Outcome of Adjuvant Radiotherapy and Adjuvant Chemoradiation for Oral Cancers with Close Margins of Resection.

Oral cancers comprise 50% of all head and neck malignancies in India which can be attributed to tobacco chewing. Advanced oral cancers are managed with surgery followed by adjuvant radiotherapy or adjuvant chemoradiation. There is paucity of studies regarding need for adjuvant treatment in oral cancers with close margins i.e. ≤ 0.5 cm after formalin fixation. This study aims at documenting the oncological outcome with regards to loco-regional control, disease-free survival, overall survival and complications of adjuvant radiotherapy and adjuvant chemoradiation in operated oral cancer patients having close margins of resection. In this Retrospective cohort study, 163 patients with stage T1-T4 oral cancers operated between 2015 and 2019 who have fulfilled the inclusion and exclusion criteria, received adjuvant treatment and could be followed up for at least one year were included. At the end of 45 months, the overall survival was 74.7% and disease specific survival was 82.7%. Among the 7 patients who defaulted radiotherapy, 4 patients succumbed to the disease. Complications were bone marrow depression (2 patients), dysphagia (17) and Trismus (1). Adjuvant radiotherapy should be given in oral cancer patients with close margins of resection since it improves the oncological outcome and disease specific survival and the benefit often outweighs the risk.

A Randomized Controlled Trial on Pranayama and Yoga Nidra for Anxiety and Depression in Patients With Cervical Cancer Undergoing Standard of Care.

Introduction Cervical cancer might intensify the psychological distress among patients with cervical cancer and the distress caused by the diagnosis and treatment. So, depression and anxiety are at higher levels in patients with cervical cancer. Yoga Nidra and Pranayama are thought to reduce the aftereffects of chemotherapy and radiotherapy potentially. So, in this study, we used the techniques of Yoga Nidra and Pranayama to evaluate their effect on patients with cervical cancer undergoing standard care. Methodology Seventy women with cervical cancer were randomized into experimental and control groups. The experimental group of patients with cervical cancer received 30 minutes of yoga intervention twice daily five days a week, for six weeks. The control group was given only the standard of care. The outcome measures were assessed using the Hospital Anxiety and Depression Scale (HADS) questionnaire. The assessment was done at baseline, second, fourth, and sixth weeks. Results The results of within­group comparisons in both groups showed that there was a significant improvement in depression and anxiety scores, with P ≤ 0.05 being considered statistically significant. Between groups, analysis shows that in the preintervention, there was no difference between the yoga and control group as P > 0.05. After the yoga intervention, there was an enhancement in depression and anxiety scores.  Conclusions The results of the study concluded that the Yoga Nidra and Pranayama module can be given as adjuvant therapy to the standard of care in patients with cervical cancer for treating the disease and treatment-related anxiety and depression.

Perception of women on safety and efficacy of contraceptives: A comparative study.

Background: Contraceptive information and services are fundamental to the health and human rights of all individuals. Low contraceptive use is a major challenge faced in India. To determine whether a lack of awareness of contraceptive methods was a factor, we assessed the perception of women on contraceptive methods, their safety and efficacy and further determined whether their demographic background played any role in their perception. Materials and Methods: Reproductive-aged women from both rural and urban backgrounds of Bangalore and Tumkur, Karnataka, were individually questioned in a community setting using both Google Forms and personal interviews from September 2022 to December 2022. The questions consisted of limited demographic information and specific questions related to the knowledge and beliefs of women on the efficacy and safety of contraceptive methods and assessed situational awareness. Results: Although awareness was more amongst urban women (99.1%) compared with rural women (79%), the practice was significantly higher amongst rural women (63.2%) compared with urban women (36.7%). Perception showed variations with respect to age, education, religion and parity. A major religion-wise disparity was observed. With regard to safety, oral contraceptive pills (60.9%) and condoms (51.8%) were unanimously perceived to be the most and least harmful to health. The most commonly perceived short-term complications were found to be body changes, and mood swings, tiredness and infertility with no data to support the claim were the most commonly chosen long-term complication. Conclusion: From the study, we concluded that more educated women were not immune to misinformation. The efficacy rates of different methods were highly underestimated with methods with higher failure rates perceived to be more effective. Results demonstrate that women are ill-informed about the long-term complications of various methods.

