A Comparison of the Toxicities in Patients With Locally Advanced Head and Neck Cancers Treated With Concomitant Boost Radiotherapy Versus Conventional Chemoradiation.

PURPOSE: To compare the objective and patient-reported toxicities of concomitant boost radiotherapy (CBRT) and concurrent chemoradiation (CRT) in patients with locally advanced head and neck cancers. METHODS AND MATERIAL: In this prospective study, 46 patients with histologically proven stage III-IVA head and neck cancer were randomly assigned to receive either concurrent chemoradiation to a dose of 66 Gy in 33 fractions over 6.5 weeks with concurrent cisplatin (40 mg/m2 IV weekly; control arm) or accelerated radiotherapy with concomitant boost radiotherapy (study arm) to a dose of 67.5 Gy in 40 fractions in five weeks. Acute toxicity was evaluated using RTOG toxicity criteria. The assessment was done weekly after initiation of treatment, at the first follow-up (six weeks), and at three months. The four main patient-reported symptoms of pain, hoarseness of voice, dryness of mouth, and loss of taste were also compared between the two groups to assess patient quality of life during treatment. RESULTS: The mean treatment duration was 37 days in the CBRT arm and 49 days in the CRT arm. Treatment-related interruptions were less in the study group,17.3% in the study, and 27.2% in the control with insignificant P-value. Grade III laryngeal toxicity was significantly higher in the study group (P=0.029). Other acute grade I-III toxicities (pharyngeal, skin, mucositis, and salivary) were comparable in both CRT and CBRT arms. Grade IV toxicities were seen only in the CBRT arm but were resolved at the first follow-up. Haematological toxicities and renal toxicities were significantly higher in the CRT arm, with significant P-values of 0.0004 and 0.018, respectively. CONCLUSION: In patients with locally advanced head and neck cancer, concomitant boost radiotherapy is well tolerated with acceptable local toxicity and minimal systemic toxicity as compared to conventional chemoradiation. It is a feasible option for patients with locally advanced head and neck cancer not fit for concurrent chemoradiation.

A comparison of dosimetric parameters in high-dose-rate intracavitary brachytherapy using tandem and ring applicators: is the combination of a rectal retractor and radio-opaque vaginal packing better than rectal retractor alone for rectum sparing in cervical cancer?

Purpose: To describe a novel packing technique of combining radio-opaque vaginal packing (VP) with rectal retractor (RR) blade to displace rectum and to compare the standard International Commission on Radiation Units & Measurements-38 (ICRU-38) rectal, bladder point doses and volume parameters with the conventional technique of using RR alone with tandem and ring (T&R) applicators in high-dose-rate (HDR) intracavitary brachytherapy (ICB) for cervical cancer. Materials and methods: A retrospective analysis of the treatment plans of a cohort of 24 consecutively treated patients with locally advanced cervical cancer was performed. All patients received external beam radiotherapy with a dose of 45-50.4 Gy, in fractions of 1.8-2 Gy, to the whole pelvis with concurrent weekly chemotherapy, followed by HDR-ICB. The treatment plans for each brachytherapy session using T&R applicators that these patients received were included for analysis. A total of 17 treatment plans in which the combination of RR and radio-opaque VP was used for rectum separation were included in the combination (RR+VP) group, and 21 treatment plans in which a RR alone was used were included in the conventional (RR) group. Results: The mean dose to the ICRU rectal point was 39.7% of the point A dose (range, 28.8%-50.4%; median 38.6%) in the RR+VP group and 52.7% (range, 46.9%-63.6%; median 51.7%) in the RR group. This 13% reduction in the mean dose to the ICRU rectal point was statistically significant (p = 0.001). The mean dose to the ICRU bladder point was 55.4% of the point A dose (range, 26.3%-73.6%; median 57.4%) in the RR+VP group and 45.3% (range, 23.7%-72.7%; median 46.9%) in the RR group. This 10.1% increase in the mean dose to the ICRU bladder point was also significant (p = 0.024). The other point dose and volume parameters were similar between groups. Conclusion: Compared to the conventional use of a RR blade alone for rectum separation, combining a RR blade with radio-opaque VP significantly reduced the ICRU rectal point dose.

