Bioactive metabolites identification of the foxnut and broken millet-based nutritional bar using HR-MS.

The by-products of the grain processing industry are a vital resource for the valorization methods in the food industry. In comparison to the whole grain, the broken kernels and seeds own similar nutrient and bioactive compounds having multifaceted health properties. This study aims to develop a nutritional bar by utilizing the by-products from barnyard millet and foxnut with added sweeteners. Furthermore, high-resolution mass spectrometry (HR-MS) metabolomics was carried out in positive and negative both ion modes to identify the major bioactive compounds formed in the matrix of the best-optimized valorized bar. The formulation of the bar having 15 % foxnut flour and the barnyard flour each, was elucidated highest rheological and sensory scores. A sum of 29 bioactive metabolites has been observed in the obtained metabolome. Major metabolites were palmitoyl serinol, glycitein, persin, bufagargarizin, apigenin, carvone, etc. covering a wide area in the mass spectrum. The therapeutic value of these compounds is heart health promotion, anti-inflammatory, anti-carcinogenic, anti-diabetic, anti-microbial, etc. This work highlights the bioactivity of the valorized nutritional bar employing robust and accurate tool of mass spectrometry. The developed snack is a functional food for the consumers.

Comparative analysis of simultaneous integrated boost and sequential boost radiotherapy in node-positive cervical cancer: dosimetric and radiobiological considerations.

For locally advanced cervical cancer, the standard therapeutic approach involves concomitant chemoradiation therapy, supplemented by a brachytherapy boost. Moreover, an external beam radiotherapy (RT) boost should be considered for treating gross lymph node (LN) volumes. Two boost approaches exist with Volumetric Intensity Modulated Arc Therapy (VMAT): Sequential (SEQ) and Simultaneous Integrated Boost (SIB). This study undertakes a comprehensive dosimetric and radiobiological comparison between these two boost strategies. The study encompassed ten patients who underwent RT for cervical cancer with node-positive disease. Two sets of treatment plans were generated for each patient: SIB-VMAT and SEQ-VMAT. Dosimetric as well as radiobiological parameters including tumour control probability (TCP) and normal tissue complication probability (NTCP) were compared. Both techniques were analyzed for two different levels of LN involvement - only pelvic LNs and pelvic with para-aortic LNs. Statistical analysis was performed using SPSS software version 25.0. SIB-VMAT exhibited superior target coverage, yielding improved doses to the planning target volume (PTV) and gross tumour volume (GTV). Notably, SIB-VMAT plans displayed markedly superior dose conformity. While SEQ-VMAT displayed favorable organ sparing for femoral heads, SIB-VMAT appeared as the more efficient approach for mitigating bladder and bowel doses. TCP was significantly higher with SIB-VMAT, suggesting a higher likelihood of successful tumour control. Conversely, no statistically significant difference in NTCP was observed between the two techniques. This study's findings underscore the advantages of SIB-VMAT over SEQ-VMAT in terms of improved target coverage, dose conformity, and tumour control probability. In particular, SIB-VMAT demonstrated potential benefits for cases involving para-aortic nodes. It is concluded that SIB-VMAT should be the preferred approach in all cases of locally advanced cervical cancer.

The Utility of Galactomannan and Polymerase Chain Reaction Assays in Bronchoalveolar Lavage for Diagnosis of Chronic Pulmonary Aspergillosis.

The diagnosis of chronic pulmonary aspergillosis (CPA) is established by combined clinic-radio-microbiological criteria. Out of the different microbiological criteria, a positive serology for Aspergillus-specific IgG levels is the cornerstone of diagnosis. Alternatively, other microbiological evidence are sometimes sought viz., positive Aspergillus antigen (broncho-alveolar lavage fluid, i.e., BALF galactomannan ≥ 1.0), histopathological demonstration of the fungi following lung biopsy or resection, demonstration of hyaline septate hyphae in direct microscopy resembling Aspergillus spp. or its growth on a respiratory specimen. However, the exact roles of BALF- GM and the newer BALF-PCR have not been confirmed by studies till date. This study enrolled 210 patients with suspected CPA. Of the participants, 88 patients met the criteria for CPA, whereas 122 patients had an alternative diagnosis. The sensitivity-specificity of AsperGenius® PCR and "in-house" PCR were 52.27(36.69-67.54) %-33.78 (23.19-45.72) % and 36.36 (22.41-52.23) %-39.19 (28.04-51.23) % respectively. The sensitivity/specificity of BALF (> 1.0) and serum galactomannan (> 1.0) were 46.55% (33.34-60.13)/64.08% (54.03-73.3) and 29.82% (22.05-37.6)/86.84% (81.1-92.59) respectively. The optimal cut-off values for BALF-Galactomannan and serum galactomannan in diagnosing CPA were found to be 0.69 (sensitivity: 64%; specificity: 53%) and 0.458 (sensitivity: 67%; specificity: 64%) respectively. This results of this study suggests that Aspergillus PCR from BAL may not be a good "rule-in" test for diagnosing CPA. While the performances of GM in BAL and serum may be better than PCR, it should be best used in conjunction with other clinical, radiological, and other microbiological characteristics.

