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A cascade inter–intramolecular double Michael strategy for the synthesis of highly functionalized cyclohexanones from curcumins and arylidenemalonates is reported. This strategy works in the presence of aqueous KOH using TBAB as a suitable phase transfer catalyst at room temperature. The functionalized cyclohexanones are formed as major products in moderate to excellent yields with complete diastereoselectivity in most cases. A triple Michael adduct, tetrahydrochromen-4-one, is also formed as a side product in a few cases with excellent diastereoselectivity.

Abstract Background Surgery and radiotherapy are well-established standards of care for unilateral stage 0 and I early-stage glottic cancer (ESGC). Based on comparative studies and meta-analyses, functional and oncological outcomes after both treatment modalities are similar. Historically, radiotherapy (RT) has been performed by irradiation of the whole larynx. However, only the involved vocal cord is being treated with recently introduced hypofractionated concepts that result in 8 to 10-fold smaller target volumes. Retrospective data argues for an improvement in voice quality with non-inferior local control. Based on these findings, single vocal cord irradiation (SVCI) has been implemented as a routine approach in some institutions for ESGC in recent years. However, prospective data directly comparing SVCI with surgery is lacking. The aim of VoiceS is to fill this gap. Methods In this prospective randomized multi-center open-label phase III study with a superiority design, 34 patients with histopathologically confirmed, untreated, unilateral stage 0-I ESGC (unilateral cTis or cT1a) will be randomized to SVCI or transoral CO2-laser microsurgical cordectomy (TLM). Average difference in voice quality, measured by using the voice handicap index (VHI) will be modeled over four time points (6, 12, 18, and 24 months). Primary endpoint of this study will be the patient-reported subjective voice quality between 6 to 24 months after randomization. Secondary endpoints will include perceptual impression of the voice via roughness – breathiness – hoarseness (RBH) assessment at the above-mentioned time points. Additionally, quantitative characteristics of voice, loco-regional tumor control at 2 and 5 years, and treatment toxicity at 2 and 5 years based on CTCAE v.5.0 will be reported. Discussion To our knowledge, VoiceS is the first randomized phase III trial comparing SVCI with TLM. Results of this study may lead to improved decision-making in the treatment of ESGC. Trial registration ClinicalTrials.gov NCT04057209. Registered on 15 August 2019. Cantonal Ethics Committee KEK-BE 2019-01506

Context Tumors of parapharyngeal space (PPS) are rare and histologically diverse. The management of these tumors requires diligent assessment and planning with due consideration of various anatomical and pathological aspects of the lesion. Aims This retrospective study aims to present our experiences in the clinical and pathological aspects of PPS tumors with a critical evaluation of management. Settings and Design Retrospective analytical study. Methods and Material The electronic medical records of 60 cases of PPS tumors, managed surgically from 2007 to 2017, were reviewed and analyzed using SPSS 22 software. The mean follow-up duration was 44 months. Results The mean age was 45 years with a male-to-female ratio of 1.7 (38:22). The majority of the tumors were benign (71.7%) and the most common presentation being upper neck mass or oropharyngeal mass. Histologically, neurogenic tumors were most common (43.3%) PPS tumors, followed by tumors of salivary gland origin. Magnetic resonance imaging was used as a diagnostic modality in 70% of cases, and computed tomography scan and positron emission tomography/CT were used in 26.7 and 3.3% of cases, respectively. In our study, the diagnostic accuracy of fine-needle aspiration cytology was 71% for benign and 47% for malignant lesions. The most common approach for surgery used was transcervical (72%). Conclusion The study reveals that cranial nerve palsy is the most common complication associated with PPS tumors. Completely resected, malignant tumors originating within PPS have a good prognosis, as compared with tumors extending or metastasized to PPS.

