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As a consequence of recent habitat fragmentation, the free movement of Asian Elephants all over India has been interfered up to a great extent. This largest terrestrial mammal very existence is now under threat due to various reasons such as persecution for its ivory and blockage of migratory routes due to construction of human developmental activities. Shrinking elephants’ habitats due to linear developments such as railroads, motorways and canals and human habitation in and around the protected areas give rise to foraging and migratory problems, resulting ultimately in man-elephants conflicts, confrontation between herds and accidental deaths. This poster discusses in detail, threats faced by Wild Asian Elephants in the sub Himalayan region in Rajaji National Park, Uttranchal, India. Various case studies of difficulties faced by elephants because of railroad, motorway & irrigation and hydroelectric canals in the region are also discussed. River Ganges flows through the habitat for about 20-km & divides it in two parts. The man-made barriers have shrunk the width of habitat along the river Ganges from 20- km to roughly 4- km. The railroad and motorway on the right and the irrigation & hydroelectric canal on the left of the Ganges have restricted the access of the elephants to the legendary river Ganges, the irresistible attraction for the Wild Asian Elephants, which they have to visit daily for drinking, bathing and beating the heat in summer months. Therefore, the elephants look for alternate sources of water and food and as a result they enter human habitation and croplands, leading to the man-elephant conflicts. Moreover, with rail tracks in the vicinity, there have been numerous elephant’ deaths due to speeding trains. The frequent confrontations of elephants with moving traffic on railroad and highway have made them irritable, restless & prone to accidents. This poster examines the disastrous effects of improper design and construction of crossings on the age-old migration tracks and the existing linear developments and how they could be rectified in an animal-friendly way. The poster also suggests practical solutions to reduce the threats to elephants and to their habitats, ensuring sustainability of viable elephant population in a habitat shrunk by human activity.

Objective: The objective of this study was to validate the 'Functional Assessment of Chronic Illness Therapy-Spiritual-Well-being-Expanded(FACIT-SpEx) Version 4' tool in Malayalam and assess its feasibility among advanced cancer patients receiving palliative care., Materials and Methods: The study was carried out at the outpatient Department of Cancer Palliative Medicine of Malabar Cancer Centre between November 2022 and June 2023. Initially, the FACIT-Sp-Ex version 4 tool with 23 items was translated into the Malayalam language with a forward-backward translation procedure. This was followed by pilot testing in 10 advanced adult cancer patients receiving palliative care who could read and comprehend the Malayalam language. After answering the draft version of the validated tool, patients responded to questions from a Malayalam-translated cognitive debriefing script., Results: The process of translation and cross-cultural adaptation went on smoothly with very few hurdles. The Malayalam terms used in three items Sp 7 , Sp 9 and Sp 23 when back translated were found to be different from the source. These issues were resolved with the use of the most suitable translations and closest equivalents available in Malayalam. In the pilot testing, the majority (70%) of the patients were female. The mean age of patients was 45.90 (standard deviation [SD] = 7.62) years. Carcinoma breast (50%) was the most common type of cancer. All the patients knew their diagnosis, while only 80% knew the prognosis. Almost 90% of the patients were receiving some form of palliative anticancer treatment. All patients completed the draft version of the validated tool. The mean spiritual well-being score measured using this validated tool was 71.20 (SD = 15.10). Analysis of the debriefing interviews revealed that the Malayalam version was easy to complete, relevant, and appropriate., Conclusion: Linguistic validation and cognitive debriefing produced the Malayalam translated FACIT-Sp-Ex version 4 tool conceptually equivalent to the original FACIT-Sp-Ex version 4 tool, and it is feasible for its use., Competing Interests: There are no conflicts of interest., (© 2024 Published by Scientific Scholar on behalf of Indian Journal of Palliative Care.)

Introduction: Dental extraction is a common oral surgery procedure, but it can lead to unpredictable changes in alveolar bone structure, which can complicate future rehabilitation with prostheses. Socket preservation aims to reduce bone and soft tissue loss after extraction and involves various techniques using different materials. Autogenous bone is considered the gold standard for grafts, while autologous platelet concentrates like platelet-rich fibrin (PRF) have been used for tissue healing. This study aims to radiographically assess the bone remodeling of freshly extracted socket filled with Activated Platelet Rich Fibrin (APRF) and PRF., Materials and Methods: A randomized controlled study was conducted on 60 patients undergoing tooth extraction as atraumatic as possible. Patients were divided into two groups: one receiving APRF with 10% Calcium Chloride as activating agent and the other PRF. Radiographic assessments were done using Kelley et al. scoring criteria at various time intervals, and statistical analyses were performed to evaluate the results., Results: In this study we found increased bone density in extracted socket filled with APRF at any given time interval compared to PRF which is statistically significant. The maxilla demonstrated better bone formation compared to the mandible. Gender, age, and site also influenced bone formation, with females showing differences in lamina dura and overall density., Discussion: PRF is rich in growth factors, promoting osteoblast formation and angiogenesis. Activation with calcium chloride accelerates clot formation and the release of growth factors. This study's radiographic data suggests that APRF may be more effective than PRF in promoting socket preservation and bone formation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Standardizing image datasets is essential for facilitating overall visual comparisons and enhancing compatibility with image-processing workflows. One way to achieve homogeneity for images containing a single object is to align the object to a common orientation. Here, we propose the Virtual Orientation Tools (VOTj): a set of Fiji plugins to center and align an object of interest in images to a vertical or horizontal orientation. To process an image, the plugin requires either a mask outlining the object or a rough annotation of the object directly drawn by the user in the image. The current object orientation is retrieved using Principal Component Analysis (PCA), from which the optimal alignment is derived. The plugins support multi-dimensional images to allow, e.g., aligning individual time points of a time-lapse. The tools can be used for a variety of samples and imaging modalities. Besides, the plugins enable the interactive alignment of a list of images from a directory for batch execution and can be included in custom image-processing workflows using macro-recording., Competing Interests: The authors declare that there are no conflicts of interest present., (Copyright: © 2024 by the authors.)