Porphyromonas gingivalis resistance and virulence: An integrated functional network analysis.

BACKGROUND: The gram-negative bacteria Porphyromonas gingivalis (PG) is the most prevalent cause of periodontal diseases and multidrug-resistant (MDR) infections. Periodontitis and MDR infections are severe due to PG's ability to efflux antimicrobial and virulence factors. This gives rise to colonisation, biofilm development, evasion, and modulation of the host defence system. Despite extensive studies on the MDR efflux pump in other pathogens, little is known about the efflux pump and its association with the virulence factor in PG. Prolonged infection of PG leads to complete loss of teeth and other systemic diseases. This necessitates the development of new therapeutic interventions to prevent and control MDR. OBJECTIVE: The study aims to identify the most indispensable proteins that regulate both resistance and virulence in PG, which could therefore be used as a target to fight against the MDR threat to antibiotics. METHODS: We have adopted a hierarchical network-based approach to construct a protein interaction network. Firstly, individual networks of four major efflux pump proteins and two virulence regulatory proteins were constructed, followed by integrating them into one. The relationship between proteins was investigated using a combination of centrality scores, k-core network decomposition, and functional annotation, to computationally identify the indispensable proteins. RESULTS: Our study identified four topologically significant genes, PG_0538, PG_0539, PG_0285, and PG_1797, as potential pharmacological targets. PG_0539 and PG_1797 were identified to have significant associations between the efflux pump and virulence genes. This type of underpinning research may help in narrowing the drug spectrum used for treating periodontal diseases, and may also be exploited to look into antibiotic resistance and pathogenicity in bacteria other than PG.

A Prospective Observational Study Comparing Long-Course Conventional Neoadjuvant Chemoradiotherapy with Short-Course Radiotherapy Followed by Consolidation Chemotherapy with Delayed Surgery in Locally Advanced Rectal Cancer.

Background Polish and Australian randomized studies compared short-course radiotherapy (RT) with immediate surgery and long-course chemoradiotherapy (CRT) with delayed surgery. In these studies, similar long-term survival and local control have been reported for both these approaches, but pathological complete response (pCR) is not better with short-course RT. Moreover, studies have shown better tumor downstaging with delayed surgery. In this context, the use of short-course RT with delayed surgery may have some advantages and needs to be tested in clinical trials. Patients and Methods This was a two-arm, prospective, observational study, in which preoperative short-course RT followed by two cycles of chemotherapy was compared with the conventional neoadjuvant CRT in locally advanced rectal cancer. The primary end points were the rate of complete response and toxicity profile. The secondary end points were the rate of R0 resection, overall survival, and progression-free survival. The data obtained from the two arms were analyzed using Pearson's chi-square test to determine the statistical significance between the two treatment arms. Results The pCR rate was 6.7% in the study arm and 0 in the control arm ( p = 0.343). The RO resection rates were 92.8 and 92.3% in the study and control arms, respectively. The rates of grade 3and 4 acute toxicity in the study and control arms were 14.2 and 61.5%, respectively ( p = 0.011). The rates of grade 3 and 4 late toxicity in the study and control arms were 21.4 and 15.3%, respectively ( p = 0.686). Conclusions The pCR rates and the late toxicities in both arms are comparable. The major advantages of the 5 × 5 Gy regimen with chemotherapy in a neoadjuvant setting are a significant reduction in acute toxicities and better patient compliance along with similar efficacy as that of the standard regimen.

Four percent formalin application for the management of radiation proctitis in carcinoma cervix patients: An effective, safe, and economical practice.