Quantifying assays: inhibition of signalling pathways of cancer.

Inhibiting a signalling pathway concerns controlling the cellular processes of a cancer cell's viability, cell division and death. Assay protocols created to see if the molecular structures of the drugs being tested have the desired inhibition qualities often show great variability across experiments, and it is imperative to diminish the effects of such variability while inferences are drawn. In this paper, we propose the study of experimental data through the lenses of a mathematical model depicting the inhibition mechanism and the activation-inhibition dynamics. The method is exemplified through assay data obtained from an experimental study of the inhibition of the chemokine receptor 4 (CXCR4) and chemokine ligand 12 (CXCL12) signalling pathway of melanoma cells. The quantitative analysis is conducted as a two step process: (i) deriving theoretically from the model the cell viability as a function of time depending on several parameters; (ii) estimating the values of the parameters by using the experimental data. The cell viability is obtained as a function of concentration of the inhibitor and time, thus providing a comprehensive characterization of the potential therapeutic effect of the considered inhibitor, e.g. $IC_{50}$ can be computed for any time point.

Calcifying odontogenic cyst associated with compound odontoma - A rare entity.

Calcifying odontogenic cyst (COC) or Gorlin's cyst categorized as a distinct entity by Gorlin et al. in 1962. It is a rare benign developmental cystic lesion that accounts for less than 1% of all odontogenic cysts. It can occur in association with various types of odontogenic tumors such as odontomas. COC is a hybrid lesion of the jaw presenting a manifold variety of clinical behaviors and histopathological characteristics including cystic, solid (neoplastic), and aggressive forms. COC exhibits diversity in terms of its clinical presentations, histopathologic features, and biological behavior. Normally, it presents as asymptomatic, slow developing lesion affecting the maxilla and mandible equally with strong predilection for the anterior segment. Radiographically, these lesions usually present as a unilocular, well-defined radiolucency with radiopaque structures within the lesion, either as irregular calcifications or tooth-like densities. The distinct features of COC as solid or cystic lesions presents with an ameloblastomous component admixed with varying proportions of ghost cells and spherical calcifications. Here, we report an article of calcifying odontogenic cyst associated with compound odontoma in a young patient with lesion in the anterior mandible with review of the various terminologies and classification and histopathology.

ArpC5 isoforms regulate Arp2/3 complex-dependent protrusion through differential Ena/VASP positioning.

Regulation of the Arp2/3 complex is required for productive nucleation of branched actin networks. An emerging aspect of regulation is the incorporation of subunit isoforms into the Arp2/3 complex. Specifically, both ArpC5 subunit isoforms, ArpC5 and ArpC5L, have been reported to fine-tune nucleation activity and branch junction stability. We have combined reverse genetics and cellular structural biology to describe how ArpC5 and ArpC5L differentially affect cell migration. Both define the structural stability of ArpC1 in branch junctions and, in turn, by determining protrusion characteristics, affect protein dynamics and actin network ultrastructure. ArpC5 isoforms also affect the positioning of members of the Ena/Vasodilator-stimulated phosphoprotein (VASP) family of actin filament elongators, which mediate ArpC5 isoform-specific effects on the actin assembly level. Our results suggest that ArpC5 and Ena/VASP proteins are part of a signaling pathway enhancing cell migration.

Deciphering the molecular mechanisms of actin cytoskeleton regulation in cell migration using cryo-EM.

The actin cytoskeleton plays a key role in cell migration and cellular morphodynamics in most eukaryotes. The ability of the actin cytoskeleton to assemble and disassemble in a spatiotemporally controlled manner allows it to form higher-order structures, which can generate forces required for a cell to explore and navigate through its environment. It is regulated not only via a complex synergistic and competitive interplay between actin-binding proteins (ABP), but also by filament biochemistry and filament geometry. The lack of structural insights into how geometry and ABPs regulate the actin cytoskeleton limits our understanding of the molecular mechanisms that define actin cytoskeleton remodeling and, in turn, impact emerging cell migration characteristics. With the advent of cryo-electron microscopy (cryo-EM) and advanced computational methods, it is now possible to define these molecular mechanisms involving actin and its interactors at both atomic and ultra-structural levels in vitro and in cellulo. In this review, we will provide an overview of the available cryo-EM methods, applicable to further our understanding of the actin cytoskeleton, specifically in the context of cell migration. We will discuss how these methods have been employed to elucidate ABP- and geometry-defined regulatory mechanisms in initiating, maintaining, and disassembling cellular actin networks in migratory protrusions.