IntroductionGender discrimination (GD) though rarely blatant, may present indirectly within a surgical department in the form of subtle inequities, differing standards, and bias. GD encompasses a wide spectrum including academic development, surgical opportunities and sexual harassment.MethodsWe conducted an online survey to analyse the perceived incidence of GD in the surgical oncology department at a tertiary care cancer centre in India. The questionnaire consisted of 15 questions and was mailed to the entire department including trainees and faculty. Anonymity was maintained while collecting the data only of the participants' gender and whether they were faculty or trainee. Collated responses were analysed using proportions.ResultsThe questionnaire was sent out to 200 recipients of whom 56% (112/200) responded via an online survey. Respondents included 84% of faculty (42/50) and 46.6% of trainees (70/150). GD was perceived by 28% of female trainees (7/25) as compared to 6.6% of male trainees (3/45), whereas amongst faculty, GD was perceived by 26.6% of female faculty (4/15) compared to 14.8% of male faculty (3/27). Approximately 13% of our trainees and 12% of our faculty mentioned that GD affected their professional performance or mental well-being. GD was experienced in terms of work experience and opportunities by a majority of trainees (13%) and faculty (9.5%). There was a significant lack of awareness about recourse to an institutional grievance committee by trainees (47%) compared to faculty (14%). About 7% of trainees and 12% of faculty acknowledged that they may have been responsible for intentional/unintentional GD.ConclusionGender discrimination can present in subtle or overt fashion in surgical departments and requires active sustained efforts to allow both genders to feel equally empowered. Establishing a system to objectively evaluate gender equity while avoiding stereotyping for certain roles can help minimize GD.

Background: Early thyroid cancers have excellent long-term outcomes, yet the word “cancer” draws unnecessary apprehension. This study aimed to define when the recommendations for observation and surveillance may be extended to early thyroid cancers at the population level. Methods: Non-metastasized thyroid cancers ≤40 mm diameter were identified from the 1975–2016 Surveillance, Epidemiology and End Results (SEER) database. Causes of death were compared across demographic data. Disease-specific outcomes were compared to the age-adjusted healthy United States (US) population. Survival estimates were computed using Kaplan–Meier and compared using the Cox proportional hazard model. Dynamic benchmarks impacting disease-specific overall survival were determined by decision tree modeling and tested by the Cox model. Results: Of the 28,728 thyroid cancers included in this study, 98.4% underwent some form of thyroid-specific treatment and were followed for a maximum of 10.9 years. This group had a 4.3% mortality rate at the end of follow-up (10.9 years maximum), with 13 times more deaths attributed to competing risks rather than thyroid cancer (stage T1a versus stage T1b, P=1.000; T1 versus T2, P26 mm impacted outcomes. Conclusion: Based on the current data, T1a and T1b nodules have similar survival outcomes and are not significantly impacted even when left untreated. Multi-institutional prospective studies are needed to confirm these findings so that current observation and surveillance recommendations can be extended to certain T1 thyroid nodules.

Objective: To evaluate the survival outcomes for a cohort of nasopharyngeal cancer with intracranial extension (ICE) treated with induction chemotherapy (ICT) followed by chemo-intensity-modulated radiotherapy (CTRT) at a tertiary cancer center. Methods: We retrospectively analyzed 45 patients with histologically proven, non-metastatic NPC with ICE treated at our institute between October 2008 and October 2016. Patients were classified as minor ICE or major ICE, based on the extent of ICE. All the patients received 2–3 cycles of a taxane-based ICT regimen followed by CTRT. Radiotherapy was delivered with “risk-adapted” intensity-modulated radiotherapy (IMRT) technique in all patients. Results: After a median follow up of 45 months (range: 8–113 months), the estimated 5-year DFS, LRFS, DMFS, and OS of the entire cohort was 58%, 82%, 67% and 74% respectively. On multivariate analysis, histological subtype was an independent predictor of LRFS, and age was an independent predictor of DFS. The extent of ICE showed only a trend towards worse DFS (P = 0.06). None of the factors significantly predicted for DMFS or OS. Gender, N-stage, and response to ICT did not significantly affect any of the outcomes. Grade 2 or worse subcutaneous fibrosis was seen in 22% of patients and grade 2 or worse xerostomia was seen in 24% of patients at last follow up. Thirty-three percent of the patients developed clinical hypothyroidism at last follow up. None of the patients experienced any neurological or vascular complications. Conclusions: Taxane-based induction chemotherapy followed by chemo-intensity modulated radiotherapy resulted in excellent locoregional control and survival with acceptable toxicities in patients of nasopharyngeal cancer with intracranial extension. Distant metastasis continues to be the predominant problem in these patients.