Evaluation of survival outcome and prognostic factors for oral cavity cancer treated with volumetric arc therapy.

PURPOSE: This study aimed to evaluate the survival outcomes and identify prognostic factors for patients with oral cavity cancer (OCC) who underwent adjuvant treatment with volumetric arc therapy (VMAT) using simultaneous integrated boost (SIB). METHODS: Data was collected for post-operated patients of carcinoma of oral cavity who received adjuvant VMAT with SIB between June 2018 and December 2022. The data was entered and analyzed using SPSS software version 20.0. Survival rates were estimated using Kaplan Meier method. To determine survival difference between the groups, log rank test was used. Multivariate analyses were performed with Cox proportional hazard model and p value < 0.05 was considered as significant. RESULTS: A total of 178 patients were included in the study. The median follow-up period was 26 months (range 3-56 months). The 3-year OS, DFS, and LRC rates were 78% (95% CI 77-79%), 76% (95% CI 74-77%), and 81% (95% CI 80-82%), respectively. Univariate analysis identified age ≥ 50 years, lymph node involvement, extracapsular extension (ECE), and N2-N3 disease as significant adverse prognostic factors for OS, DFS, and LRC. Multivariate analysis confirmed age ≥ 50 years and nodal involvement as independent predictors of worse OS, DFS, and LRC. Additionally, ECE independently affected OS and DFS. CONCLUSION: Adjuvant treatment with VMAT using SIBin patients with OCC is effective. Age and nodal involvement had significant impact on LRC, DFSand OS while ECE on DFSand OS.

Survival outcome and prognostic factors post inadvertent hysterectomy in carcinoma cervix treated with salvage chemo-radiation.

INTRODUCTION: The standard of care for treating early invasive cervical cancer is radical hysterectomy or radiation alone while chemo-radiation is a definitive treatment for advanced disease. Occasionally, a simple hysterectomy is performed in the cancer cervix and these patients merit adjuvant treatment in view of the high chances of loco-regional recurrences. The aim of the study was to analyze the survival outcome of these patients treated with salvage chemo-radiotherapy and also to determine the prognostic factors affecting survival. MATERIALS AND METHODS: The medical records of all patients with cervical cancer post simple hysterectomy outside and who received salvage treatment in our department between 2014 and 2020 were retrieved. The data regarding clinical, treatment details and survival were analyzed. RESULTS: A total of 198 patients were included. Median follow-up duration was 45.5 months. Gross disease and lymphadenopathy were seen in 60% and 28% patients, respectively. The 5-year progression-free survival(PFS) and overall survival(OS) was 75% and 76%, respectively. Concurrent chemotherapy alone or in combination with induction chemotherapy using three-drug regimens showed better survival compared to those treated by radiation alone. On multivariate analysis, factors found to be adversely affecting OS and PFS were lymph node (LN) size of more than 2 cm, non-squamous histology, overall treatment time(OTT) of more than 12 weeks and use of non three-drug chemotherapy regimen. CONCLUSION: Subtotal hysterectomy results in a higher incidence of local recurrence of disease. Factors that impair the outcome in this sub-group of patients are gross lymphadenopathy, non-squamous histology and prolong OTT.

Clinico-epidemiological profile and treatment outcome in adolescents and young patients of rectal cancer attending a tertiary cancer center.

