins may be an important decisive step in directing elimination or residence of soft nanomaterials in vivo.

Coverage with dosimetric concordance index (CDCI): a tool for evaluating dosimetric impact of inter-observer target variability in brachytherapy.

PURPOSE: The aim of this study was to propose an index for evaluating dosimetric impact of inter-observer target delineation variability in brachytherapy. MATERIAL AND METHODS: The coverage with dosimetric concordance index (CDCI) is expressed as CDCIcommon and CDCIpair. The CDCIcommon is the mean coverage of target volume with common volume irradiated by prescription dose among all observers and represents the condition of worst target coverage. CDCIpair is the generalized form of CDCI, which is mean target coverage with common prescription volume obtained between all possible pairs of observers and represents more realistic coverage of target with dosimetric concordance. The index was used to evaluate the dosimetric impact of target delineation variability in optimized conformal plans on target volumes of five radiation oncologists for twenty patients of multi-catheter interstitial partial breast brachytherapy. RESULTS: The mean decline of 5.6 ±3.2% and 11.3 ±5.7% in CDCIpair and CDCIcommon, respectively, was observed comparing to coverage index (CI) of target volume in all patients due to inter-observer target variability. CDCIcommon and CDCIpair were found to have significant linear correlation (r = 0.964, p < 0.000). The difference between CDC and CI increased with the mean relative target volume among observers. Significant correlation (r = 0.962, p < 0.000) was also noted for the difference (Δ) in CDCIcommon and CDCIpair with CI of target volume. CONCLUSIONS: The recommended indices and difference between the dosimetric coverage of target volume (CI) with CDCI (ΔCDCI) can be used for evaluating dosimetric impact of the inter-observer target delineation variability.

Can subcentimetre ultrasound detected angiomyolipomas be safely disregarded?

AIM: To optimise follow-up by dismissing lesions on baseline ultrasound (US) if renal lesions conform to US criteria of an angiomyolipoma (AML). METHOD AND MATERIALS: The present study was a 10-year retrospective review of patients who were found to have incidental hyperechoic renal lesions on US to ascertain the outcome from subsequent imaging, clinical encounters, and cancer registrations. Exclusions included renal calculi, tuberous sclerosis, Von-Hippel-Lindau, or a known cancer. RESULTS: After excluding 39 patients, 1,493 patients were identified. One hundred and sixty had more than one lesion with 87 patients having bilateral lesions. Regardless of indication, 889 patients had subsequent imaging within 5 years (59.5%). The average size of all AMLs was 13.2 mm. In the group with lesions that were <10 mm (807), 438 had imaging follow-up with an average follow-up time of 1.5 years. Mean lesion size in this group was 7 mm, with an average increase of <0.5 mm on follow-up. No lesions were found to be malignant on subsequent imaging nor did any of these patients have a subsequent renal cancer diagnosis registered at local multidisciplinary team meetings. CONCLUSION: No incidental subcentimetre hyperechoic renal lesion with imaging characteristics of an AML demonstrated significant growth or developed into a malignancy on follow-up.

Checkrein Deformity of the Great toe Managed by Midfoot Flexor Hallucis Longus Z-Plasty: A Case Report.

INTRODUCTION: Checkrein deformities are rare and involve entrapment or fixed tethering of the flexor hallucis longus (FHL) tendon. CASE REPORT: We present the case of a 25-year-old male who presented with complaint of clawing of his great toe. A history of previous open reduction internal fixation for distal tibia fracture was described 3 years back. Exploration of FHL tendons was performed at the level of the midfoot. Correction was achieved after z-plasty of FHL tendon. This case highlights another late complication of distal tibial fracture which should be actively looked for in patients with this injury. We describe the ease of surgical correction through an operative field free of scar tissue as compared to classical method of operating near fracture site and releasing adhesions of muscle belly. CONCLUSION: We suggest that exploration at the midfoot should be the primary surgical intervention in similar cases of checkrein deformity.