Purpose/Objective(s) This prospective comparative study was carried out with the hypothesis that, in post operative oral cavity squamous cell carcinoma (PO-OCSCC) receiving adjuvant RT alone without concurrent chemotherapy, sparing DARS with dysphagia optimized IMRT (Do-IMRT) may lead to less acute and late dysphagia related toxicity than standard IMRT (S-IMRT). We had earlier reported acute toxicities. Herein, we report long term dysphagia related and clinical outcome of this study cohort. Materials/Methods Between February 2020 and June 2022, 56 PO-SCC patients without indications of concurrent chemotherapy (margin negative/no extra-nodal extension) were alternatively allocated into adjuvant Do-IMRT (n = 28) or S-IMRT (n = 28) arms. High risk and low risk planning target volumes received 60 Gray and 54 Gray respectively in 30 fractions over 6 weeks. Acute toxicities were assessed as per the CTCAE v5.0 and RTOG Late Morbidity Scoring Schema were used for late toxicities. Loco-regional control (LRC) was evaluated using Kaplan Meier method. Results Male: Female ratio for the entire cohort was 48:8. Rest of the patient characteristics is summarized in Table 1. 36.9 months was the median follow-up period (range = 15-48 months). When comparing Do-IMRT vs S-IMRT, Grade 1 and Grade 2 late dysphagia at 3 years were 12.3% vs. 26.8% (p = 0.07) and 0% vs. 22% (p = 0.023), respectively; Grade 1 and grade 2 xerostomia were 25.7% vs. 15.4% (p = 0.34) and 8.2% vs. 16.3% (p = 0.48) respectively. Grade 1 subcutaneous fibrosis was observed in 3 patients in the Do-IMRT arm and 4 patients in the S-IMRT arm. Dmean of ≥50 Gray to superior and middle pharyngeal constrictor muscle, supraglottic larynx; Dmean ≥40 Gray for inferior pharyngeal constrictor and ≥45 Gray for glottic larynx (GL) correlated with higher late grade ≥ 2 dysphagia (all p<0.05). 3-year LRC was 79.8% in Do-IMRT and 73.6% in S-IMRT (p = 0.32). Conclusion Sparing DARS with Do-IMRT leads to lesser late dysphagia in PO-OCSCC patients without compromising loco-regional control as compared to S-IMRT.
ABSTRACT Neuroblastomas are the most common extracranial solid tumor in the pediatric age group (~8%–10% of childhood neoplasms). Most cases of intracranial neuroblastomas occur due to metastasis from some primary extracranial sites and are known as secondary neuroblastomas. However, the occurrence of primary central nervous system neuroblastomas (PCN-NB) is very rare, and only a few cases and case series have been reported in the literature. PCN-NB is mainly an intra-axial pathology, and extra-axial involvement is mainly due to metastasis from some extracranial primary site with involvement of the skull bone. Herein we report a case of a 23-year-old female having a large extra-axial space-occupying lesion in the right frontal region that was mimicking a meningioma, and surprisingly the histopathology was suggestive of a supratentorial neuroblastoma. A right frontal craniotomy was made, and Simpson’s grade 1 excision of the tumor was done. The excised tissue was sent for histopathological examination. PCN-NB located extra-axially are extremely rare to occur. Due to inconsistent radiological imaging, it becomes very difficult to diagnose these tumors preoperatively, and these should be kept in mind as one of the differential diagnoses of extra-axial intracranial space-occupying lesions. Histopathological examination is crucial in diagnosing the intracranial neuroblastomas.