INTRODUCTION: The incidence of colorectal cancer in young adults is on an increasing trend. It is observed that this subgroup of patients has an aggressive disease and carries a poorer prognosis compared to its older counterpart. This study aimed to analyze the incidence, treatment outcome, and prognostic factors in adolescents and young adults with rectal cancer attending a tertiary cancer center in North India. MATERIALS AND METHODS: We retrospectively analyzed 50 patients of histologically proven rectal cancer, aged up to 30 years, treated at our center between 2015 and 2019. The clinical, demographic, and pathological parameters were studied in all these patients. Kaplan-Meier survival analysis was used to find out survival. Univariate analysis was performed to assess prognostic factors. RESULTS: The incidence was 26.4% at our center with a median age of 28 years. Bleeding per rectum was the commonest complaint. Most of them had signet ring cell histology (26%). The median overall survival was 16 months. Survival was significantly better in patients having bleeding per rectum as an initial complaint (P = 0.009), absence of lymphovascular invasion (LVI) (P = 0.005), and perineural invasion (PNI) (P = 0.002), who received complete planned treatment compared to patients who could not receive either of the modality (P < 0.001). Patients who did not receive radiotherapy (RT) had the worst outcomes compared to those who received RT in any form. RT dose of 50.4 Gy was found to be superior as compared to other schedules. There was no significant difference in survival with gender, tumor stage, grade, type of surgery, or chemotherapy regimen. CONCLUSION: The majority of patients presented in an advanced stage. Therefore, bleeding per rectum should be properly and timely investigated in all these young patients. Early detection and complete treatment are paramount to improving the outcome.

Evaluation of survival outcomes and prognostic factors of carcinoma anal canal at a tertiary cancer center.

CONTEXT: Concurrent chemoradiotherapy is considered a standard of care for patients with carcinoma anal canal. Being an unusual malignancy, there is limited Indian data regarding survival outcomes and prognostic factors. AIM: To evaluate survival outcomes and associated prognostic factors in patients with carcinoma anal canal treated with radical intent. METHODS AND MATERIAL: Patients with squamous cell carcinoma of the anal canal, treated with radical intent between 2015 and 2019 were included in the study. Data regarding the baseline characteristics of the patients and treatment outcomes were collected and analyzed. Survival rates were estimated using Kaplan-Meier method. To determine survival difference between the groups, log-rank test was used. Multivariate analyses were performed with Cox proportional hazard models and P value < 0.05 was considered significant. RESULTS: Forty-two patients were identified after applying suitable eligibility criteria. The median age was 55 years (range: 26-80 years).The median follow-up duration was 23.5 months (range: 1.9-51.9 months). The 3-year overall survival (OS), disease-free survival (DFS), and locoregional (LRC) were 78.5%, 53.1%, and 66.4%, respectively. On multivariate analysis, inferior DFS was significantly affected by lack of concurrent chemotherapy (CT) (hazard ratio [HR], 11.50; 95% confidence interval [CI], 1.92-68.78; P = 0.007) and radiotherapy (RT) dose of 45 Gy or less (HR, 35.96; 95% CI, 6.32-204.56; P = 0.000). CONCLUSION: For patients of carcinoma anal canal, concurrent CT and RT dose are independent prognostic factors influencing DFS.

Hiccups: An atypical side effect experienced during chemo-radiotherapy in carcinoma nasopharynx.

ABSTRACT: Nasopharyngeal carcinoma is an uncommon cancer but has a distinct racial and geographic distribution. Patient presents with constellation of signs and symptoms due to its vicinity to critical structures and are best treated by conformal concurrent chemo-radiotherapy. We present a case of 45-year-old male diagnosed with carcinoma nasopharynx, referred to us for radiotherapy after three cycles of neoadjuvant chemotherapy. As per the prevailing standard of care, patient was planned for radiotherapy by volumetric arc technique with concurrent cisplatin. Initial days of treatment were uneventful. After fourth week of treatment, patient developed persistent hiccup which was not relieved on conservative medications. Plan was re-evaluated and it revealed maximum dose of 54.6 Gy to the brainstem. Radiotherapy induced edema that could have stimulated vagus nerve leading to hiccups was suspected. Patient was started on injectable steroid and chlorpromazine. There was prompt recovery from the symptom within five days of conservative treatment.

Diagnostic Accuracy of Plasma Cystatin C and Renal Resistive Index for Acute Kidney Injury in Critically Ill Patients: A Prospective Observational Study.