Pelvic exenteration is potentially curative for operable locally advanced primary and locally recurrent rectal cancers. R0 resection is associated with higher survival. This procedure is associated with low mortality rates but high postoperative morbidity proportional to the extent of resection. This study was done to find out the survival outcome and morbidity associated with this procedure and to determine prognostic factors associated with postoperative outcomes. Seventy-three patients with rectal cancer underwent pelvic exenteration between January 2009 and December 2020. Sixty-six patients had locally advanced rectal cancer and 7 patients had recurrent cancer. All patients with primary tumors were evaluated with MRI pelvis and CT scan of the chest and abdomen while patients with recurrence were evaluated with a PET scan. The median follow-up duration was 39 months. The majority of patients were in the age group 40-69 years. Thirty patients were males and 43 were females. The 30-day postoperative major morbidity was reported in 28 patients (38.4%). The most common morbidity was wound dehiscence. The mean overall survival (OS) was 110.6 months (95% CI, 97.5-123.7) and mean disease free survival (DFS) was 85 months (95% CI, 71.0-100.4). R0 resection was associated with favorable overall survival. Tailored exenterations were associated with low morbidity. En bloc partial sacrectomy helped achieve R0 resection in patients who underwent the procedure. Extended resections yielded high R0 resection rates with favorable survival (65 months) but were associated with high morbidity. These procedures shall be best practiced in high-volume institutes of expertise., Supplementary Information: The online version contains supplementary material available at 10.1007/s13193-024-01918-w., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Indian Association of Surgical Oncology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Objective: The 2x2 factorial design is an effective method that allows for multiple comparisons, especially in the context of interactions between different interventions, without substantially increasing the required sample size. In view of the considerable preclinical evidence for Curcumin and Metformin in preventing the development and progression of head and neck squamous cell carcinoma (HNSCC), this study describes the protocol of the clinical trial towards applying the drug combination in prevention of second primary tumors., Methods: We have applied the trial design to a large phase IIB/III double-blind, multi-centric, placebo-controlled, randomized clinical trial to determine the safety and efficacy of Metformin and Curcumin in the prevention of second primary tumours (SPT) of the aerodigestive tract following treatment of HNSCC (n=1,500) [Clinical Registry of India, CTRI/2018/03/012274]. Patients recruited in this trial will receive Metformin (with placebo), Curcumin (with placebo), Metformin, and Curcumin or placebo alone for a period of 36 months. The primary endpoint of this trial is the development of SPT, while the secondary endpoints are toxicities associated with the agents, incidence of recurrence, and identifying potential biomarkers. In this article, we discuss the 2x2 factorial design and how it applies to the head and neck cancer chemoprevention trial., Conclusion: 2x2 factorial design is an effective trial design for chemoprevention clinical trials where the effectiveness of multiple interventions needs to be tested parallelly.

Starvation and refeeding are mostly unanticipated in the wild in terms of duration, frequency, and nutritional value of the refed state. Notwithstanding this, organisms mount efficient and reproducible responses to restore metabolic homeostasis. Hence, it is intuitive to invoke expectant molecular mechanisms that build anticipatory responses to enable physiological toggling during fed-fast cycles. In this regard, we report anticipatory biogenesis of oscillatory hepatic microRNAs that peak during a fed state and inhibit starvation-responsive genes. Our results clearly demonstrate that the levels of primary and precursor microRNA transcripts increase during a fasting state, in anticipation of a fed response. We delineate the importance of both metabolic and circadian cues in orchestrating hepatic fed microRNA homeostasis in a physiological setting. Besides illustrating metabo-endocrine control, our findings provide a mechanistic basis for the overarching influence of starvation on anticipatory biogenesis. Importantly, by using pharmacological agents that are widely used in clinics, we point out the high potential of interventions to restore homeostasis of hepatic microRNAs, whose deregulated expression is otherwise well established to cause metabolic diseases., (© 2024 Usha Satheesan et al.)