Bacground: Surgical margin is an important prognostic factor for oral cancers (oral squamous cell carcinoma [OSCC]). The correlation of margin with the type of reconstruction has never been studied. Aim: This study aimed to correlate surgical margins with the type of reconstruction. Methods: This was a retrospective study of 410 treatment-naïve OSCC patients. As per the methods of reconstruction, three groups were made when reconstruction was performed using pedicled flap (PF) or local flap, free flap, and primary closure (PC). Statistical Analysis: Chi-square test was used for comparison of margin status as per the method of reconstruction. Mann–Whitney test was used to find the difference between the mean margin width with respect to the type of reconstruction. Results: The overall incidence of close/positive margins was 7.8%. The incidence of close/positive margins was not significantly different in free flap group compared to PF (P = 0.06) or PC (P = 0.835) group. However, there was a significant difference in the incidence of close/positive margins between PC and PF groups (P = 0.021). Whether the reconstruction is performed by the primary surgeon or by a another surgeon, it did not have an impact on adequacy of margins (P = 0.334). Margins were wider when the reconstruction is performed by a different team (P = 0.015) or when reconstruction is performed as compared to PC. Conclusion: Margins are not affected by the type of reconstruction (pedicled vs. free flap) and the team doing reconstruction (same vs. another team). Margins are significantly compromised when a surgeon performs PC himself/herself compared to PF.

The coronavirus disease-19 pandemic has affected all aspects of health care including clinical research, as the focus of health-care systems has shifted to maintaining essential care. The impact on clinical research has been profound. In this article, we have enlisted the multiple challenges faced by investigators and sites in carrying out clinical research activities during this crisis and the steps which can be taken by them to reduce the impact of this evolving pandemic on clinical research.

Background: Sinonasal tumors are a rare group of neoplasms with limited data available regarding their treatment. Objectives: To estimate the 5 year outcomes and late adverse events of locally advanced sinonasal tumors treated with neoadjuvant therapy (NACT) followed by local therapy. Methods: Twenty-five patients with locally advanced esthesioneuroblastoma or sinonasal neuroendocrine tumors treated between August 2010 and August 2014 with NACT followed by local therapy were selected. The 5-year outcome and late adverse events (CTCAE version 4.02) were noted. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. COX regression analysis was used to identify factors impacting PFS and OS. Results: The median follow-up was 5.15 years. The 5-year PFS in the esthesioneuroblastoma cohort and in the sinonasal neuroendocrine carcinoma (SNEC) cohort was 63.5% (95% confidence interval [CI]: 28.9–84.7) and 34.6% (95% CI: 10.1–61.1), respectively (P = 0.1). The only factor impacting PFS on multivariate analysis was a response to NACT (P = 0.033). The 5-year OS in the esthesioneuroblastoma cohort and in the SNEC cohort was 91.7% (95% CI: 53.9–98.9) and 46.2% (95% CI: 19.2–69.6), respectively (P = 0.024). Any grade late adverse events were seen in 20 patients (80%). Metabolic late adverse events were seen in 19 patients (76%). Conclusion: NACT in advanced sinonasal cancers is associated with an improvement in 5-year outcomes. However, late side effects, especially metabolic, are seen in these patients and should be evaluated during follow-up.

Objectives: The purpose of the study was to report a case series of ameloblastoma treated by radical approach with a negative margin. Study Design: The clinical, demographic, and the histopathological data of 24 biopsy-proven ameloblastoma were obtained and analyzed retrospectively from the electronic medical records. Statistical analysis was done using the software SPSS 20.0. Disease-free survival was calculated using Kaplan–Meier analysis. Results: The mean age of the patients in the study group was 46.6 (range, 17–69) years with male to female ratio of 1.18:1. The most common site of origin was mandible (75%). There was a significant positive linear correlation between size and age of the patients with a correlation coefficient of 0.85 (P = 0.042). Patients having multicystic ameloblastoma had a significantly higher age of presentation and larger size than unicystic ameloblastoma (P < 0.05). The mean distance of the closest mucosal/bony cut margin from the lesion was 6 mm (range 1–45 mm). All patients were alive, and 95.8% of the patients were disease free at a mean follow-up of 48 months. Conclusion: We recommend appropriate radical treatment for most of the patients of ameloblastoma with a negative margin except for small unicystic ameloblastoma. Thus, it is time to revisit the concept of conservative procedures in the management of ameloblastoma.

