Phage therapy for Acinetobacter baumannii infection.

Acinetobacter is a gram-negative nosocomial pathogenic bacteria. The contributing factor for the pathogenicity of Acinetobacter is severe due to its property of antibacterial drug resistance. Often antibiotic treatment is used to treat bacterial infection, however due to the resistance of a broad range of antibiotics by Acinetobacter the treatment viability of this bacterial species seems to be reduced. To combat this diverse treatment options are being incorporated with phage therapy being an effective choice due to its intrinsic property to infect bacteria. In this chapter the various phage therapy used in recent times has been elaborated on. The phage therapy is considered to be in response to Carbapenem resistance. The various mode of phage propagation has been mentioned in this chapter along with the type of resistance conferred to the administered therapy. The chapter deals with the advances observed due to therapy of Acibel004, Acibel007, vB-GEC_Ab-M-G7, ZZ1 and Bacteriophage p54 containing Endolysin LysAB54 bacteriophages have been elucidated.

Long-term outcomes and prognostic factors in elderly patients with breast cancer: single-institutional experience.

Introduction: Despite advances in treatment, there is rising mortality in elderly patients with breast cancer. We aimed to conduct an audit of non-metastatic elderly breast cancer patients to understand the predictors of outcome. Methods: Data collection was done from electronic medical records. All time-to-event outcomes were analysed using Kaplan-Meier method and compared using log-rank test. Univariate and multi-variate analysis of known prognostic factors was also done. Any p-value ≤0.05 was considered statistically significant. Results: A total of 385 elderly (>70 years) breast cancer patients (range 70-95 years) were treated at our hospital from January 2013 to December 2016. The hormone receptor was positive in 284 (73.8%) patients; 69 (17.9%) patients had over-expression of HER2-neu, while 70 (18.2%) patients had triple-negative breast cancer. A large majority of women (N = 328, 85.9%) underwent mastectomy while only 54 (14.1%) had breast conservation surgery. Out of 134 patients who received chemotherapy, 111 patients received adjuvant, while the remaining 23 patients received neoadjuvant chemotherapy. Only 15 (21.7%) patients of the 69 HER2-neu receptor-positive patients received adjuvant trastuzumab. Adjuvant radiation was given to 194 (50.3%) women based on the type of surgery and disease stage. Adjuvant hormone therapy was planned using letrozole in 158 (55.6%) patients, while tamoxifen was prescribed in 126 (44.4%). At the median follow up of 71.7 months, the 5-year overall survival, relapse-free survival, locoregional relapse-free survival, distant disease-free survival, breast cancer-specific survival were 75.3%, 74.2%, 84.8%, 76.1% and 84.5%. Age, tumour size, presence of lymphovascular invasion (LVSI) and molecular subtype emerged as independent predictors of survival on multi-variate analysis. Conclusion: The audit highlights the underutilisation of breast-conserving therapy and systemic therapy in the elderly. Increasing age and tumour size, presence of LVSI and molecular subtype were found to be strong predictors of outcome. The findings from this study will help to improve the current gaps in the management of breast cancer among the elderly.

COVID-19 phase 4 vaccine candidates, effectiveness on SARS-CoV-2 variants, neutralizing antibody, rare side effects, traditional and nano-based vaccine platforms: a review.

The COVID-19 pandemic has endangered world health and the economy. As the number of cases is increasing, different companies have started developing potential vaccines using both traditional and nano-based platforms to overcome the pandemic. Several countries have approved a few vaccine candidates for emergency use authorization (EUA), showing significant effectiveness and inducing a robust immune response. Oxford-AstraZeneca, Pfizer-BioNTech's BNT162, Moderna's mRNA-1273, Sinovac's CoronaVac, Johnson & Johnson, Sputnik-V, and Sinopharm's vaccine candidates are leading the race. However, the SARS-CoV-2 is constantly mutating, making the vaccines less effective, possibly by escaping immune response for some variants. Besides, some EUA vaccines have been reported to induce rare side effects such as blood clots, cardiac injury, anaphylaxis, and some neurological effects. Although the COVID-19 vaccine candidates promise to overcome the pandemic, a more significant and clear understanding is needed. In this review, we brief about the clinical trial of some leading candidates, their effectiveness, and their neutralizing effect on SARS-CoV-2 variants. Further, we have discussed the rare side effects, different traditional and nano-based platforms to understand the scope of future development.