Purpose: Preventing metastases by using perioperative interventions has not been adequately explored. Local anesthesia blocks voltage-gated sodium channels and thereby prevents activation of prometastatic pathways. We conducted an open-label, multicenter randomized trial to test the impact of presurgical, peritumoral infiltration of local anesthesia on disease-free survival (DFS)., Methods: Women with early breast cancer planned for upfront surgery without prior neoadjuvant treatment were randomly assigned to receive peritumoral injection of 0.5% lidocaine, 7-10 minutes before surgery (local anesthetics [LA] arm) or surgery without lidocaine (no LA arm). Random assignment was stratified by menopausal status, tumor size, and center. Participants received standard postoperative adjuvant treatment. Primary and secondary end points were DFS and overall survival (OS), respectively., Results: Excluding eligibility violations, 1,583 of 1,600 randomly assigned patients were included in this analysis (LA, 796; no LA, 804). At a median follow-up of 68 months, there were 255 DFS events (LA, 109; no LA, 146) and 189 deaths (LA, 79; no LA, 110). In LA and no LA arms, 5-year DFS rates were 86.6% and 82.6% (hazard ratio [HR], 0.74; 95% CI, 0.58 to 0.95; P = .017) and 5-year OS rates were 90.1% and 86.4%, respectively (HR, 0.71; 95% CI, 0.53 to 0.94; P = .019). The impact of LA was similar in subgroups defined by menopausal status, tumor size, nodal metastases, and hormone receptor and human epidermal growth factor receptor 2 status. Using competing risk analyses, in LA and no LA arms, 5-year cumulative incidence rates of locoregional recurrence were 3.4% and 4.5% (HR, 0.68; 95% CI, 0.41 to 1.11), and distant recurrence rates were 8.5% and 11.6%, respectively (HR, 0.73; 95% CI, 0.53 to 0.99). There were no adverse events because of lidocaine injection., Conclusion: Peritumoral injection of lidocaine before breast cancer surgery significantly increases DFS and OS. Altering events at the time of surgery can prevent metastases in early breast cancer (CTRI/2014/11/005228).[Media: see text].

Background: Breast cancer is the most common cancer among females, with an incidence of 6,41,000 cases annually. The genetic makeup of the individuals, ethnicity, geographical location, lifestyle, and BMI are some well-described factors associated with breast cancer. It is well known that pathogenic variants in BRCA1 and BRCA2 are associated with a majority of hereditary breast cancer. Genome-wide association studies (GWAS) have identified more than 80 germline susceptibility loci responsible for hereditary breast cancer., Methods: In the present study, analysis of 94 genes associated with hereditary cancer was performed using next generation sequencing (NGS) in twelve patients having breast cancer and suspected with hereditary association., Results: Four out of twelve (33%) patients harbored pathogenic mutation of the BRCA1 gene. Two patients was identified p. E23Vfs*17 mutation in BRCA1, one patient had p.Glu1580Gln in BRCA1, and a novel frameshift variant p.T1456Ifs*9(c.4367Cdel) in one patient., Conclusion: In the present study, out of four detected mutations in the BRCA1 gene, three were known and one was a novel BRCA1 mutation. It is advised to perform NGS-based genome sequencing to identify the genetic predisposition in breast cancer patients.

Introduction: Surgery is an important component of multimodality treatment in advanced oral cavity cancers. But in low-middle-income countries like India, with limited centres offering complex head and neck surgeries, prolonged waiting times for surgery is a major problem. An increase in waiting times for treatment has been shown to be a negative prognosticator in head and neck cancer and many patients can develop interim progression making them ineligible for radical treatment. We share our preliminary experience of using oral metronomic chemotherapy as a preoperative treatment in patients expecting delay in surgery., Methods: This was a retrospective analysis of case records of patients with resectable Stage III and Stage IV (IVA & IVB) oral cavity cancers who had received preoperative oral metronomic chemotherapy (POMT). The POMT schedule consisted of oral Methotrexate 15 mg/m2 weekly, Celecoxib 200 mg twice daily and Erlotinib 100 mg daily. Clinico-radiological assessments were done prior to surgery using standard response assessment criteria., Results: A total of 68 patients received POMT with a median age of 55 years (range: 34-73 years). Forty-eight (70%) were males, 29 (42%) had carcinoma tongue and majority ( N = 52, 76%) had Stage IVA cancer. Mean duration of POMT administration was 30.45 days (standard deviation: 8.22). Thirty-seven (54%) patients had partial responses and another 23 (34%) had stable disease. Two (3%) had disease progression on POMT. Fifty-eight (85%) underwent surgery after POMT. Margin positive resection was seen in two patients. Half of the patients who received POMT did not experience any toxicity. Grade 3/4 toxicities were seen in four (6%) patients., Conclusions: POMT is a feasible strategy worth considering in cases where there are prolonged waiting times to surgery., Competing Interests: The authors declare that they have no conflicts of interest., (© the authors; licensee ecancermedicalscience.)

Objectives: e-palliative care (PC) is an evolving concept wherein technological interface is used to deliver PC to the patients with advanced cancer at their doorstep. This study aims to find out the level of satisfaction of patients receiving e-palliative homecare (e-PHC) service from a tertiary Cancer Center using the validated e-Palliative Patient Satisfaction Questionnaire -Malayalam (PSQM)., Materials and Methods: In this prospective study, patients/caregivers on home care were given the e - Palliative PSQM by the homecare nurse after the patient had consulted the doctor through e-PHC service. The questionnaire had 15 statements with response graded using Likert scale. Descriptive analysis was performed to compute the distribution of observed responses to obtain the level of satisfaction among patients or caregivers receiving e-PHC service., Results: This study was done among 120 homecare patients whose median age was 69 (62-79) with almost equal prevalence of both genders. Stage 4 malignancy was seen in 107 (89.2%) patients with the commonest being gastrointestinal malignancy (N=34, 28.3%) The mean score of response for General satisfaction, Technical quality, Communication, Financial aspect, Time spent with doctor and Accessibility and convenience were observed as 4.52, 3.92, 4.48, 4.55, 4.52 and 4.49 respectively. The overall satisfaction was found to be 4.39., Conclusion: The overall satisfaction of patients receiving e-PHC service from our Institution is seen to be high. e- palliative care is a feasible option for providing excellent PC in developing countries with limited resources and financial constraints., Competing Interests: There are no conflicts of interest., (© 2022 Published by Scientific Scholar on behalf of Indian Journal of Palliative Care.)