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The human peripheral leukocyte subset composition depends on genotype variation and pre-natal and post-natal environmental influence diversity. We quantified this composition in adults and neonates, and compared the median values and dispersal ranges of various subsets in them. We confirmed higher frequencies of monocytes and regulatory T cells (Tregs), similar frequencies of neutrophils, and lower frequencies of CD8 T cells, NKT cells, B1 B cells and gamma-delta T cells in neonatal umbilical cord blood. Unlike previous reports, we found higher frequencies of eosinophils and B cells, higher CD4:CD8 ratios, lower frequencies of T cells and iNKT cells, and similar frequencies of CD4 T cells and NK cells in neonates. We characterized monocyte subsets and dendritic cell (DC) subsets in far greater detail than previously reported, using recently described surface markers and gating strategies and observed that neonates had lower frequencies of patrolling monocytes and lower myeloid dendritic cell (mDC):plasmacytoid DC (pDC) ratios. Our data contribute to South Asian reference values for these parameters. We found that dispersal ranges differ between different leukocyte subsets, suggesting differential determination of variation. Further, some subsets were more dispersed in adults than in neonates suggesting influences of postnatal sources of variation, while some show the opposite pattern suggesting influences of developmental process variation. Together, these data and analyses provide interesting biological possibilities for future exploration.

Purpose: The present study was undertaken to assess the level of awareness on legislations relating to intellectual disability among family members in India.Method: A sample of 103 respondents attending home based training services for their wards at National Institute for the Mentally Handicapped (NIMH), India, were administered a thirty item questionnaire, classified into awareness of legislations, awareness of rights, concessions and benefits and life cycle needs.Results: There is a moderate level of awareness on legislative aspects. Educated respondents showed better awareness about legislations than less educated persons. Respondents were better aware of benefits and concessions because of their direct utility in their day-to-day activities.Conclusion: There is a need for creation of awareness and sensitization among parents and caregivers having persons with intellectual disability to enable them to receive optimum benefits. To reach the uneducated population the materials must also be made available in non-print media such as television, posters and illustrated pamphlets.

While infections are a major cause of neonatal mortality in India even in full-term neonates, this is an especial problem in the large proportion (~20%) of neonates born underweight (or small-for-gestational-age; SGA). One potential contributory factor for this susceptibility is the possibility that immune system maturation may be affected along with intrauterine growth retardation.In order to examine the possibility that differences in immune status may underlie the susceptibility of SGA neonates to infections, we enumerated the frequencies and concentrations of 22 leukocyte subset populations as well as IgM and IgA levels in umbilical cord blood from full-term SGA neonates and compared them with values from normal-weight (or appropriate-for-gestational-age; AGA) full-term neonates. We eliminated most SGA-associated risk factors in the exclusion criteria so as to ensure that AGA-SGA differences, if any, would be more likely to be associated with the underweight status itself.An analysis of 502 such samples, including 50 from SGA neonates, showed that SGA neonates have significantly fewer plasmacytoid dendritic cells (pDCs), a higher myeloid DC (mDC) to pDC ratio, more natural killer (NK) cells, and higher IgM levels in cord blood in comparison with AGA neonates. Other differences were also observed such as tendencies to lower CD4:CD8 ratios and greater prominence of inflammatory monocytes, mDCs and neutrophils, but while some of them had substantial differences, they did not quite reach the standard level of statistical significance.These differences in cellular lineages of the immune system possibly reflect stress responses in utero associated with growth restriction. Increased susceptibility to infections may thus be linked to complex immune system dysregulation rather than simply retarded immune system maturation.

Ameloblastoma is a unique, histologically benign but aggressive neoplasm of the jaws, arising from odontogenic epithelium with potency to cause extensive destruction of jaw bones and infiltration into the surrounding tissues. Recurrences are common after incomplete treatment. Recurrences can occur at difficult sites such as temporal and infratemporal fossa, orbit, anterior cranial base, paranasal sinuses etc. Fine needle aspiration cytology or core biopsy of these recurrent lesions may be misleading. Clinical course and radiological features help immensely in these situations. Good communication between surgeon, radiologist, and pathologist is of paramount importance.