Assessment of Prevalence of Recurrent Aphthous Stomatitis in the North Indian Population: A Cross-Sectional Study.

AIM AND OBJECTIVE: The present study was undertaken for assessing the prevalence of recurrent aphthous stomatitis (RAS) in the North Indian population. MATERIALS AND METHODS: Assessment of a total of 4255 patients was done over a period of 2 years, who came for a routine dental checkup. Recording of the complete demographic and clinical details of all the patients was done. The prevalence of RAS was assessed. Profile of patients with RAS was assessed separately. A pro forma was made and the type of treatment protocol followed by patients with RAS was also recorded. All the results were recorded in a Microsoft Excel sheet and were analyzed using SPSS software. RESULTS: Analysis of a total of 4255 patients was done. RAS was found to be present in 800 patients. The overall prevalence of RAS was found to be 18.93%. Significant results were obtained when analyzing age, gender, and occupation as risk factors for RAS. Labial/buccal mucosa involvement occurred in 51.875% of the cases. In 44% of the cases, the size of the RAS was between 1 cm and 3 cm. Home remedy was followed in 17.875% of the cases. CONCLUSION: A significant proportion of patients in the North Indian population is affected by RAS. In comparison to males, females are more commonly affected.

Mandibular Ramus as a Strong Expressor of Sex Determinations: A Digital Radiographic Study.

BACKGROUND: This study aimed to assess the effectiveness of mandibular ramus in gender identification in Haryana population. MATERIALS AND METHODS: One hundred patients were assessed. Panoramic radiological examination was done. Following parameters were recorded: MAX. RM. WDTH (Maximum ramus breadth), MIN. RM. WDTH (Minimum ramus breadth), CND. HGT. RM (Condylar height), PRJ. HGT. RM (Projective height of the ramus), and CRND. HGT. RM (Coronoid height). All the results were recorded in Microsoft excel sheet and were analyzed by SPSS software version 16.0. RESULTS: There is significant difference found in males and females in maximum ramus width, minimum ramus width, condylar height, and coronoid height and between male and females in condylar height and coronoid height. Furthermore, there was statistical significant difference between male and females in coronoid height. CONCLUSION: Mandibular ramus can be used for gender assessment as a part of forensic investigation.

Dentinogenesis imperfecta type II: Diagnosis, functional and esthetic rehabilitation in mixed dentition.

Dentinogenesis imperfecta (DGI) type II affects both primary and permanent dentitions and has the autosomal mode of inheritance. The affected teeth may appear as amber or gray because of chipping of enamel shortly after their eruption. Correct diagnosis and management are highly needed to restore the quality of oral health and to improve esthetics and masticatory functions. We present here a case of systematic and conservative dental approach in the management of a 7-year-old child having Dentinogenesis Imperfecta Type II (DGI Type II) with 1 ½ follow-up.

One-pot mild and efficient synthesis of [1,3]thiazino[3,2-a]indol-4-ones and their anti-proliferative activity.

A base mediated environmentally benign one-pot efficient methodology has been developed for the synthesis of [1,3]thiazino[3,2-a]indol-4-ones using indoline-2-thiones and propiolate esters in aqueous medium. The conjugate addition of thiones first results in ethyl (3-(indol-2-yl)thio)acrylates in situ, which subsequently undergoes intramolecular cyclization to produce indole-fused thiazin-4-ones in good to excellent yields. The cytotoxic screening of the synthesized compounds using MTT assay revealed the anti-proliferative nature of these frameworks against triple negative breast cancer cell lines with the highest activity emanating from 4H-[1,3]thiazino[3,2-a]indol-4-one and 8-methyl-2-propyl-4H-[1,3]thiazino[3,2-a]indol-4-one compounds.

Multinucleated polyploidy drives resistance to Docetaxel chemotherapy in prostate cancer.