The sizes of filamentous structures in a cell are often regulated for many physiological processes. A key question in cell biology is how such size control is achieved. Here, we theoretically study the length distributions of multiple filaments, growing by stochastic assembly and disassembly of subunits from a limiting subunit pool. Importantly, we consider a chemical switching of subunits (hydrolysis) prevalent in many biofilaments like microtubules (MTs). We show by simulations of different models that hydrolysis leads to a skewed unimodal length distribution for a single MT. In contrast, hydrolysis can lead to bimodal distributions of individual lengths for two MTs, where individual filaments toggle stochastically between bigger and smaller sizes. For more than two MTs, length distributions are also bimodal, although the bimodality becomes less prominent. We further show that this collective phenomenon is connected with the nonequilibrium nature of hydrolysis, and the bimodality disappears for reversible dynamics. Consistent with earlier theoretical studies, a homogeneous subunit pool, without hydrolysis, cannot control filament lengths. We thus elucidate the role of hydrolysis as a control mechanism on MT length diversity., (Copyright © 2021 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Multimedia, being more attention-getting and attention-holding, is a powerful tool for mass awareness creation and is used for intervention among students in many studies. Our aim was to see the effectiveness of an educational short film in tobacco awareness generation and to compare it with the traditional lecture-based awareness. Selected schools were divided into two groups as per convenience. Short film was used as intervention in Group 1 and PowerPoint-based lecture in Group 2. The increase in awareness was assessed by a pre and posttest. On analysis, though both methods increased awareness as given by higher posttest score, it is found that the awareness levels showed a statistically significant difference between educational short film on hazards of tobacco and power point-based lecture using Mann-Whitney test. Our study proves that an educational short film carefully scripted and picturized can be used effectively in imparting awareness in school-based tobacco control programs., Competing Interests: None

Despite a rapid turnover of subunits, how cells control the lengths of cytoskeletal filaments (such as microtubules) is a fundamental question in cell biology. Here, we theoretically investigate how microscopic processes affect the length distributions of multiple microtubules growing stochastically in a shared subunit pool. In particular, we consider length-dependent positive feedback on filament growth and the chemical conversion from GTP-tubulin to GDP-tubulin (hydrolysis) inside a filament. We found different dynamical regimes for a single filament by simulating a model of microtubule kinetics, where both bimodal and unimodal (bell-shaped) length distributions emerge in the steady state. More significantly, the length distributions of multiple filaments were not unimodal, predicting a collective effect for more than one filament. Interestingly, when length distributions were bimodal, we also observed bistable toggling of individual lengths. Therefore, regulation of biophysical parameters (e.g., hydrolysis rate and feedback strength) can lead to length diversity in an ensemble of multiple microtubules.

Background Tuberculosis (TB) and cancer can coexist in some patients especially from low- and middle-income countries. Impact of active TB on treatment decisions in cancer is less well studied. Methods A retrospective case record review of all cases of cancer diagnosed and or treated between January 2012 and December 2019 who were also diagnosed to have active TB (pulmonary or extrapulmonary) was done. Results Any delay or change in standard treatment of cancer because of active TB or its treatment was noted. Among a total of 32,509 cancer cases, 56 (0.17%) patients were diagnosed to have active TB. Twenty six patients (46%) had delay in starting treatment or delay during cancer treatment. Six (11%) patients were changed from curative treatment option to palliative intent (either best supportive care or palliative Radiation) or no further treatment. Three (5%) patients required change from one type of curative treatment modality to another curative option. Conclusion Eleven percent of patients had to be changed from curative intent to palliative treatment or no further treatment, TB being either the direct or indirect cause in all of them. A nationwide data registry of cancer patients with TB, involving multiple centers, should be considered so that specific problems in this context can be identified and addressed in larger details., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Context: The therapeutic role of D2 lymphadenectomy in the management of gastric cancer is an ongoing controversy., Aims: To examine the morbidity and oncological outcomes of D2 lymph node dissection for gastric cancer patients treated in a stand-alone cancer center in rural India and to compare it with international data., Settings and Design: Retrospective study on patients treated for gastric cancer from June 2009 to December 2014., Methods and Material: All patients underwent subtotal or total gastrectomy with modified D2 lymph node dissection preserving spleen and pancreas. The Clavien-Dindo model was used to stratify the severity of morbidity., Statistical Analysis: Descriptive statistics was used for data exploration. Chi-square test was used to compare the association of various factors with survival. Kaplan-Meier method was used to calculate the survival rates (RFS and DFS). Log-rank test was used to compare the survival of different subgroups., Results: Fifty-four patients (41 males and 13 females) were included in the study. Four (7.4%) patients had significant postoperative morbidity. The 5-year OS and DFS respectively were 34.9% and 37.6%. Female sex was associated with poorer survival. Lymph node ratio of more than 0.2 and advanced stage at presentation showed strong tendency towards lower OS and DFS., Conclusions: An R0 resection with D2 lymphadenectomy for gastric cancer carries acceptable morbidity and mortality in Indian patients with survival rates comparable with the western studies. Lymph node ratio more than 0.2 and female gender and advanced stage were associated with poorer oncological outcomes., Competing Interests: Conflict of InterestThe authors declare that they have no conflict of interest., (© Indian Association of Surgical Oncology 2020.)