Outcome of Treatment in Verrucous Carcinoma of Oral Cavity: A Tertiary Rural Hospital Experience.

Verrucous carcinoma of oral cavity is a highly well differentiated variant of squamous cell carcinoma with a low potential for invasion and metastasis. It is prevalent in the tobacco quid chewing population in our region. In this observational study, we reviewed the medical case records of 58 patients treated for oral verrucous carcinoma staged T2 to T4a. All patients underwent wide excision of tumour which included marginal mandibulectomy in 22 and hemimandibulectomy in 23 patients along with neck dissection saving the accessory nerve and internal jugular vein. 5 patients were found to have bone involvement along the alveolar sockets. 11 patients had other associated premalignant lesions in oral cavity. Only 2 patients had lymph node metastasis without extra nodal spread in submandibular region. With a mean follow up of 6 years and minimum follow up of 1 year, 3 patients had local recurrence. All these 3 patients had bone involvement and 2 of them had lymph node metastasis on histopathological examination. 3 patients who had associated premalignant lesions developed second primary in oral cavity after 3 years. In our experience, verrucous carcinoma has good prognosis when treated by surgery. Bone involvement along alveolar sockets and associated oral premalignant lesions adversely affect the outcome. There was no difference in the outcome between selective and modified radical neck dissection. Therefore selective neck dissection (supraomohyoid) would be adequate in treating these patients. Adjuvant radiotherapy can be reserved for T4a lesions or for positive margins.

Piperine, an active ingredient of white pepper, suppresses the growth of multidrug-resistant toxigenic Vibrio cholerae and other pathogenic bacteria.

Emergence and rapid spread of multidrug-resistant (MDR) bacteria including Vibrio cholerae are a global public health issue. Much attention has been paid to natural compounds, such as spices and herbs to find novel antimicrobial compounds as they are considered to be cheaper alternatives to develop as a drug. Here, we show that methanol extract of white pepper could inhibit the growth of V. cholerae O1 El Tor variant, responsible for the recent outbreaks/epidemics. Furthermore, we demonstrate for the first time that piperine, the major component of white pepper, showed a dose-dependent bactericidal effect on V. cholerae growth irrespective of their biotypes and serogroups in the presence of 200 and 300 µg ml-1 of piperine, respectively. Piperine also inhibited the growth of MDR strains of Pseudomonas aeruginosa, Escherichia coli isolated from poultry and enterohemorrhagic/enteroaggregative E. coli O104 in the presence of 200 µg ml-1 . Interestingly, we did not observe any significant inhibitory effect of piperine on E. coli strains isolated from healthy person even up to 200 µg ml-1 . Our data suggest that piperine could be a novel antimicrobial agent in therapeutic and preventive applications against infections caused by pathogenic bacteria including MDR strains.

An Echo State Network Imparts a Curve Fitting.

Recurrent neural networks (RNNs) are successfully employed in processing information from temporal data. Approaches to training such networks are varied and reservoir computing-based attainments, such as the echo state network (ESN), provide great ease in training. Akin to many machine learning algorithms rendering an interpolation function or fitting a curve, we observe that a driven system, such as an RNN, renders a continuous curve fitting if and only if it satisfies the echo state property. The domain of the learned curve is an abstract space of the left-infinite sequence of inputs and the codomain is the space of readout values. When the input originates from discrete-time dynamical systems, we find theoretical conditions under which a topological conjugacy between the input and reservoir dynamics can exist and present some numerical results relating the linearity in the reservoir to the forecasting abilities of the ESNs.

Primary cutaneous amyloidosis: A clinicopathological, histochemical, and immunohistochemical study.