BACKGROUND: Docetaxel is the only FDA-approved first-line treatment for castration-resistant prostate cancer (CRPC) patients. Docetaxel treatment inevitably leads to tumour recurrence after an initial therapeutic response with generation of multinucleated polyploid (MP) cells. Here we investigated role of MP cells in clinical relapse of CRPC. METHODS: Prostate cancer (PC-3) cells were treated with docetaxel (5 nM) for 3 days followed by a washout and samples were collected at close intervals over 35 days post drug washout. The tumorigenic potential of the giant MP cells was studied by implanting MP cells subcutaneously as tumour xenografts in nude mice. RESULTS: Docetaxel-induced polyploid cells undergo mitotic slippage and eventually spawn mononucleated cells via asymmetric cell division or neosis. Both MP and cells derived from polyploid cells had increased survival signals, were positive for CD44 and were resistant to docetaxel chemotherapy. Although MP cells were tumorigenic in nude mice, these cells took a significantly longer time to form tumours compared with parent PC-3 cells. CONCLUSIONS: Generation of MP cells upon docetaxel therapy is an adaptive response of apoptosis-reluctant cells. These giant cells ultimately contribute to the generation of mononucleated aneuploid cells via neosis and may have a fundamental role precipitating clinical relapse and chemoresistance in CRPC.

A centrosome clustering protein, KIFC1, predicts aggressive disease course in serous ovarian adenocarcinomas.

BACKGROUND: Amplified centrosomes are widely recognized as a hallmark of cancer. Although supernumerary centrosomes would be expected to compromise cell viability by yielding multipolar spindles that results in death-inducing aneuploidy, cancer cells suppress multipolarity by clustering their extra centrosomes. Thus, cancer cells, with the aid of clustering mechanisms, maintain pseudobipolar spindle phenotypes that are associated with low-grade aneuploidy, an edge to their survival. KIFC1, a nonessential minus end-directed motor of the kinesin-14 family, is a centrosome clustering molecule, essential for viability of extra centrosome-bearing cancer cells. Given that ovarian cancers robustly display amplified centrosomes, we examined the overexpression of KIFC1 in human ovarian tumors. RESULTS: We found that in clinical epithelial ovarian cancer (EOC) samples, an expression level of KIFC1 was significantly higher when compared to normal tissues. KIFC1 expression also increased with tumor grade. Our In silico analyses showed that higher KIFC1 expression was associated with poor overall survival (OS) in serous ovarian adenocarcinoma (SOC) patients suggesting that an aggressive disease course in ovarian adenocarcinoma patients can be attributed to high KIFC1 levels. Also, gene expression levels of KIFC1 in high-grade serous ovarian carcinoma (HGSOC) highly correlated with expression of genes driving centrosome amplification (CA), as examined in publically-available databases. The pathway analysis results indicated that the genes overexpressed in KIFC1 high group were associated with processes like regulation of the cell cycle and cell proliferation. In addition, when we performed gene set enrichment analysis (GSEA) for identifying the gene ontologies associated to KIFC1 high group, we found that the first 100 genes enriched in KIFC1 high group were from centrosome components, mitotic cell cycle, and microtubule-based processes. Results from in vitro experiments on well-established in vitro models of HGSOC (OVSAHO, KURAMOCHI), OVCAR3 and SKOV3) revealed that they display robust centrosome amplification and expression levels of KIFC1 was directly associated (inversely correlated) to the status of multipolar mitosis. This association of KIFC1 and centrosome amplification with HGSOC might be able to explain the increased aggressiveness in this disease. CONCLUSION: These findings compellingly underscore that KIFC1 can be a biomarker that predicts an aggressive disease course in ovarian adenocarcinomas.

Malignant fibrous histiocytoma of maxillary sinus- a diagnostic challenge.

Malignant fibrous histiocytoma (MFH) is a malignant mesenchymal tumor uncommonly seen in head and neck region and even rarer in maxillary sinus with less than thirty cases reported in literature. Microscopic diagnosis at this rare site may be challenging because of the spectrum of features, which frequently overlap with other benign and malignant tumors. We herein report a case of malignant fibrous histiocytoma of the maxillary sinus in a 40-year-old man who presented with epistaxis. The initial biopsy appeared benign whereas histopathology of wide surgical excision was consistent with MFH. In view of the deep location, the diagnosis may be missed on a small biopsy, which can appear deceptive leading to diagnostic errors. This case report highlights the histopathological difficulties and pitfalls of this tumor at this rare site.