Background: Concurrent chemoradiation is the treatment of choice for laryngeal-pharyngeal cancers. Apart from survival organ preservation remains major aims of the treatment. Advanced radiation techniques like VMAT have shown to reduce morbidity. The purpose of our study is to assess the late toxicities in patients treated with concurrent chemoradiation and its association with dose to organs at risk., Aims: Assessment of late toxicities following concurrent chemoradiation in patients with laryngopharyngeal cancers., Materials and Methods: Retrospective study at a tertiary cancer centre on patients with laryngeal and pharyngeal cancers treated with concurrent chemoradiation with VMAT upto a total dose of 69.3 -70 Gy in 33-35 fractions and concurrent chemotherapy with Cisplatin was done. Severe late toxicities and its association with demographic and clinical parameters and dose to OAR were studied. Data was analysed using EpiData analysis v2.2.2.182., Results: Of the 93 patients studied majority were males above 55 years. Oropharynx was the commonest site (58%) with T3 and N2 in majority. Late dysphagia and odynophagia was seen in 18(21%) and 23(27%) patients respectively. 16 (17%) had tube dependence and nine (9.6%) had aspiration pneumonia. D60, V50 and V60 along with site, node positivity and weight loss were found to be significantly associated with severe late toxicity., Conclusion: Oropharyngeal cancers, node positivity and weight loss were found to have significant grade III and above toxicities including tube dependency. Dose to larynx showed association with severe late toxicities, though dose to constrictors could not., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 The South Asian Journal of Cancer.)

Introduction: Community based programs can assist in early detection and improved survival of breast cancer., Aims: To assess the feasibility and explore challenges of a district-wide door-to-door breast cancer screening program "ASWAS" conducted in Kannur district, Kerala, India from 2011 to 2014. METHODS: Aggregate data from survey records were collected in terms of the population screened, referred, diagnosed, and treated. Case records of breast cancer patients who were identified were reviewed and updated. In-depth interviews were conducted with program stakeholders. The contents of the interview were organized into a strength, weakness, opportunity and threat (SWOT) matrix to describe the screening program., Results: A total of 1,049,410 eligible women above 30 years residing in 81 panchayats were visited door-to-door by 8,200 community volunteers; of them, 93% were screened using a symptom-risk factor checklist. Of those referred with symptoms (n = 5353), 81% attended the cancer camp. In total, 23 breast cancer cases were confirmed. 14 (61%) were in early stages, treated, and are disease free at 3-year follow-up. Those in the advanced stage and old age had poor outcomes. SWOT analysis identified political support, female volunteers, community engagement, dedicated fund for treatment, and teamwork as strengths. Weaknesses included poor healthcare access, maintaining volunteer motivation, and issues around sustainability., Conclusion: Community participation with the engagement of the health system and local self-government are required for implementing a comprehensive cancer screening strategy. Breast-cancer screening program using local volunteers for early detection is feasible in low-income settings, thereby improving survival., Competing Interests: None

Partial sacrectomy is a radical procedure that benefits a select group of patients with locally advanced primary or recurrent rectal cancer with posterior extension and carries potential for significant morbidity. This study was done to evaluate the morbidity and oncological outcome of patients who underwent partial sacral resection for rectal cancer in a tertiary cancer center. Seventeen patients underwent partial sacrectomy during the period from 2011 to 2015. Eleven patients had primary and six had recurrent rectal cancer. All patients were evaluated with MRI pelvis and metastatic evaluation with CT scan of the chest and abdomen and PET scan in patients with recurrent cancer. All patients had resection below the level of S2/S3 junction or lower. Three patients were females and the remaining were males. Median age was 56 years. Overall morbidity was 76% and most common morbidity was wound related. The mean estimated relapse-free survival (RFS) for patients treated for primary rectal cancer was 20.3 months (95% confidence interval (CI), 12.8-27.9) and the mean estimated overall survival (OS) 23.9 months. Estimated mean RFS for patients who were operated for recurrent rectal cancer was 25.6 months (95% CI, 17.7-33.5) and the median RFS was yet to reach. Estimated mean OS was 29.7 months (95% CI, 15.5-43.8) and the median OS was 39.6 months. Partial sacrectomy below the level of S2/S3 junction is a safe approach to facilitate en bloc resection of locally advanced primary and recurrent rectal cancer extending posteriorly with loss of plane with sacrum. In selected patients, this approach can improve survival at the cost of high morbidity.

Background: Oral cancer is very common in India. The reported 5-year survival of such patients is around 50% after treatment with surgery and radiotherapy, much lower than most of the developed countries., Methods: A retrospective study of a prospective database of oral cancer patients undergoing surgery from June 2009 to June 2013 was conducted. Follow-up details were updated from case records and by phone calls. Data were double entered in EpiData Entry version 3.1 and were analysed using EpiData Analysis software 2.1.0.73., Results: Two-hundred and twenty patients were analysed (136 males); 85% were consuming tobacco, mainly in chewable form. The majority (51.1%) had tongue cancer, of whom 75 patients (34.1%) had T4 tumours. Postoperative radiotherapy was given to 108 patients (49.1%). Forty had recurrence, of which 23 were in early stage. Of these, 19 showed node positivity (p < 0.01). Node-negative patients had 79% 5-year survival while node positive had 59% which is comparable to that reported in developed countries. Median disease-free survival duration was 48.2 months., Conclusions: Node positivity is the single factor affecting recurrence and survival. The overall survival and disease-free survival is better in patients without lymph node involvement and in patients with early stage of cancer as compared to the patients with node involvement and in advanced stages.