Purpose/Objective(s)We aim to evaluate the role of neoadjuvant chemotherapy followed by hypofractionated radiotherapy in locally advanced unresectable OCSCC in terms of acute toxicity and efficacy.Materials/Methods10 patients with locally advanced (T4a-T4b and N0 or N1-N2) inoperable OCSCC with good performance status were recruited in this single arm prospective study between December 2020-january 2022. All patients received 2 cycles of NACT (paclitaxel 175 mg /m2 on D-1, cisplatin 75 mg / m2 on D1 and D2 in divided doses) every three weekly followed by Hypofractionated Radiotherapy (RT), delivered by 3-dimensional conformal radiotherapy plan with a dose of 55Gray (Gy) in 22 fractions at 2.5Gy per fraction delivered 5 days a week in two phases. Acute toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and response was evaluated by WHO response criteria. The primary and secondary endpoints were clinical response rate and acute toxicity, respectively. Statistical analysis was done using statistical software.ResultsAll patients received 2 cycles of NACT. Median RT dose was 55Gy. overall treatment time (OTT) was 98 days (95-120). Median Duration of follow up was 10 months (8-13 months). Patients' characteristics are summarized in table 1. All the patients completed their treatment as per protocol. Weekly assessment of toxicity was done and recorded during radiotherapy. Patients having dysphagia (grade >2) was 40% (4) and patients having dysphagia (grade ≤ 2) was 60% (6). Patients having oral mucositis (grade >2) was 50% (5) and those having (grade ≤ 2) was 50% (5). Radiation dermatitis more than grade 2 was not observed in any patient. No patient developed grade-4 radiation toxicity. All patients were regularly followed up for response assessment both clinically and radiologically. At median follow up of 10 month, 20% (2) patients had complete response (CR), 70% (7) patients had partial response (PR) and 10% (1) had progressive disease (PD).ConclusionNeoadjuvant chemotherapy followed by hypofractionated radiotherapy in locally advanced unresectable OCSCC shows acceptable acute radiation toxicity and good efficacy. We aim to evaluate the role of neoadjuvant chemotherapy followed by hypofractionated radiotherapy in locally advanced unresectable OCSCC in terms of acute toxicity and efficacy. 10 patients with locally advanced (T4a-T4b and N0 or N1-N2) inoperable OCSCC with good performance status were recruited in this single arm prospective study between December 2020-january 2022. All patients received 2 cycles of NACT (paclitaxel 175 mg /m2 on D-1, cisplatin 75 mg / m2 on D1 and D2 in divided doses) every three weekly followed by Hypofractionated Radiotherapy (RT), delivered by 3-dimensional conformal radiotherapy plan with a dose of 55Gray (Gy) in 22 fractions at 2.5Gy per fraction delivered 5 days a week in two phases. Acute toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and response was evaluated by WHO response criteria. The primary and secondary endpoints were clinical response rate and acute toxicity, respectively. Statistical analysis was done using statistical software. All patients received 2 cycles of NACT. Median RT dose was 55Gy. overall treatment time (OTT) was 98 days (95-120). Median Duration of follow up was 10 months (8-13 months). Patients' characteristics are summarized in table 1. All the patients completed their treatment as per protocol. Weekly assessment of toxicity was done and recorded during radiotherapy. Patients having dysphagia (grade >2) was 40% (4) and patients having dysphagia (grade ≤ 2) was 60% (6). Patients having oral mucositis (grade >2) was 50% (5) and those having (grade ≤ 2) was 50% (5). Radiation dermatitis more than grade 2 was not observed in any patient. No patient developed grade-4 radiation toxicity. All patients were regularly followed up for response assessment both clinically and radiologically. At median follow up of 10 month, 20% (2) patients had complete response (CR), 70% (7) patients had partial response (PR) and 10% (1) had progressive disease (PD). Neoadjuvant chemotherapy followed by hypofractionated radiotherapy in locally advanced unresectable OCSCC shows acceptable acute radiation toxicity and good efficacy.
The existing wound care systems and sustained interest in the development of new generation dressings is a step towards a constant search for better and effective management of wound care. There were two major shifts in the development of wound care; the first one was to shift from dry to moist dressings whereby the healing process as well as time was augmented. The next major change came when the dressings were incorporated with antimicrobial compounds like silver, polyhexamethylene biguanide (PHMB), dialkyl carbamoyl chloride for providing healing and at the same time protection from the skin and soft tissue infections. Later on, use of adherent gauze and then vapour permeable films were developed. The recent developments in elastomeric polymer technology (hydrocolloids, polyurethane matrix, films etc.) along with this better understanding of the breathable adhesive technology provided us options for incorporating combined technology for new more efficient dressings. Even though there have been remarkable achievements in terms of wound care management, however, as yet there is no single dressing that can take care of all types of wounds.