Bilateral invasive duct carcinoma, phyllodes tumor and multiple fibroadenomas of breast associated with lymph node metastases - rare coexistence.

Concomitant occurrence of phyllodes tumor with an in situ or invasive carcinoma in the breast is an uncommon phenomenon and has been reported sparingly. We describe a rare case of simultaneous bilateral intraductal and infiltrating duct carcinoma with coexisting fibroadenomas and phyllodes tumor. To the best of our knowledge, only 19 cases of invasive carcinoma with phyllodes tumor have been reported so far and lymph node metastases has been described only once. A 43 year-old woman presented with multiple bilateral breast lumps. Core biopsies revealed phyllodes tumor in the right breast and invasive duct carcinoma of the left breast. Simple mastectomy done for right breast showed foci of invasive carcinoma arising in phyllodes tumor. Metastasis was detected in the left axillary lymph nodes. This case is being reported to create awareness of this rare transformation, which has significant prognostic and therapeutic implications.

Primary gastric adenosquamous carcinoma in an Indian male.

Adenosquamous carcinoma (ASC) of the stomach is a very rare tumor comprising less than 0.5% of all stomach malignancies. Here, we report a case of a 37-year-old male, who presented with upper gastrointestinal bleeding in the form of hematemesis and malena. A subtotal gastrectomy was done in view of massive uncontrolled bleed. Histology showed evidence of ASC of the body and antrum with metastasis to the liver, perigastric lymph nodes and peritoneal and pleural cavity.

Synchronous gastric gastrointestinal stromal tumor (GIST) and other primary neoplasms of gastrointestinal tract: report of two cases.

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal neoplasms of the gastrointestinal tract with a malignant potential. However, uncommonly they can be associated with synchronous tumors of different histogenesis. We herein report two cases of gastric GIST with synchronous tumors. The first case is of a 50-year-old male patient who was suspected with GIST of stomach and was incidentally found to have an associated duodenal neuroendo-crine neoplasm. The second case is of a 62-year-old male who, while undergoing surgery for a primary colon adenocarcinoma, was incidentally detected to have a coexistent gastric GIST initially suspected to be a metastatic nodule. Coexistence of gastric GIST with neuroendocrine tumor is extremely rare. To the best of our knowledge this is the second case of gastric GIST coexisting with duodenal neuroendocrine tumor to be reported in the literature. Similarly, association of GIST with adenocarcinoma is uncommon. We herein analyze the pathological findings of two such cases, and we review the malignant potential of these synchronous tumors.

Immunotherapeutic strategies for cancer treatment: a novel protein transfer approach for cancer vaccine development.

Cancer cells have developed numerous ways to escape immune surveillance and gain unlimited proliferative capacity. Currently, several chemotherapeutic agents and radiotherapy, either alone or in combination, are being used to treat malignancies. However, both of these therapies are associated with several limitations and detrimental side effects. Therefore, recent scientific investigations suggest that immunotherapy is among the most promising new approaches in modern cancer therapy. The focus of cancer immunotherapy is to boost both acquired and innate immunity against malignancies by specifically targeting tumor cells, and leaving healthy cells and tissues unharmed. Cellular, cytokine, gene, and monoclonal antibody therapies have progressively become promising immunotherapeutic approaches that are being tested for several cancers in preclinical models as well as in the clinic. In this review, we discuss recent advances in these immunotherapeutic approaches, focusing on new strategies that allow the expression of specific immunostimulatory molecules on the surface of tumor cells to induce robust antitumor immunity.

Stature estimation from foot length using universal regression formula in a North Indian population.

Stature is a significant parameter in establishing identity of an unknown. Conventionally, researchers derive regression formula separately for males and females. Sex, however, may not always be determined accurately, particularly in dismembered remains and thus the need for a universal regression formula for stature estimation irrespective of sex of an individual. The study was carried out in an endogamous group of North India to compare the accuracy of sex-specific regression models for stature estimation from foot length with the models derived when the sex was presumed as unknown. The study reveals that regression equation derived for the latter can estimate stature with reasonable accuracy. Thus, stature can be estimated accurately from foot length by regression analysis even when sex remains unknown.

Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers.