Ethical regulations and technical challenges for research in human pathology, immunology, and therapeutic development have placed small animal models in high demand. With a close genetic and behavioral resemblance to humans, small animals such as the mouse are good candidates for human disease models, through which human-like symptoms and responses can be recapitulated. Further, the mouse genetic background can be altered to accommodate diverse demands. The NOD/SCID/IL2rγ null (NSG) mouse is one of the most widely used immunocompromised mouse strains; it allows engraftment with human hematopoietic stem cells and/or human tissues and the subsequent development of a functional human immune system. This is a critical milestone in understanding the prognosis and pathophysiology of human-specific diseases such as HIV/AIDS and aiding the search for a cure. Herein, we report a detailed protocol for generating a humanized NSG mouse model (hu-NSG) by hematopoietic stem cell transplantation into a radiation-conditioned neonatal NSG mouse. The hu-NSG mouse model shows multi-lineage development of transplanted human stem cells and susceptibility to HIV-1 viral infection. It also recapitulates key biological characteristics in response to combinatorial antiretroviral therapy (cART).

Introduction: Charlson comorbidity index (CCI) is a validated tool enabling clinicians for prediction of adverse events posttherapy. In this study, we planned to estimate the predictive value of age-adjusted CCI (ACCI) in assessing the perioperative complication in oncological patients undergoing major pelvic surgeries., Methods: This was a single arm, prospective, observational study, in which adult patients with pelvic malignancies undergoing pelvic surgeries were selected. The relationship between the ACCI and Grade 3-5 adverse events were tested using Fisher's test., Results: The rate of Grade 3-5 adverse event rate was 16.7% (11 patients, n = 66). Among the whole cohort, 11 patients (16.7%) had high score on ACCI. The rate of Grade 3-5 adverse events was higher in the cohort of patients with high ACCI score (45.5% vs. 10.9%, P = 0.014). The sensitivity, specificity and negative and positive predictive values were 45.5%, 89.1%, 89.1%, and 45.5%, respectively., Conclusion: ACCI can predict for postsurgical adverse events. It has a high negative predictive value for nonoccurrence of adverse events., Competing Interests: There are no conflicts of interest.

Background: Oral cancer is a major public health challenge, and about one-fifth of all oral cancer cases reported globally are from India. In spite of the potential for early detection by simple visual examination, the majority of patients report in later stages of the disease, especially in low and middle-income countries. We report the results from a district level population-based oral cancer screening program., Methods: A cross-sectional survey was carried out among people aged >15 years in 48 panchayats of Kannur district in Kerala, India. This comprehensive multi-stakeholder district-wide screening was carried out in six stages including planning, sensitization, recruiting of community volunteers and training, survey, organization of specialist camps and referring to cases to cancer center. The descriptive statistical analysis was performed using EpiData analysis software (Version 2.2.2.180)., Results: Among the 1,061,088 people in 265,272 houses surveyed, 2507 of them attended the screening camps, and 13 oral cancers and 174 oral precancers were detected. Majority of the oral cancer patients were male (69%), with primary education or illiterate (62%) and low socioeconomic status (61%). Five of the patients diagnosed with early-stage cancer are alive and have good oral health-related quality of life., Conclusion: Detection of precancerous and early-stage cancers should be a priority of oral cancer screening programs. The possible key for addressing cancer screening needs of the rural population is to equip the primary health centers in cancer screening activities with available human resources while adapting to local context., Competing Interests: There are no conflicts of interest.

In regenerative medicine, despite the chances of graft-rejection, scaffolds prepared from extracellular matrices of various mammalian organs/tissues are widely used. Graft-assisted healing of full thickness skin-wounds is a major use of these bioscaffolds. Therefore, considering its prospective clinical use as a wound healing matrix, this study evaluated the healing potential of porcine cholecyst-derived scaffold (CDS) prepared by a non-detergent/enzymatic method for treating naturally occurring full thickness lacerated wounds in dogs. The CDS caused, in comparison with a commercial-grade bioscaffold prepared out of bovine dermal collagen (BDC), faster healing with respect to the wound healing parameters like peripheral tissue oedema, necrosis (amount and type), indurations, granulation tissue formation and the extent of re-epithelialisation. After 28 days of the treatment, the wound area (mean + SE) reduced from 27.60 ± 8.96 cm 2 to 0.19+ 0.18 cm 2 and 21.39 ± 5.48 to 6.59 ± 2.60 cm 2 in CDS and BDC treated animals, with a reduction in wound sizes by 98.95 ± 2.09% and 54.53 ± 15.90 respectively. By this time, complete wound healing was observed in at least 75% of the former and 25% of the later groups. The CDS was deemed as a candidate bioscaffold for treating full thickness lacerated skin wounds in dogs.