Purpose/Objective(s) The standard treatment of locally advanced cervical carcinoma (LACC) is whole pelvic radiotherapy (WPRT) with concurrent cisplatin and intracavitary brachytherapy (ICBT). EBRT is typically delivered to a dose of 45-50.4 Gray at 1.8-2 Gray per fraction. While moderate hypofractionation (H-EBRT) have been practiced, prospective evidence is limited. We evaluated the role of H-EBRT in terms of toxicities and clinical outcome in LACC. Materials/Methods 50 patients of squamous cell carcinoma of cervix were recruited in this prospective interventional trial between December 2018-December 2021 (CTRI/2018/11/016415). Patients were treated with WPRT 40 Gray in 16 fractions over 3.5 weeks with boost to pelvic lymph nodes 10 Gray in 4 fractions with 3-DCRT and concurrent cisplatin weekly 40 mg/m2 followed by image guided high dose rate ICBT 7Gray in 4 fractions. Cumulative EQD2 (equivalent dose at 2 Gray per fraction) for high-risk clinical target volume and organs at risk were derived. Acute and late toxicities were recorded as per CTCAE version 4.0 and RTOG criteria respectively. Disease free survival (DFS) and overall survival (OS) were estimated by Kaplan Meier method Results Patient characteristics are summarized in Table 1. All patients completed intended course of treatment. 6 patients received nodal boost. Median number of concurrent chemotherapy cycles were 4 (range 3-5). Median (range) cumulative EQD2 for HR-CTV, rectum, bladder and sigmoid were 80.15 (68-104.9), 65.91 (51.1-75.18), 82.05 (58.58-94.96) and 55.96 (46.5-86.76) respectively. Acute ≥ Grade 2 and ≥ Grade 3 gastrointestinal (GI), genitourinary (GU), anemia, leucopenia, and thrombocytopenia were seen in 20 (40%) and 10 (20%), 5 (10%) and 3 (6%), 10 (20%) and 3 (6%), 15 (30%), and 4 (8%), 6 (12%), and 3 (6%), respectively. Late grade 2 and grade 3 GI toxicity was seen in 6 (12%) and 2 (4%) patients and late grade 2 GU toxicity were observed in 3 (6%) patients. Three patients had developed recurrence at the time of last follow-up and all three died from disease. Estimated 2- and 3-year overall survival was 94.9% and 90.6% respectively and 2- and 3-year DFS was 92.7% and 92.7% respectively. Conclusion Moderately hypo-fractionated WPRT is well tolerated with acceptable acute and late toxicity profiles and yielded excellent clinical outcome. This schedule would lead to lesser overall treatment time, increased compliance and also be resource sparing and cost effective. Longer follow up would yield more data on late toxicity. Randomized study comparing this schedule with conventional fractionated schedule is warranted.
Bioactive peptides are generated during milk fermentation or enzymatic hydrolysis. Lactobacillus (L) helveticus is commonly used to produce some types of fermented milk products. Fermented milk derived bioactive peptides are known to be beneficial in human health. Anti-hypertensive peptides play a dual role in the regulation of hypertension through the production of the vasoconstrictor angiotensin II and its inactivation of the vasodilator bradykinin. MALDI MS/MS, nano-LC/MS/MS and RP-HPLC were used to isolate peptides showing angiotensin converting enzyme inhibition (ACE-I) from 12% fermented skim milk using a combination of L. helveticus and Flavourzyme®. The fermentation procedure facilitated the identification of 133 anti-hypertensive peptides and 75% short chain amino acids, and the three with the highest ACE-I activity reduced blood pressure in a rat model of hypertension. The freeze- dried extract was supplemented in rodent chow. In this study 14-week-old male spontaneously hypertensive rats were fed for 10 weeks with the identified peptides added to chow and compared to controls supplemented with skim milk powder. Blood pressure (BP) decreased significantly (p < 0.05) from 6 to 10 weeks of FS groups (120/65 mmHg) compared with the NFS control groups, where the BP increased significantly (220/150 mmHg) (p < 0.05). The F6 fraction provided bioactive peptides with stronger antihypertensive properties than other fractions. Skim milk fermented by L. helveticus and Flavourzyme® generates several bioactive peptides which have a blood pressure lowering effect in hypertensive disease.
Adjuvant HYPO-RT with RT-TMZ is well tolerated in terms of acute toxicity and may be a good alternative to reduce overall treatment time and counteract tumor repopulation in PO- GBM. Further follow up of our study cohort will elucidate the clinical outcome of patients treated with this HYPO-RT approach.