Background: Acute kidney injury (AKI) is a quite common problem in critically ill patients. Serum cystatin C has emerged as a marker of AKI. This study was aimed to evaluate the diagnostic ability of serum Cystatin-C and Renal Resistive Index in prediction of AKI among critically ill patients. Methodology: This prospective observational study was carried out in the department of Medicine, over a period of one year. After informed consent and ethical clearance total 120 critically ill patients suffering from sepsis were enrolled, out of which 70 patients developed AKI while 50 did not develop AKI during treatment in Intensive care unit (ICU). Serum cystatin C was measured on day 1 by particle-enhanced immune nephelometric assay, Renal resistive index (RRI) calculated by ratio of the velocities of arterial perfusion throughout the cardiac phase and glomerular filtration rate was measured on days 1, 3, and 7 respectively. Results: S. cystatin C value was significantly higher(>3times) in AKI patients (14.07±4.8 mcg/ml) as compared to those who did not develop AKI (4.28±3.27 mcg/ml) (p<0.001). After ROC analysis it was found that day1, S. cystatin C, at cut off value of ≥9.29 mcg/ml had diagnostic accuracy 90% with sensitivity 91%, specificity89% and PPV 95.5%. While RRI value on day 7, at cut-off value of ≥0.72, had diagnostic accuracy 98%, sensitivity (98.6%) and specificity (96.7%) for AKI with 98.6% PPV, 96.7% NPV. Conclusion: Serum cystatin C appears to be a promising bio- markers for early diagnosis of AKI in critically ill patients. Whereas, RRI although non-invasive had good diagnostic accuracy but it diagnosed AKI after few days thus diagnosis of kidney injury delayed.

Electrification at water-hydrophobe interfaces.

The mechanisms leading to the electrification of water when it comes in contact with hydrophobic surfaces remains a research frontier in chemical science. A clear understanding of these mechanisms could, for instance, aid the rational design of triboelectric generators and micro- and nano-fluidic devices. Here, we investigate the origins of the excess positive charges incurred on water droplets that are dispensed from capillaries made of polypropylene, perfluorodecyltrichlorosilane-coated glass, and polytetrafluoroethylene. Results demonstrate that the magnitude and sign of electrical charges vary depending on: the hydrophobicity/hydrophilicity of the capillary; the presence/absence of a water reservoir inside the capillary; the chemical and physical properties of aqueous solutions such as pH, ionic strength, dielectric constant and dissolved CO2 content; and environmental conditions such as relative humidity. Based on these results, we deduce that common hydrophobic materials possess surface-bound negative charge. Thus, when these surfaces are submerged in water, hydrated cations form an electrical double layer. Furthermore, we demonstrate that the primary role of hydrophobicity is to facilitate water-substrate separation without leaving a significant amount of liquid behind. These results advance the fundamental understanding of water-hydrophobe interfaces and should translate into superior materials and technologies for energy transduction, electrowetting, and separation processes, among others.

Mitigating cavitation erosion using biomimetic gas-entrapping microtextured surfaces (GEMS).

Cavitation refers to the formation and collapse of vapor bubbles near solid boundaries in high-speed flows, such as ship propellers and pumps. During this process, cavitation bubbles focus fluid energy on the solid surface by forming high-speed jets, leading to damage and downtime of machinery. In response, numerous surface treatments to counteract this effect have been explored, including perfluorinated coatings and surface hardening, but they all succumb to cavitation erosion eventually. Here, we report on biomimetic gas-entrapping microtextured surfaces (GEMS) that robustly entrap air when immersed in water regardless of the wetting nature of the substrate. Crucially, the entrapment of air inside the cavities repels cavitation bubbles away from the surface, thereby preventing cavitation damage. We provide mechanistic insights by treating the system as a potential flow problem of a multi-bubble system. Our findings present a possible avenue for mitigating cavitation erosion through the application of inexpensive and environmentally friendly materials.

Proof-of-Concept for Gas-Entrapping Membranes Derived from Water-Loving SiO2/Si/SiO2 Wafers for Green Desalination.