Although current combinatorial antiretroviral therapy (cART) is therapeutically effective in the majority of HIV patients, interruption of therapy can cause a rapid rebound in viremia, demonstrating the existence of a stable reservoir of latently infected cells. HIV latency is therefore considered a primary barrier to HIV eradication. Identifying, quantifying, and purging the HIV reservoir is crucial to effectively curing patients and relieving them from the lifelong requirement for therapy. Latently infected transformed cell models have been used to investigate HIV latency; however, these models cannot accurately represent the quiescent cellular environment of primary latently infected cells in vivo For this reason, in vivo humanized murine models have been developed for screening antiviral agents, identifying latently infected T cells, and establishing treatment approaches for HIV research. Such models include humanized bone marrow/liver/thymus mice and SCID-hu-thy/liv mice, which are repopulated with human immune cells and implanted human tissues through laborious surgical manipulation. However, no one has utilized the human hematopoietic stem cell-engrafted NOD/SCID/IL2rγ null (NSG) model (hu-NSG) for this purpose. Therefore, in the present study, we used the HIV-infected hu-NSG mouse to recapitulate the key aspects of HIV infection and pathogenesis in vivo Moreover, we evaluated the ability of HIV-infected human cells isolated from HIV-infected hu-NSG mice on suppressive cART to act as a latent HIV reservoir. Our results demonstrate that the hu-NSG model is an effective surgery-free in vivo system in which to efficiently evaluate HIV replication, antiretroviral therapy, latency and persistence, and eradication interventions. IMPORTANCE HIV can establish a stably integrated, nonproductive state of infection at the level of individual cells, known as HIV latency, which is considered a primary barrier to curing HIV. A complete understanding of the establishment and role of HIV latency in vivo would greatly enhance attempts to develop novel HIV purging strategies. An ideal animal model for this purpose should be easy to work with, should have a shortened disease course so that efficacy testing can be completed in a reasonable time, and should have immune correlates that are easily translatable to humans. We therefore describe a novel application of the hematopoietic stem cell-transplanted humanized NSG model for dynamically testing antiretroviral treatment, supporting HIV infection, establishing HIV latency in vivo The hu-NSG model could be a facile alternative to humanized bone marrow/liver/thymus or SCID-hu-thy/liv mice in which laborious surgical manipulation and time-consuming human cell reconstitution is required., (Copyright © 2018 American Society for Microbiology.)

Gene-based therapies represent a promising therapeutic paradigm for the treatment of HIV-1, as they have the potential to maintain sustained viral inhibition with reduced treatment interventions. Such an option may represent a long-term treatment alternative to highly active antiretroviral therapy. Methods: We previously described a therapeutic approach, referred to as transcriptional gene silencing (TGS), whereby small noncoding RNAs directly inhibit the transcriptional activity of HIV-1 by targeting sites within the viral promoter, specifically the 5' long terminal repeat (LTR). TGS differs from traditional RNA interference (RNAi) in that it is characterized by concomitant silent-state epigenetic marks on histones and DNA. To deliver TGS-inducing RNAs, we developed functional RNA conjugates based on the previously reported dual function of the gp120 (A-1) aptamer conjugated to 27-mer Dicer-substrate anti-HIV-1 siRNA (dsiRNA), LTR-362. Results: We demonstrate here that high levels of processed guide RNAs localize to the nucleus in infected T lymphoblastoid CEM cell line and primary human CD4+ T-cells. Treatment of the aptamer-siRNA conjugates induced TGS with an ~10-fold suppression of viral p24 levels as measured at day 12 post infection. To explore the silencing efficacy of aptamer-siRNA conjugates in vivo , HIV-1-infected humanized NOD/SCID/IL2 rγ null mice (hu-NSG) were treated with the aptamer-siRNA conjugates. Systemic delivery of the A-1-stick-LTR-362 27-mer siRNA conjugates suppressed HIV-1 infection and protected CD4+ T cell levels in viremia hu-NSG mice. Principle conclusions: Collectively these data suggest that the gp120 aptamer-dsiRNA conjugate design is suitable for systemic delivery of small RNAs that can be used to suppress HIV-1., Competing Interests: Conflict of Interest: J. J. R. and J. Z. have an issued patent entitled “Cell-type specific aptamer-siRNA delivery system for HIV-1 therapy”. USPTO, No. US 8, 222, 226 B2, issued date: July 17, 2012. J.J.R., J. Z., M.S.W and K.V.M. have an issued patent entitled “Cell-specific internalizing RNA aptamers against human CCR5 and used therefore”, USPTO, No. US 9,605,266, issued date: March 28, 2017.