Somatic mutations that activate phosphoinositide 3-kinase (PI3K) have been identified in the p110-alpha catalytic subunit (encoded by PIK3CA). They are most frequently observed in two hotspots: the helical domain (E545K and E542K) and the kinase domain (H1047R). Although the p110-alpha mutants are transforming in vitro, their oncogenic potential has not been assessed in genetically engineered mouse models. Furthermore, clinical trials with PI3K inhibitors have recently been initiated, and it is unknown if their efficacy will be restricted to specific, genetically defined malignancies. In this study, we engineered a mouse model of lung adenocarcinomas initiated and maintained by expression of p110-alpha H1047R. Treatment of these tumors with NVP-BEZ235, a dual pan-PI3K and mammalian target of rapamycin (mTOR) inhibitor in clinical development, led to marked tumor regression as shown by positron emission tomography-computed tomography, magnetic resonance imaging and microscopic examination. In contrast, mouse lung cancers driven by mutant Kras did not substantially respond to single-agent NVP-BEZ235. However, when NVP-BEZ235 was combined with a mitogen-activated protein kinase kinase (MEK) inhibitor, ARRY-142886, there was marked synergy in shrinking these Kras-mutant cancers. These in vivo studies suggest that inhibitors of the PI3K-mTOR pathway may be active in cancers with PIK3CA mutations and, when combined with MEK inhibitors, may effectively treat KRAS mutated lung cancers.

Stature estimation from foot dimensions.

Identification of an individual is the mainstay in forensic investigations. The dimensions of the foot have been used for the determination of sex, age, and stature of an individual. The present study examines the relationship between stature and foot dimensions among Gujjars, a North Indian endogamous group. Stature, foot length and foot breadth of 200 subjects comprising 100 males and 100 females were measured. Statistical analyses indicated that the bilateral variation was insignificant for all the measurements except foot breadth in males (p<0.01). Sex differences were found to be highly significant for all the measurements (p<0.01). Linear and multiple regression equations for stature estimation were calculated using the aforementioned variables and multiplication factors were computed. The correlation coefficients between stature and foot dimensions were found to be positive and statistically highly significant. The highest correlation coefficient between stature and foot length in males and foot breadth in females indicates that the foot length provides the highest reliability and accuracy in estimating stature of an unknown male and foot breadth in a female. Prediction of stature was found to be most accurate by multiple regression analysis.

Increased PAK6 expression in prostate cancer and identification of PAK6 associated proteins.

BACKGROUND: PAK6 is a member of the p21-activated kinase (PAK) family of serine/threonine kinases that was originally cloned from prostate cancer (PCa) cells as an androgen receptor interacting protein, but its cellular distribution and functions have not been established. METHODS: An affinity purified rabbit anti-PAK6 antiserum was generated to assess PAK6 protein expression. PAK6 associated proteins were identified by immunopurification of 3xFlag-tagged PAK6 followed by LC/MS/MS. RESULTS: We confirmed that PAK6 protein is expressed in prostate and breast cancer cell lines. PAK6 expression in LNCaP PCa cells was not directly androgen regulated, but was markedly increased when the cells were cultured for 6-8 weeks in steroid hormone depleted medium. By immunohistochemistry, PAK6 was weakly expressed in normal prostate epithelium. Its expression was increased in primary and metastatic PCa, and was further increased in tumors that relapsed after androgen deprivation therapy. LC/MS/MS identified IQ motif containing GTPase activating protein 1 (IQGAP1) and protein phosphatase 1B (PP1B) as candidate PAK6 interacting proteins, and these findings were confirmed by coimmunoprecipitation. CONCLUSIONS: These results indicate that PAK6 contributes to PCa development and progression after androgen deprivation therapy, and that it may play roles in the regulation of motility and in stress responses.

Foot index: is it a tool for sex determination?

Identification of an individual is of paramount importance in forensic investigations. The dimensions of the foot can be used for the determination of sex and stature of an individual in forensic investigations. No systematic studies are available on the determination of sex from foot measurements of North Indians. Therefore, foot index is derived to determine the sex of an individual in a single community of North India. The foot index for both genders is derived by dividing the foot breadth by foot length and multiplying it by hundred. In the present investigation, the foot index is found to be slightly higher in females in the right foot and males in the left foot. The study suggests that although foot length and foot breadth show significant sex differences, sex determination cannot be made conclusively from the foot index.