L-asparaginase (EC 3.5.1.1) is used for the treatment of acute lymphocytic leukemia and food processing of starch rich foods for reducing the acrylamide formation. In our current efforts, we have immobilized the purified glutaminase-free recombinant Lasparaginase II of Pectobacterium carotovorum MTCC 1428 from Escherichia coli BL21 (DE3) on glutaraldehyde activated chitosan beads. The purified recombinant L-asparaginase II has no partial glutaminase activity which is a pre-requisite to reduce the possibility of side effects during the course of anticancer therapy. In order to study the best conditions for the performance of free enzymes and immobilized enzymes, response surface methodology was used to optimize the pH and temperature of the process conditions. It was found that the most favorable pH and temperature for the free enzyme were pH 7.83 and 47.64°C while for the immobilized enzyme, the optimum pH and temperature levels were found to be 7.88 and 48.07 °C. Furthermore, the thermal and pH studies of free and immobilized enzymes were studied under various combinations of pH and temperature and finally the thermodynamic parameters of free and immobilized glutaminase-free recombinant asparaginase were evaluated.
Inoperable patients of OC-SCC with good performance status treated with definitive CTRT with or without IC yielded complete response in approximately half of patients with acceptable toxicity profile. Loco-regional failure remains the predominant mode of failure. Future research including studies on biomarkers for better patient selection and treatment personalization is warranted.
Decalepis hamiltonii Wight & Arn. belongs to Asclepiadaceae family which is an ethno-pharmaceutically important monogenic plant species that is native to the Deccan peninsula forest areas of India. It is endangered due to habitat loss and over exploitation for volatile 2-hydroxy-4-methoxybenzaldehyde (HMB), which is an aromatic bioactive secondary metabolite. HMB is of great biological significance and is present in the plant’s tuberous roots. Plant cell culture is a viable alternative method for in vivo plant cultivation for secondary metabolites production. Callus induction with high biomass from the germinated root as explants for HMB production was optimised on Murashige and Skoog’s (MS) medium containing 3% (w/v) sucrose, supplemented with 1 μM 2,4-dichlorophenoxyacetic acid (2,4-D), 1 μM α- naphthaleneacetic acid (NAA) and 10 μM 6-benzylaminopurine (BAP) in dark incubation. Cell suspension cultures were established in 250 ml shake flasks, and each flask contained 50 ml of the same induction medium. Moreover, the pH 5.8, 3% sugar concentration and 120 rpm agitation speed in dark condition were suitable for high biomass production and the specific growth rate (µ) was 0.086 /day. Extraction of HMB was done by steam condensate methods from the biomass of cell suspension culture. Qualitative and quantification analyses of HMB were performed with gas chromatography (GC) and observed that 0.92 ± 0.02 mg/ml (0.092%) HMB were synthesized in the cell suspension culture.
CONTENTS 2.1 Postharvest Quality 19 2.1.1 Factors Affecting Quality 20 2.1.1.1 Preharvest Factors 20 2.1.1.2 Harvesting Factors 21 2.1.1.3 Postharvest Factors 24 2.2 Postharvest Physiological Processes 26 2.2.1 Ontogeny 26 2.2.2 Respiration 27 2.2.3 Transpiration and Water Stress 30 2.2.4 Ripening and Senescence 32 2.2.5 Phytohormone Effects 34 2.2.6 Physiological Disorders and Breakdowns 36 2.2.6.1 Disorders due to Mineral Deficiencies 38 2.2.6.2 Disorders due to Environmental Factors 38 2.2.7 Other Biochemical Changes 40 References 43
The quality of fruits and vegetables deteriorates progressively after harvest within a short time due to a series of physical, physiological, and pathological agents the produce is exposed to before reaching a consumer or a processor. Both quantitative and qualitative losses anywhere along the chain occur in the field, during packaging, storage, distribution, and transportation. Postharvest management practices facilitate the continuous supply of fruits and vegetables to fresh, minimally processed, and processed markets. A good quality processed product can only be possible when good quality raw materials are used in its manufacture. Postharvest treatments generally aim at preserving and/or enhancing the quality of fruits and vegetables by controlling the physiological, mechanical, and pathological agents responsible for both postharvest losses and degradation of quality. Heat treatment can also assist in controlling the postharvest disorders and enhancing the shelf life of fruits and vegetables by the formation of areas of amorphous wax and fewer surface cracks in apples after heat treatment.