PURPOSE: To evaluate the prevalence of pterygia and associated factors in a rural population in a mostly undeveloped agrarian region. METHODS: The Central India Eye and Medical Study is a population-based study performed in a rural region of Central India. The study comprised 4711 subjects (aged 30+ years). A detailed ophthalmic and medical examination was performed. A pterygium was diagnosed during the slit lamp examination and confirmed on corneal photographs. It was defined as a fleshy fibrovascular growth, crossing the limbus and typically seen on the nasal, and sometimes temporal, conjunctiva. RESULTS: A pterygium was detected in 798 eyes (prevalence rate: 8.47 ± 0.29%) of 608 (12.91 ± 0.49%) subjects. Bilateral pterygia were present in 190 subjects (4.0% of study population). Pterygia prevalence increased from 6.7 ± 0.8% in the age group 30-39 years, to 13.5 ± 1.2% in the age group 50-59 years, to 25.3 ± 2.1% in the age group 70-79 years. Prevalence of pterygia was associated with older age (P

Japanese encephalitis virus (JEV) is a neurotropic flavivirus, which causes viral encephalitis leading to death in about 20-30% of severely-infected people. Although JEV is known to be a neurotropic virus its replication in non-neuronal cells in peripheral tissues is likely to play a key role in viral dissemination and pathogenesis. We have investigated the effect of JEV infection on cellular junctions in a number of non-neuronal cells. We show that JEV affects the permeability barrier functions in polarized epithelial cells at later stages of infection. The levels of some of the tight and adherens junction proteins were reduced in epithelial and endothelial cells and also in hepatocytes. Despite the induction of antiviral response, barrier disruption was not mediated by secreted factors from the infected cells. Localization of tight junction protein claudin-1 was severely perturbed in JEV-infected cells and claudin-1 partially colocalized with JEV in intracellular compartments and targeted for lysosomal degradation. Expression of JEV-capsid alone significantly affected the permeability barrier functions in these cells. Our results suggest that JEV infection modulates cellular junctions in non-neuronal cells and compromises the permeability barrier of epithelial and endothelial cells which may play a role in viral dissemination in peripheral tissues.

The current study aimed to investigate the drug delivery potential of chitosan‐conjugated Spondias pinnata phytocompounds for anticancer and antibacterial applications. The phytochemical composition of the aqueous extract of S. pinnata plant leaves revealed seven major compounds, including stearic acid, 2H‐Indol‐2‐one, beta amyrin, oleic acid, octadecanoic acid, 7‐hexadecenoic acid, and phytol. Additionally, five minor compounds were identified through GC–MS analysis. SEM analysis of chitosan‐conjugated S. pinnata phytocompounds revealed amorphous particles. This demonstrates the attainment of optimized larger crystallites, which differ in size and shape extensively. The antioxidant potential of both the chitosan‐conjugated S. pinnata phytocompounds and S. pinnata leaf extracts was evaluated via DPPH and ABTS assays, and the results revealed that the chitosan‐conjugated S. pinnata phytocompounds exhibited significant scavenging activity, with IC50 values of 18.20 and 33.15 μg/mL, respectively. Chitosan‐conjugated S. pinnata phytocompounds also demonstrated antibacterial activity against four clinically significant infections, with zones of inhibition ranging from 16 ± 0.07, 19 ± 0.10, 17 ± 0.09, and 19 ± 0.11 mm against Escherichia coli (MTCC 452), Salmonella typhi (MTCC 733), Klebsiella pneumonia (MTCC 39), and Pseudomonas aeruginosa (MTCC 1688), respectively. Furthermore, the cytotoxicity of the chitosan‐conjugated S. pinnata phytocompounds was assessed against A549 lung cancer cells, and the results revealed a significant reduction in cell viability (33.85) at higher concentrations of 150 μg/mL. The IC50 values of S. pinnata leaf extract (149.2 mg/mL) and chitosan‐conjugated S. pinnata (126.4 mg/mL) toward A549 lung cancer cells were recorded. Overall, the results of the present study highlight the therapeutic applications of chitosan‐conjugated S. pinnata phytocompounds, particularly in the context of their anticancer and antibacterial activities. [ABSTRACT FROM AUTHOR]