Impact of ABCB1 and ABCG2 Transporter in Outcome of Gallbladder Cancer.

Background: Gallbladder cancer (GBC) is a biologically aggressive malignancy requiring appropriate biomarkers to improve its outcome. Role of ABC transporters (ABCB1 and ABCG2) has been linked to cancer aggressiveness, tumorigenesis and multidrug resistance. Herein, we studied the prognostic implication of ABCB1 and ABCG2 in GBC. Methods: Fresh tissue (tumour & normal) samples collected from 54 patients who underwent R0 resection, were analysed for mRNA and protein expression of ABCB1 and ABCG2 by quantitative Real-Time PCR and western blotting, respectively, in this prospective study. The molecular findings were correlated with clinical-pathological parameters using χ2 and fisher exact test. The molecular changes in ABCB1 and ABCG2 were analysed for predicting overall survival (OS), disease-free survival (DFS) and response to chemotherapy using Kaplan-Meier log-rank test and Cox regression multivariate analysis. Results: The mean age of the cohort was 50 ± 13.2 with 26 (48.1%) in patients having early stage gallbladder cancer (GBC). Over-expression of ABCB1 and ABCG2 was noted in 32/54 (59%) and 40/54 (74%) cases, respectively. The protein expression of ABCB1(P-glycoprotein) and ABCG2 (BCRP) was higher in 27/54 (50%) and 37/54 (59%) cases, respectively. The mean OS and DFS was 20.7 ± 11.5 and 19.3 ± 12.2 months at median follow-up of 24 months. The TNM stage, lymph node metastasis, and presence of gallstone were significant factors for predicting OS and DFS on multivariate analysis. Both ABCB1 and ABCG2 did not show any significant correlation with OS and DFS with similar incidences of late death and recurrence among over-expression and down-expression. Sub-group comparison suggests that change in expression pattern of ABCB1 and ABCG2 may not affect response to chemotherapy in GBC. Conclusion: Altered expression of ABCB1 and ABCG2 may not be a useful prognostic marker for survival or response to chemotherapy in GBC. Presently, histo-pathological characteristics and associated gallstones are the important predictors for survival and recurrence in GBC.

Harnessing nature's potential: Alpinia galanga methanolic extract mediated green synthesis of silver nanoparticle, characterization and evaluation of anti-neoplastic activity.

With the advent of nanotechnology, the treatment of cancer is changing from a conventional to a nanoparticle-based approach. Thus, developing nanoparticles to treat cancer is an area of immense importance. We prepared silver nanoparticles (AgNPs) from methanolic extract of Alpinia galanga rhizome and characterized them by UV-Vis spectrophotometry, Fourier transform Infrared (FTIR) spectroscopy, Zetasizer, and Transmission electron Microscopy (TEM). UV-Vis spectrophotometry absorption spectrum showed surface plasmon between 400 and 480 nm. FTIR spectrum analysis implies that various phytochemicals/secondary metabolites are involved in the reduction, caping, and stabilization of AgNPs. The Zetasier result suggests that the particles formed are small in size with a low polydispersity index (PDI), suggesting a narrow range of particle distribution. The TEM image suggests that the particles formed are mostly of spherical morphology with nearly 20-25 nm. Further, the selected area electron diffraction (SAED) image showed five electron diffraction rings, suggesting the polycrystalline nature of the particles. The nanoparticles showed high anticancer efficacy against cervical cancer (SiHa) cell lines. The nanostructures showed dose-dependent inhibition with 40% killing observed at 6.25 µg/mL dose. The study showed an eco-friendly and cost-effective approach to the synthesis of AgNPs and provided insight into the development of antioxidant and anticancer agents.

Advanced Analysis of the Properties of Solid-Wire Electric Contacts Produced by Ultrasonic Welding and Soldering.

The current article presents an advanced analysis of the properties of solid-wire electric contacts produced with ultrasonic welding and soldering. Soldering is generally used to join thin, solid copper wires to produce electrical contacts in small-volume production, as ultrasonic welding does not provide acceptable peel force and tensile strength due to the deformation and thinning of the wires. In this article, ultrasonic welding of thin, solid copper wires using a ring before and after a thermal shock test is discussed and compared with the standard soldering technique. The thermal shock test was carried out in the temperature range from -30 to 150 °C. Half of the samples, for both the joining techniques and the wires, were subjected to the thermal shock test; the other half were not. Investigations included electrical resistance tests, optical and SEM microscopy, XRD, microhardness measurements, peel tests, tensile tests, and fractographic analysis. The electrical resistance test, microscopy, microhardness measurements, and fracture examinations showed no differences between the thermal shock-exposed and the non-exposed samples with the same joining process. In mechanical tests, the ultrasonic joint demonstrated superior strength compared to the soldered joint.

Palate shape is associated with Unilateral Hypoglossal Nerve Stimulation Outcomes.