Desalination through direct contact membrane distillation (DCMD) exploits water-repellent membranes to robustly separate counterflowing streams of hot and salty seawater from cold and pure water, thus allowing only pure water vapor to pass through. To achieve this feat, commercial DCMD membranes are derived from or coated with water-repellent perfluorocarbons such as polytetrafluoroethylene (PTFE) and polyvinylidene difluoride (PVDF). However, the use of perfluorocarbons is limiting due to their high cost, non-biodegradability, and vulnerability to harsh operational conditions. Unveiled here is a new class of membranes referred to as gas-entrapping membranes (GEMs) that can robustly entrap air upon immersion in water. GEMs achieve this function by their microstructure rather than their chemical make-up. This work demonstrates a proof-of-concept for GEMs using intrinsically wetting SiO2/Si/SiO2 wafers as the model system; the contact angle of water on SiO2 is θo ≈ 40°. Silica-GEMs had 300 µm-long cylindrical pores whose diameters at the (2 µm-long) inlet and outlet regions were significantly smaller; this geometrically discontinuous structure, with 90° turns at the inlets and outlets, is known as the "reentrant microtexture". The microfabrication protocol for silica-GEMs entails designing, photolithography, chrome sputtering, and isotropic and anisotropic etching. Despite the water loving nature of silica, water does not intrude silica-GEMs on submersion. In fact, they robustly entrap air underwater and keep it intact even after six weeks (>106 seconds). On the other hand, silica membranes with simple cylindrical pores spontaneously imbibe water (< 1 s). These findings highlight the potential of the GEMs architecture for separation processes. While the choice of SiO2/Si/SiO2 wafers for GEMs is limited to demonstrating the proof-of-concept, it is expected that the protocols and concepts presented here will advance the rational design of scalable GEMs using inexpensive common materials for desalination and beyond.

Rendering SiO2/Si Surfaces Omniphobic by Carving Gas-Entrapping Microtextures Comprising Reentrant and Doubly Reentrant Cavities or Pillars.

We present microfabrication protocols for rendering intrinsically wetting materials repellent to liquids (omniphobic) by creating gas-entrapping microtextures (GEMs) on them comprising cavities and pillars with reentrant and doubly reentrant features. Specifically, we use SiO2/Si as the model system and share protocols for two-dimensional (2D) designing, photolithography, isotropic/anisotropic etching techniques, thermal oxide growth, piranha cleaning, and storage towards achieving those microtextures. Even though the conventional wisdom indicates that roughening intrinsically wetting surfaces (θo < 90°) renders them even more wetting (θr < θo < 90°), GEMs demonstrate liquid repellence despite the intrinsic wettability of the substrate. For instance, despite the intrinsic wettability of silica θo ≈ 40° for the water/air system, and θo ≈ 20° for the hexadecane/air system, GEMs comprising cavities entrap air robustly on immersion in those liquids, and the apparent contact angles for the droplets are θr > 90°. The reentrant and doubly reentrant features in the GEMs stabilize the intruding liquid meniscus thereby trapping the liquid-solid-vapor system in metastable air-filled states (Cassie states) and delaying wetting transitions to the thermodynamically-stable fully-filled state (Wenzel state) by, for instance, hours to months. Similarly, SiO2/Si surfaces with arrays of reentrant and doubly reentrant micropillars demonstrate extremely high contact angles (θr ≈ 150°-160°) and low contact angle hysteresis for the probe liquids, thus characterized as superomniphobic. However, on immersion in the same liquids, those surfaces dramatically lose their superomniphobicity and get fully-filled within <1 s. To address this challenge, we present protocols for hybrid designs that comprise arrays of doubly reentrant pillars surrounded by walls with doubly reentrant profiles. Indeed, hybrid microtextures entrap air on immersion in the probe liquids. To summarize, the protocols described here should enable the investigation of GEMs in the context of achieving omniphobicity without chemical coatings, such as perfluorocarbons, which might unlock the scope of inexpensive common materials for applications as omniphobic materials. Silica microtextures could also serve as templates for soft materials.

MoS2-Modified Curcumin Nanostructures: The Novel Theranostic Hybrid Having Potent Antibacterial and Antibiofilm Activities against Multidrug-Resistant Hypervirulent Klebsiella pneumoniae.