CONTEXT: Radiotherapy is a very effective treatment modality for pelvic malignancies such as carcinoma of the cervix. However, it is quite common for chronic radiation proctitis (CRP) to manifest after radical radiotherapy. CRP is a source of significant morbidity, and there is a lack of effective treatment modalities. There also exists a general lack of guidelines on management of CRP. AIMS: To assess the benefit from 4% formalin application for the treatment of Grade >2 CRP among patients previously treated with radical radiotherapy for cervical carcinoma. SETTINGS AND DESIGN: This retrospective descriptive study involved 29 eligible patients who were treated from November 2010 - November 2015 for CRP with 4% formalin application. MATERIALS AND METHODS: Of the 1864 patients of carcinoma cervix treated during the said patients, 29 patients fulfilled the eligibility criteria. Eligible patients were invited telephonically for follow-up and were assessed for response and complications of the procedure. RESULTS: The treatment of hemorrhagic radiation proctitis with local formalin instillation is effective, well tolerated and safe procedure. The procedure is inexpensive, technically simple and can be done on an outpatient basis. 62% patients had complete freedom from rectal bleed, while 34.5% patients had partial benefit. Only one patient required diversion colostomy for persistent bleeding.

Prospective randomized trial to compare the outcome and tolerability of delivering the same total dose of radiation in 61/2 weeks versus 51/2 weeks time in head and neck cancers.

BACKGROUND: Concurrent chemoradiation is currently considered to be the standard of care in the treatment of head and neck cancer. In developing countries like ours, a good number of patients cannot tolerate chemoradiation because of the poor general condition and financial constraints. Those patients are treated with radiation alone. The optimum radiotherapy (RT) schedule for best local control and acceptable toxicity is not yet clear. We aimed to find out whether shortening of treatment time using six instead of five RT fractions per week improves the locoregional control in squamous cell carcinoma of head and neck. MATERIALS AND METHODS: We conducted a prospective randomized study for a period of 2 years from September 2007 to August 2009 in 109 untreated patients of squamous cell carcinoma of head and neck with histologically confirmed diagnosis and no evidence of distant metastasis. Study group (55 patients) received accelerated RT with 6 fractions per week (66 Gy/33#/51/2 weeks). Control group (54 patients) received conventional RT with 5 fractions per week (66 Gy/33#/61/2 weeks). Tumor control, survival, acute and late toxicities were assessed. RESULTS: At a median follow-up of 43 months, 29 patients (52.7%) in the 6 fractions group and 24 patients (44.4%) in the 5 fractions group were disease-free (P = 0.852). The benefit of shortening was higher for advanced disease control though it was not statistically significant. Grade 3 and 4 skin toxicity was significantly higher in the accelerated RT (70.9%) arm as compared to conventional (35.1%) arm (P = 0.04). Grade 3 mucositis was significantly higher in the accelerated RT arm (32.7% vs. 16.6%; P = 0.041). Those acute toxicities were managed conservatively. There was no difference in late toxicities between the two arms. CONCLUSION: Use of 6 fractions per week instead of 5 fractions per week is feasible, tolerable, and results in a better outcome in the patients of head and neck cancers.

Synthesis of well-dispersed silver nanorods of different aspect ratios and their antimicrobial properties against Gram positive and negative bacterial strains.

In the present contribution, we describe the synthesis of highly dispersed silver nanorods (NRs) of different aspect ratios using a chemical route. The shape and size of the synthesized NRs were characterized by Transmission Electron Microscopy (TEM) and UV-visible spectroscopy. Longitudinal and transverse absorptions bands confirm the rod type structure. The experimentally recorded UV-visible spectra of NRs solutions were fitted by using an expression of the extinction coefficient for rod like nano structures under the dipole approximation. Simulated and experimentally observed UV-visible spectra were compared to determine the aspect ratios (R) of NRs. The average values of R for NR1, NR2 and NR3 solutions are estimated to be 3.0 ± 0.1, 1.8 ± 0.1 and 1.2 ± 0.1, respectively. These values are in good agreement with those obtained by TEM micrographs. The silver NRs of known aspect ratios are used to study antimicrobial activities against B. subtilis (gram positive) and E. coli (gram negative) microbes. We observed that the NRs of intermediate aspect ratio (R = 1.8) have greater antimicrobial effect against both, B. subtilis (gram positive) and E. coli (gram negative). The NRs of aspect ratio, R = 3.0 has better antimicrobial activities against gram positive than on the gram negative.

Use of artificial neural network (ANN) for the development of bioprocess using Pinus roxburghii fallen foliages for the release of polyphenols and reducing sugars.