SummaryThe effects of different pH treatments with and without heating on the characteristics of wheat gluten suspension was investigated. At pH 1, maximum changes in colour were observed with a concurrent 65% decrease in protein free‐thiol content compared to the control gluten. The SDS‐Extractability of protein (SDS‐EP) chromatogram eluted at lower retention time and the presence of bands at the top lane even during reducing conditions in SDS‐PAGE gel suggested complex formation involving bonds other than disulphides. An increase in the free‐amino group content and the presence of an additional peak at a higher retention time in the SDS‐EP chromatogram was suggestive of hydrolysis. At pH 2 and 3, similar decreases in SDS‐EPs and free‐thiol content indicated formation of complexes. When heated, the free‐thiol content of the dispersions increased compared to the non‐heated dispersions indicating disruption of disulphide bonds with changes in gluten structure and size distribution.
L-asparaginase (EC 3.5.1.1) is an important antineoplastic agent, used in the acute lymphoblastic leukemia chemotherapy and well known as food processing aid for reducing the acrylamide formation in starch rich foods. In the present study, we have cloned, expressed and purified recombinant L-asparaginase II of Erwinia carotovora subsp. atroseptica SCRI 1043 in E. coli. To study the best condition for performance of recombinant enzymes, pH and temperature of process conditions were optimized using response surface methodology. Optimal pH and temperature for enzyme were found to be 7.79 and 47.21 degrees C. Furthermore, the purified recombinant enzyme was subjected to thermal deactivation studies. pH and thermal stability of enzyme was studied at various combinations of pH and temperature. In addition, thermodynamic parameters of recombinant L-asparaginase II were evaluated. It was observed that recombinant L-asparaginase II enzyme is more stable at pH 8.5 at 35 degrees C relatively pH 6.5, 7.5 and 9.5. It was also observed that recombinant L-asparaginase II is more stable at pH 8.5 than pH 9.6 and 7.6 at higher temperature.
Effects of change in pH at drainage (6.2, 5.9, and 5.6), rennet concentration (0.1 and 0.3 mL rennet/L of milk) and casein to fat ratio (0.6, 0.7, and 0.8) on proteolytic characteristics of salt-reduced Cheddar cheese were investigated. Chemical composition, lactic acid bacteria and proteolysis were measured. At the same drainage pH, cheeses with C/F ratio 0.6 had significantly higher moisture and ash content compared other ratios. The pH decreased significantly from day 0 (right after pressing) to 120 day and then remained constant. Total LAB growth in cheeses made with 0.3 ml rennet /L was higher at the same C/F ratio and pH at drainage of 6.2. Total plate count at day 180 was significantly higher compared with day 0 (right after pressing). At the same drainage pH, C/F ratio and storage time, water soluble nitrogen contents in cheeses made with 0.3 ml/L rennet were higher compared with 0.1 ml/L. Total free amino acids and trichloroacetic acid-soluble nitrogen contents increased significantly during storage. More hydrophobic peaks appeared as the rennet concentration was increased from 0.1 to 0.3 ml/L. Extra-hydrophobic peptides % in cheese at day 0 and pH at drainage of 5.6, were higher compared to cheese where pH at drainage was 6.2. Increase in C/F ratio and rennet concentration, especially at low pH, showed similar proteolysis as cheese containing 2.5-3% salt.
The cross sections of 67 Zn, 92,96 Mo, 208 Pb(n,p) and 70 Zn, 100 Mo(n,2n) reactions have been evaluated using statistical nuclear model codes EMPIRE 3.2.2 and TALYS 1.8 at the neutron energy range from reactions threshold to 20 MeV. The variation in cross section with different optical model potential, level density models, and nuclear reaction models have been investigated at neutron energy 14.5 MeV. In this work, the pre-equilibrium emission contribution in the total cross section has also been verified in the neutron energy of 14.5 MeV. The calculated results were also compared with the experimental data being taken from EXFOR database.
Seven strains of selected probiotic bacteria were separately combined with Kluyveromyces marxianus LAF 4 to ferment 12% reconstituted skim milk (RSM) at 37 °C for 0–12 h. The growth characteristics of the probiotic strains and K. marxianus , pH levels, proteolytic activity and angiotensin‐converting enzyme inhibitory ( ACE ‐I) activity of the fermented RSM were measured. The highest ACE ‐I activity of 60% was for K. marxianus at 37 °C for 12 h ( P < 0.005) when compared to K. marxianus in combination with the probiotic bacterial strains.