BACKGROUND: Primary cutaneous amyloidosis (PCA) comprises several forms of localized cutaneous amyloidosis characterized by amyloid deposits occurring at or near dermal-epidermal junctions. Immunohistochemical studies have shown the expression of cytokeratin (CK) suggesting that it has an epidermal origin. OBJECTIVES: To study the clinicopathological features of PCA and expression of CK5/6 and correlate it with Congo red stain. MATERIALS AND METHODS: A total of 30 histologically proven cases of PCA were studied. Congo red staining and immunohistochemical expression of CK5/6 were analyzed. STATISTICAL ANALYSIS: : The qualitative data has been expressed as proportions and the quantitative data has been expressed as mean ± SD. All data was analyzed using the Statistical Package for Social Sciences (SPSS) software version 22. RESULTS: Deposits of amyloid in papillary dermis were seen in all 30 cases. Mild focal basal cell vacuolar degeneration and apoptotic bodies in epidermis were seen in six cases. The presence of pigment cells in dermis were seen in 26 cases. CK5/6 showed weak/mild immunopositivity in nine cases, moderate in 20 cases, and strong in one case. CONCLUSION: The presence of dermal melanophages interspersed within eosinophilic deposits gives a clue to the diagnosis. Congo red stain highlights the deposits and visualization under polarized light gives apple green birefringence which is diagnostic of amyloid. Staining of amyloid deposits by CK5/6 proves that the amyloid is of keratinocyte origin. There was 100% sensitivity with Congo red and CK5/6. Thus, CK5/6 can be used as an adjunct tool to Congo red stain in the diagnosis of primary cutaneous amyloidosis.

Structural insights into actin filament recognition by commonly used cellular actin markers.

Cellular studies of filamentous actin (F-actin) processes commonly utilize fluorescent versions of toxins, peptides, and proteins that bind actin. While the choice of these markers has been largely based on availability and ease, there is a severe dearth of structural data for an informed judgment in employing suitable F-actin markers for a particular requirement. Here, we describe the electron cryomicroscopy structures of phalloidin, lifeAct, and utrophin bound to F-actin, providing a comprehensive high-resolution structural comparison of widely used actin markers and their influence towards F-actin. Our results show that phalloidin binding does not induce specific conformational change and lifeAct specifically recognizes closed D-loop conformation, i.e., ADP-Pi or ADP states of F-actin. The structural models aided designing of minimal utrophin and a shorter lifeAct, which can be utilized as F-actin marker. Together, our study provides a structural perspective, where the binding sites of utrophin and lifeAct overlap with majority of actin-binding proteins and thus offering an invaluable resource for researchers in choosing appropriate actin markers and generating new marker variants.

Synthesis of 6-[4-(4-Propoxyphenyl)piperazin-1-yl]-9H-purine Derivatives as Antimycobacterial and Antifungal Agents: In Vitro Evaluation and In Silico Study.

A series of novel alkyl substituted purines were synthesized. 6-[4-(4-Propoxyphenyl)piperazin-1-yl]-9H-purine was used as the key starting material, which was synthesized via a multistep protocol and finally subjected for N-alkylation with various alkyl halides with an aim to get prospective antimicrobial agents. The structures of the novel compounds were established by substantiating them through spectral techniques like 1 H-NMR, 13 C-NMR, FT-IR and EI-MS. They were explored for antitubercular activity against Mycobacterium tuberculosis H37RV. Furthermore, they were checked for their antimicrobial activity concerning bacterial and fungal strains. The title compounds exhibited considerable antimicrobial activity without any significant toxicity. In silico studies depicted their good binding profile against Mycobacterium tuberculosis enoyl reductase (InhA; PDB ID: 4TZK) and Candida albicans dihydrofolate reductase (PDB ID: 1AI9). The title compounds obeyed Lipinski's parameters and have exhibited good drug-like properties.

The Spectrum of Congenital Central Nervous System Anomalies Among Stillborn: An Autopsy Based Study.