The recent emergence of hypervirulent clinical variants of Klebsiella pneumoniae (hvKP) causing community-acquired, invasive, metastatic, life-threatening infections of lungs, pleura, prostate, bones, joints, kidneys, spleen, muscles, soft-tissues, skin, eyes, central nervous system (CNS) including extrahepatic abscesses, and primary bacteremia even in healthy individuals has posed stern challenges before the existing treatment modalities. There is therefore an urgent need to look for specific and effective therapeutic alternatives against the said bacterial infection or recurrence. A new type of MoS2-modified curcumin nanostructure has been developed and evaluated as a potential alternative for the treatment of multidrug-resistant isolates. The curcumin quantum particles have been fabricated with MoS2 via a seed-mediated hydrothermal method, and the resulting MoS2-modified curcumin nanostructures (MQCs) have been subsequently tested for their antibacterial and antibiofilm properties against hypervirulent multidrug-resistant Klebsiella pneumoniae isolates. In the present study, we found MQCs inhibiting the bacterial growth at a minimal concentration of 0.0156 µg/mL, while complete inhibition of bacterial growth was evinced at concentration 0.125 µg/mL. Besides, we also investigated their biocompatibility both in vitro and in vivo. MQCs were found to be nontoxic to the SiHa cells at a dose as high as 1024 µg/mL on the basis of the tested adhesion, spreading of the cells, and also on the various serological, biochemical, and histological investigations of the vital organs and blood of the Charles Foster Rat. These results suggest that MQCs have potent antimicrobial activities against hvKP and other drug resistant isolates and therefore may be used as broad spectrum antibacterial and antibiofilm agents.

Deletion of Dictyostelium discoideum Sir2A impairs cell proliferation and inhibits autophagy.

Sirtuins are a family of deacetylases (Class III histone deacetylases) with evolutionarily conserved functions in cellular metabolism and chromatin regulation. Out of the seven human Sirtuins, the function of Sirt2 is the least understood. The purpose of the present study was to investigate the role of Sir2A, a homolog of human Sirt2 in Dictyostelium discoideum (Dd), a lower eukaryote. We created both overexpressing and deletion strains of Ddsir2A to analyse its functions. We observed sir2A mRNA expression throughout development and the transcript was present in the prespore/spore region of multicellular structures developed. They show a preference towards prestalk/stalk pathway when co-developed with wildtype cells during chimera formation. Deletion strain showed a multi-tipped phenotype, decrease in cell proliferation and inhibition of autophagy. In conclusion, our results show low cAMP levels, reduced cell-adhesion, weak cell migration and impaired autophagy to be responsible for the phenotype shown by the null cells. This study provides new insights into the functions of Ddsir2A.

A Randomized Prospective Study of Concurrent Chemo-Radiotherapy vs Accelerated Hyperfractionation in Advanced Cancer of Head and Neck.

INTRODUCTION: Locally advanced unresectable squamous cell carcinoma of head and neck has poor locoregional control when treated with conventionally fractionated Radiation Therapy (RT) alone. However, Concurrent Chemo-Radiotherapy (CRT) and altered fractionated RT schedules like Accelerated Hyperfractionation (AHF) are two different treatment strategies that have shown to be associated with better efficacy as compared to conventional RT alone in such cases. AIM: Aim of the study was to compare these two treatment strategies i.e., CRT and AHF radiation treatment to know which is better in terms of clinical outcome and toxicity in patients of locally advanced unresectable squamous cell carcinoma of head and neck. MATERIALS AND METHODS: A prospective randomized trial was done to compare the effect of CRT and of AHF radiation treatment in locally advanced unresectable head and neck cancer on 15 patients in each arm and followed up over three months period. RESULTS: At the end of three months after completion of treatment protocol, complete response was 62% in CRT arm and 53% in AHF arm. In CRT arm and AHF arm, Grade 3 skin reactions were observed in 100% and 87%, grade 3 mucosal reactions were in 62% and 67% of cases, respectively. Three patients died in CRT arm (two due to myelosuppression and associated infection; one during the treatment and another after two weeks of treatment completion. The third patient expired after one month of treatment completion at his native place due to unknown reason). One patient died in AHF arm (during treatment due to cardiac event). CONCLUSION: Efficacy of AHF was comparable to CRT with lesser toxicity. So the present study suggests that AHF should be preferred over CRT in locally advanced, unresectable, squamous cell head and neck cancer followed over three months non-treatment period.

Retrospective Analysis of Efficacy and Toxicity of Hypo-fractionated Radiotherapy in Breast Carcinoma.