In present study, different parameters, i.e., percentage of NaOH, loading volume, microwave power (watt) and volume of water during pretreatment were optimized by ANN for release of polyphenols and sugars from pine fallen foliage. ANN used was feed forward back propagation type with 72 input, 72 output and 10 hidden layers coupled with Lvenberg-Marquardt (LM) training algorithms. The predicted optimal values by generated neural network for alkali pretreatment were 6 ml (0.5% NaOH)/g of substrate, soaking time of 10 min followed by 1 min of 100 W microwave. Pretreated sample on enzymatic hydrolysis at 50°C for 20 h with cocktail of cellulase, xylanase and laccase produced by locally isolated consortia released 668.9 mg/g of total sugar and 265.06 mg/g of total polyphenols. Optimization by ANN showed good yield, therefore, indicating its suitability for bioprocess modeling and control for release of reducing sugars and polyphenols from pine foliage.

Knowledge of risk factors and early detection methods and practices towards breast cancer among nurses in Indira Gandhi Medical College, Shimla, Himachal Pradesh, India.

BACKGROUND: Breast cancer is an increasing health problem in India. Screening for early detection should lead to a reduction in mortality from the disease. It is known that motivation by nurses influences uptake of screening methods by women. This study aimed to investigate knowledge of breast cancer risk factors and early detection methods and the practice of screening among nurses in Indira Gandhi Medical College, Shimla, Himachal Pradesh. MATERIALS AND METHODS: A cross-sectional study was conducted using a self-administered questionnaire to assess the knowledge of breast cancer risk factors, early detection methods and practice of screening methods among 457 nurses working in an Indira Gandhi Medical College, Shimla-H.P. Chi square test, Data was analysed using SPSS version 16. Test of significance used was chi square test. RESULTS: The response rate of the study was 94.9%. The average knowledge of risk factors about breast cancer of the entire population is 49%. 10.5% of nurses had poor knowledge, 25.2% of the nurses had good knowledge, 45% had very good knowledge and 16.3% of the nurses had excellent knowledge about risk factors of breast cancer and early detection methods. The knowledge level was significantly higher among BSC nurses than nurses with Diploma. 54% of participants in this study reportedly practice BSE at least once every year. Less than one-third reported that they had CBE within the past one year. 7% ever had mammogram before this study. CONCLUSIONS: Results from this study suggest the frequent continuing medical education programmes on breast cancer at institutional level is desirable.

Mathematical model-based optimization of physico-enzymatic hydrolysis of Pinus roxburghii needles for the production of reducing sugars.

The objective of this study was to optimize the physico-enzymatic pretreatment of P. roxburghii fallen foliage (needles) to produce reducing sugars through response surface methodology (RSM) with central composite face centered design (CCD). Under this, five parameters, i.e., concentration of laccase, cellulose and xylanase, steam explosion pressure and incubation period, at three levels with twenty six runs were taken into account. Cellulase, xylanase and laccase enzymes with activity 4.563, 38.32 and 0.05 IU/mL, respectively, were produced from locally isolated microbial strains. The analysis of variance (ANOVA) was applied for the validation of the predicted model at 95% of confidence level. This model predicted 334 mg/g release of reducing sugars on treating P. roxburghii fallen foliage with 1.18 mL of cellulose, 0.31 mL of xylanase and 0.01 mL of laccase, 14.39 psi steam explosion pressure and 24 h of incubation time. The experimental results obtained were in good agreement to predicted values, making it a reliable optimized model for five factors in combination to predict reducing sugar yield for ethanol production for bio-fuel industry.

Optimization of enzymatic saccharification of microwave pretreated sugarcane tops through response surface methodology for biofuel.

The optimization of biomass loading enzyme loading, surfactant concentration and incubation time, using response surface methodology (RSM) and Box Behnken design for enzymatic saccharification of sugarcane tops (SCT) for maximum recovery of fermentable sugars using crude cellulases, resulted in 90.24% saccharification efficiency. Maximum saccharification yield of 0.376 g/g glucose as substrate for ethanol production was observed at optimal conditions of 10% biomass loading (pretreated), 100FPU/g of cellulase loading, 0.04% (w/w) surfactant concentration and 72 h of incubation time.