BACKGROUND: Congenital central nervous system (CNS) anomalies are the structural or functional abnormalities of the brain and spinal cord that occur during the intrauterine developmental process. PURPOSE: The present study aims to detect the prevalence of congenital CNS anomalies among stillborn fetuses, the association between congenital anomalies and maternal factors, and also the association between autopsy and ultrasound findings. METHODS: This study was conducted on 50 stillborn fetuses, obtained from the Department of Obstetrics and Gynecology at JSS Medical College and Hospital, Mysuru. The fetuses were fixed in 10% formalin and autopsies were performed as per the standard fetal autopsy protocol. The congenital CNS anomalies were studied in detail. RESULTS: CNS anomalies were the most common congenital anomalies observed. Out of the total 50 stillborn fetuses studied, CNS anomalies were found in 17 fetuses and their occurrence was more common among male stillborn than females. Meningomyelocele was the most common anomaly, followed by anencephaly. The other anomalies documented were meningocele, encephalocele, meningoencephalocele, agenesis of the corpus callosum, craniorachischisis, bifid cerebellum with hypoplastic vermis, holoprosencephaly, and sirenomelia.Fisher's exact test showed a significant association between maternal hypothyroidism and congenital CNS anomalies (P < .05). The autopsy confirmed the ultrasound findings in 40 (80%) fetuses. There were significant additional findings observed in seven (14%) fetal autopsies and ultrasound diagnosis completely changed in three (6%) cases, after the final autopsy procedure. CONCLUSION: The fetal autopsy is the single most directly evident investigation, which gives information that changes or significantly improves the clinical diagnosis. A multidisciplinary holistic approach toward pregnancy will help to detect any kind of abnormality in the fetus and thus to take a timely decision toward the management.

Bacterial chromosome organization. I. Crucial role of release of topological constraints and molecular crowders.

We showed in our previous studies that just 3% cross-links (CLs), at special points along the contour of the bacterial DNA, help the DNA-polymer to get organized at micron length scales [T. Agarwal et al., J. Phys.: Condens. Matter 30, 034003 (2018) and T. Agarwal et al., EPL (Europhys. Lett.) 121, 18004 (2018)]. In this work, we investigate how does the release of topological constraints help in the "organization" of the DNA-polymer. Furthermore, we show that the chain compaction induced by the crowded environment in the bacterial cytoplasm contributes to the organization of the DNA-polymer. We model the DNA chain as a flexible bead-spring ring polymer, where each bead represents 1000 base pairs. The specific positions of the CLs have been taken from the experimental contact maps of the bacteria Caulobacter crescentus and Escherichia coli. We introduce different extents of ease of release of topological constraints in our model by systematically changing the diameter of the monomer bead. It varies from the value where chain crossing can occur freely to the value where chain crossing is disallowed. We also study the role of compaction of the chain due to molecular crowders by introducing an "effective" weak Lennard-Jones attraction between the monomers. Using Monte Carlo simulations, we show that the release of topological constraints and the crowding environment play a crucial role to obtain a unique organization of the polymer.

Bacterial chromosome organization. II. Few special cross-links, cell confinement, and molecular crowders play the pivotal roles.

Using a coarse-grained bead-spring model of bacterial chromosomes of Caulobacter crescentus and Escherichia coli, we show that just 33 and 38 effective cross-links in 4017 and 4642 monomer chains at special positions along the chain contour can lead to the large-scale organization of the DNA polymer, where confinement effects of the cell walls play a key role in the organization. The positions of the 33/38 cross-links along the chain contour are chosen from the Hi-C contact map of bacteria C. crescentus and E. coli. We represent 1000 base pairs as a coarse-grained monomer in our bead-spring flexible ring polymer model of the DNA polymer. Thus, 4017/4642 beads on a flexible ring polymer represent the C. crescentus/E. coli DNA polymer with 4017/4642 kilo-base pairs. Choosing suitable parameters from Paper I, we also incorporate the role of compaction of the polymer coil due to the presence of molecular crowders and the ability of the chain to release topological constraints. We validate our prediction of the organization of the bacterial chromosomes with available experimental data and also give a prediction of the approximate positions of different segments within the cell. In the absence of confinement, the minimal number of effective cross-links required to organize the DNA chains of 4017/4642 monomers was 60/82 [Agarwal et al., Europhys. Lett. 121, 18004 (2018) and Agarwal et al., J. Phys.: Condens. Matter 30, 034003 (2018)].