INTRODUCTION: The conventional dose fractionation of adjuvant radiotherapy (RT) to whole breast is 45-50 Gy in 25 fractions as 1.8-2.0-Gy per fraction. Lumpectomy cavity with a 1.5-2-cm margin receieves additional 10- 16 Gy doseas boost. Alternative dose fraction schedules used in various randomised trials have established the role of hypofractionated radiotherapy (HRT) in early breast cancer. HRT allows time and cost saving thus better patient compliance. However the efficacy and toxicity of HRT in locally advanced breast cancer is still under evaluation. AIM: To study the toxicity and efficacy of Hypofractionated Radiotherapy (HRT) as compared to Conventional Radiotherapy (CRT) in breast cancer at our centre. MATERIALS AND METHODS: A retrospective analysis of breast cancer patients treated between October 2012- September 2014 with adjuvant radiation therapy as CRT or HRT. The data of these patients was retrieved and analysed regarding demographic profile, stage at presentation, pathological type, extent of surgery, chemotherapy, efficacy and toxicity of HRT. The toxicity assessment was done as per RTOG toxicity criteria. The data were analysed using SPSS software version 20.0. RESULTS: A total of 100 patients with carcinoma breast who received radiotherapy over two years were analysed. Age ranged from 18-90 years, mean 49.15 ± 12.7 years. Fifty-five patients were post-menopausal, predominant clinical feature was painless lump in the breast (98%). Early stage (Stage I and II) constituted 41%, locally advanced disease in 59%. Modified radical mastectomy was done in 75%, breast conserving surgery in 25%. A 56 patients received HRT and 44 were treated with CRT. The most common acute toxicity was skin grade I. An 18% patients in HRT arm and 30% patients in conventional arm developed grade II skin toxicity (p=0.23). Dysphagia grade I was seen in 10% cases in CRT arm and 12% in HRT arm. The median follow-up period was 11.3 months with 2 loco-regional failures in each arm. CONCLUSION: HRT seems to be equally efficacious and no more toxic than CRT in carcinoma breast even in unselected sub-group of patients.

Carcinoma of the oesophagus, with multiple cutaneous metastases.

A 42-year-old woman was referred, for adjuvant treatment, by an oncosurgeon (outside our centre) after a transhiatal oesophagectomy and gastric pull-up for middle one-third squamous cell carcinoma of the oesophagus pT3N1M0. She underwent adjuvant chemoradiotherapy (CRT) to the tumour bed, regional nodes and scar. RT dose planned was 45 Gy in 25 fractions over 5 weeks. During the second week of RT, a painful nodule was observed over the lower back and cytology was positive for squamous cell carcinoma. Hypofractionated radiotherapy (RT) was planned for this skin nodule as 30 Gy in 10 fractions over 2 weeks using electron beams for pain palliation. Two months later, another nodule developed at the surgical scar on the anterior abdominal wall along with lung and liver metastases. This nodule was also given palliative RT. The patient tolerated the treatment well and had partial pain relief, and, in view of poor prognosis, was advised best supportive care.

Gene dosage-dependent rescue of HSP neurite defects in SPG4 patients' neurons.

The hereditary spastic paraplegias (HSPs) are a heterogeneous group of motorneuron diseases characterized by progressive spasticity and paresis of the lower limbs. Mutations in Spastic Gait 4 (SPG4), encoding spastin, are the most frequent cause of HSP. To understand how mutations in SPG4 affect human neurons, we generated human induced pluripotent stem cells (hiPSCs) from fibroblasts of two patients carrying a c.1684C>T nonsense mutation and from two controls. These SPG4 and control hiPSCs were able to differentiate into neurons and glia at comparable efficiency. All known spastin isoforms were reduced in SPG4 neuronal cells. The complexity of SPG4 neurites was decreased, which was paralleled by an imbalance of axonal transport with less retrograde movement. Prominent neurite swellings with disrupted microtubules were present in SPG4 neurons at an ultrastructural level. While some of these swellings contain acetylated and detyrosinated tubulin, these tubulin modifications were unchanged in total cell lysates of SPG4 neurons. Upregulation of another microtubule-severing protein, p60 katanin, may partially compensate for microtubuli dynamics in SPG4 neurons. Overexpression of the M1 or M87 spastin isoforms restored neurite length, branching, numbers of primary neurites and reduced swellings in SPG4 neuronal cells. We conclude that neurite complexity and maintenance in HSP patient-derived neurons are critically sensitive to spastin gene dosage. Our data show that elevation of single spastin isoform levels is sufficient to restore neurite complexity and reduce neurite swellings in patient cells. Furthermore, our human model offers an ideal platform for pharmacological screenings with the goal to restore physiological spastin levels in SPG4 patients.