Fishes are equipped to sense stressful stimuli and are able to respond to environmental stressor such as hypoxia with varying pattern of stress response. The functional attributes of brain to hypoxia stress in relation to ion transport and its interaction during immune challenge have not yet delineated in fish. We, therefore, explored the pattern of ion transporter functions and messenger RNA (mRNA) expression of α1-subunit isoforms of Na + /K + -ATPase (NKA) in the brain segments, namely, prosencephalon (PC), mesencephalon (MC), and metencephalon (MeC) in an obligate air-breathing fish exposed either to hypoxia stress (30 minutes forced immersion in water) or challenged with zymosan treatment (25-200 ng g -1 for 24 hours) or both. Zymosan that produced nonspecific immune responses evoked differential regulation of NKA, H + /K + -ATPase (HKA), and [Formula: see text] (NNA) in the varied brain segments. On the contrary, hypoxia stress that demanded activation of NKA in PC and MeC showed a reversed NKA activity pattern in MeC of immune-challenged fish. A compromised HKA and NNA regulation during hypoxia stress was found in immune-challenged fish, indicating the role of these brain ion transporters to hypoxia stress and immune challenges. The differential mRNA expression of α1-subunit isoforms of NKA, nkaα1a , nkaα1b , and nkaα1c , in hypoxia-stressed brain showed a shift in its expression pattern during hypoxia stress-immune interaction in PC and MC. Evidence is thus presented for the first time that ion transporters such as HKA and NNA along with NKA act as functional brain markers which respond differentially to both hypoxia stress and immune challenges. Taken together, the data further provide evidence for a differential Na + , K + , H + , and [Formula: see text] ion signaling that exists in brain neuronal clusters during hypoxia stress-immune interaction as a result of modified regulations of NKA, HKA, and NNA transporter functions and nkaα1 isoform regulation., Competing Interests: Declaration of conflicting interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Cancer cervix is the second common cause of cancer death in India. It is the most curable form of any human cancer if detected at the precancerous stage. Although several factors determine the survival of the disease, the clinical stage at presentation is the single most important predictor of long-term survival. The present study aimed to describe the performance and follow-up status and 5-year survival experience of the cervical cancer patients registered between 2010 and 2011 by the hospital registry of Malabar Cancer Centre, Kerala, and factors affecting lost to follow-up and survival among them. The case sheets of 227 patients retrospectively scrutinized during May-July 2014. The mean age of patients was 58.8 years (standard deviation = 11.67 years). The majority of the patients completed the initially planned treatment, but a low proportion of patients were likely to be on regular follow-up. This study revealed that most of the patients registered at the hospital only at an advanced stage. Using Kaplan-Meier method, the estimated 5 years survival rate was found to be 66.8%. It was noted that performance status before treatment and Federation of Gynecology and Obstetrics staging were significantly associated with lost to follow-up and survival rate majority of the cervical cancer patients are observed to be highly noncomplaint to complete treatment and on follow-up. Thus, these findings stress the importance of counseling family members regarding the importance of follow-up and formulating public health policies aimed at increasing the awareness and implementation of cervical cancer screening programs in North Malabar.

Background: Addition of erlotinib to metronomic chemotherapy (MCT) may lead to further improvement in progression-free survival (PFS) and overall survival in head and neck cancers. The aim of this study was to study the PFS with MCT + erlotinib combination in our setting., Methods: A single-arm prospective observational study conducted at Malabar Cancer Center. Patients warranting palliative chemotherapy for head and neck cancers, having adequate organ function, not-affording cetuximab and not willing for intravenous chemotherapy were included in this study. Oral methotrexate (15 mg/m(2)/week), oral celecoxib (200 mg twice daily), and erlotinib (150 mg once daily) were administered till the progression of the disease or till intolerable side-effects. Patients underwent toxicity (CTCAE version 4.02) and response (RECIST version 1.1) assessment every 30 days. Statistical analysis was performed using SPSS version 16 (IBM, New York, USA). Descriptive statistics and Kaplan-Meier analysis have been performed., Results: A total of 15 patients received MCT. The median age of these patients was 65 years (range: 48-80). The Eastern Cooperative Oncology Group Performance Status was 0-1 in seven patients (46.7%), while it was 2 in eight patients (53.3%). The primary sites of tumor were predominantly oral cavity, 11 (73.4%). Prior to MCT, treatment with palliative radiation therapy was given in 11 patients and curative treatment in two patients. The best response post-MCT was complete remission in two patients, partial remission in seven patients, stable disease in four patients, and progressive disease in two patients. The median estimated PFS was 148 days (95% confidence interval 95.47-200.52 days). For a median follow-up of 181 days, there were only three deaths. Grade 3-4 toxicity was seen in six patients (40%). Dose reduction was required in four patients (26.7%)., Conclusion: The addition of erlotinib to an MCT schedule of methotrexate and celecoxib resulted in a promising PFS and should be tested in future studies.

Introduction: Malignancy leading to a hypercoagulable state is a well established concept. The reported frequency of venous thrombotic events in cancer patients is 5-8%. There is limited data on the influence of thrombosis on treatment decisions in solid tumors., Methods: A retrospective audit of all cases of thrombosis developing in newly diagnosed solid tumors from 1st January 2011 to 31st December 2014 was performed. Changes in treatment decisions for malignancy (deferral of surgery/chemotherapy, changes in the planned course of chemotherapy or changes in the planned dates of chemotherapy) after the documentation of thrombosis were noted., Results: A total of 11,796 solid tumor cases were registered. 61 patients with thrombosis (0.52%) were identified. In 14 patients(23%), treatment decisions for malignancy had to be changed after the occurrence of thrombosis. 2 patients were deferred surgery, 9 could not undergo chemotherapy according to planned schedules, and 3 were deferred chemotherapy. In survival analysis by multivariate model, stage (p=0.01) and ECOG performance status (p=0.01) significantly predicted survival whereas thrombus location (p=0.09), symptomatic thrombosis (p=0.06), and age (p=0.19) did not., Conclusions: Frequency of thrombosis in solid tumors in our centre was less compared to previous reports. There was a significant deviation (nearly one fourth patients) from standard of treatment for malignancy after the development of thrombosis. Survival of patients who developed thrombosis did not significantly vary depending on location of thrombosis or whether it is symptomatic or not., (Copyright © 2015 Elsevier Ltd. All rights reserved.)