Detection of cancer stem cell-related markers in different stages of colorectal carcinoma patients of Indian origin by immunohistochemistry.

CONTEXT: Although the incidence rate of colorectal cancer (CRC) in all Indian cancer registries is very close to the lowest rate in the world, westernization has shown an increasing trend in the recent years. Recurrence is reported in CRC because the slowly proliferating stem cells escape the chemotherapeutic regimen. AIM: To detect the presence of CD133 and CD44 in human CRC specimens and to correlate the level of marker expression with tumor staging. MATERIALS AND METHODS: We included 26 colorectal carcinoma patients between 20 and 70 years of age. Histological and immunohistochemical analysis of CD133 and CD44 was done in sections of 5 µm prepared from paraffin-embedded blocks with most representative areas. STATISTICAL ANALYSIS: All analyses were performed using Microsoft Excel 2010 and SPSS version 22. RESULTS: CD133 expression was seen exclusively on the cell membrane at the glandular luminal surface with dot-like cytoplasmic staining. In the normal mucosa, CD44 expression was seen in the superficial region of the cell, whereas in most of the carcinomas, the staining was localized in the basolateral region of the cell. Both CD133 and CD44 showed significant correlation with tumor stage. CONCLUSIONS: In the present study, CD133 and CD44 show significant correlation with tumor staging. Cancer stem cell markers have shown similar pattern of expression in the patients of Indian origin. Using combination of markers for staging is preferred as it increases the sensitivity and specificity.

Outcome of compartment resection of locally advanced oral cancers extending to infratemporal fossa: a tertiary rural hospital experience.

Locally advanced oral cancers extending to infratemporal fossa (ITF) are a challenge to head and neck surgeons. These tumors are classified as T4b whenever the masticator space (MS), pterygoid muscles (PM), and pterygoid plates (PP) are involved according to AJCC classification. Until recently, these tumors were considered inoperable and treated only with palliative intent. However, a few studies in the last decade showed that many of these tumors could be resected with a reasonably favorable prognosis by compartment resection of ITF, particularly when the tumor was below sigmoid notch of mandible. A few studies attempted to downstage these tumors by neo-adjuvant chemotherapy before attempting resection. Oral Squamous cell carcinoma has a high prevalence in South India. Majority of these patients are females addicted to tobacco quid chewing and present with locally advanced disease. In this retrospective analysis, we evaluated the outcome of treatment of oral squamous cell carcinoma extending to ITF and staged T4b in 52 patients. All patients underwent Composite resection including compartment resection of ITF followed by adjuvant treatment. 20 patients had received neo-adjuvant chemotherapy. Pectoralis major myocutaneous flap was the mainstay of reconstruction. After mean follow-up of 2 years, 31 patients are alive and disease free. 14 patients had local recurrence in ITF and 2 patients had recurred in cervical nodes. 8 patients died due to disease and 6 are on palliative care. Neo-adjuvant chemotherapy did not benefit the outcome. Close margins of resection, extra nodal spread from lymph nodes and supra notch and involvement of posterior part of ITF were factors which predisposed to recurrence.

Structure function relations in PDZ-domain-containing proteins: Implications for protein networks in cellular signalling.

Protein scaffolds as essential backbones for organization of supramolecular signalling complexes are a recurrent theme in several model systems. Scaffold proteins preferentially employ linear peptide binding motifs for recruiting their interaction partners. PDZ domains are one of the more commonly encountered peptide binding domains in several proteins including those involved in scaffolding functions. This domain is known for its promiscuity both in terms of ligand selection, mode of interaction with its ligands as well as its association with other protein interaction domains. PDZ domains are subject to several means of regulations by virtue of their functional diversity. Additionally, the PDZ domains are refractive to the effect of mutations and maintain their three-dimensional architecture under extreme mutational load. The biochemical and biophysical basis for this selectivity as well as promiscuity has been investigated and reviewed extensively. The present review focuses on the plasticity inherent in PDZ domains and its implications for modular organization as well as evolution of cellular signalling pathways in higher eukaryotes.