OBJECTIVE: The aim was to determine the potential association between palate shape and unilateral hypoglossal nerve stimulation (HNS) outcomes. METHODS: Preoperative drug-induced sleep endoscopy (DISE) videos were reviewed and scored by 3 blinded reviewers to determine airway narrowing at the hard-soft palate junction (HP), soft palate genu, and inferior velum, as described by Woodson (2014). Scoring was as follows: 1-open airway, 2-narrow, 3-severe narrowing. Overall palate shape (oblique, intermediate, or vertical) was determined based on prior criteria. Successful surgical treatment was defined by the HNS titration polysomnogram as a reduction of ≥50% in the apnea-hypopnea index (AHI) to <15 events/h. RESULTS: Of 332 adults, the majority was male (77%) with an average BMI of 29.2 ± 3.6 kg/m2 . Overall success rate was 73%. Success rate was lower in patients with vertical palate shape compared with the other shapes (56% vs. 75%, p = 0.029). HP score 3 compared with scores 2 and 1 was associated with lower success rates (60% vs. 76%, p = 0.028), but genu and velum scores were not associated with outcomes. Patients with both HP score 3 and complete oropharyngeal lateral wall-related obstruction had notably worse outcomes (22% vs. 74%, p = 0.026). HP score 3 (OR 0.45, 95%CI 0.22-0.92) and vertical palate shape (OR 0.33, 95%CI 0.15-0.78) were independently associated with lower odds of surgical response after adjustment for DISE findings, age, gender, and BMI. CONCLUSION: Vertical palate shape and narrowing at the hard-soft palate junction are independently associated with lower HNS surgical success rates. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:981-986, 2024.

Development and Evaluation of Solid Dispersion-Based Sublingual Films of Nisoldipine.

Nisoldipine (NIS) is a calcium channel blocker that exhibits poor bioavailability (~5%) due to low aqueous solubility and presystemic metabolism in the gut wall. In this context, the present work aimed to develop NIS solid dispersion (NISSD)-based sublingual films using solvent casting technique to improve the dissolution. Phase solubility studies indicated that Soluplus® was the most effective carrier for improving the aqueous solubility of NIS. NISSDs were initially developed using the solvent evaporation method. Fourier transform infrared spectrometric studies were found to display the characteristic vibrational bands related to C=O stretching and N-H deformation in NISSDs, proving the chemical integrity of the drug in NISSDs. Subsequently, bioadhesive sublingual films of NISSDs were formulated using solvent casting method, using hydroxypropyl methyl cellulose (HPMC) E5, E15, and hydroxy ethyl cellulose (HEC EF) as hydrophilic polymers and polyethylene glycol 400 (PEG 400) as plasticizer. The incorporation of NISSDs was found to produce clear films that displayed uniform content. The sublingual film of NISSDs composed of HPMC E5 (2% w/v), was found to display the least thickness (0.29 ± 0.02 mm), the highest folding endurance (168.66 ± 4.50 times), and good bioadhesion strength (12.73 ± 0.503 g/cm2). This film was found to rapidly disintegrate (28.66 ± 3.05 sec) and display near-complete drug release (94.24 ± 1.22) in 30 min. Incorporating NISSDs into rapidly bioadhesive sublingual films considerably improves drug dissolution. Overall, these research outcomes underscored the potential of rapidly dissolving bioadhesive sublingual films to evade gut metabolism and resolve the bioavailability issues associated with oral administration of NIS.

A Review on Multiplicity in Multi-Material Additive Manufacturing: Process, Capability, Scale, and Structure.

Additive manufacturing (AM) has experienced exponential growth over the past two decades and now stands on the cusp of a transformative paradigm shift into the realm of multi-functional component manufacturing, known as multi-material AM (MMAM). While progress in MMAM has been more gradual compared to single-material AM, significant strides have been made in exploring the scientific and technological possibilities of this emerging field. Researchers have conducted feasibility studies and investigated various processes for multi-material deposition, encompassing polymeric, metallic, and bio-materials. To facilitate further advancements, this review paper addresses the pressing need for a consolidated document on MMAM that can serve as a comprehensive guide to the state of the art. Previous reviews have tended to focus on specific processes or materials, overlooking the overall picture of MMAM. Thus, this pioneering review endeavors to synthesize the collective knowledge and provide a holistic understanding of the multiplicity of materials and multiscale processes employed in MMAM. The review commences with an analysis of the implications of multiplicity, delving into its advantages, applications, challenges, and issues. Subsequently, it offers a detailed examination of MMAM with respect to processes, materials, capabilities, scales, and structural aspects. Seven standard AM processes and hybrid AM processes are thoroughly scrutinized in the context of their adaptation for MMAM, accompanied by specific examples, merits, and demerits. The scope of the review encompasses material combinations in polymers, composites, metals-ceramics, metal alloys, and biomaterials. Furthermore, it explores MMAM's capabilities in fabricating bi-metallic structures and functionally/compositionally graded materials, providing insights into various scale and structural aspects. The review culminates by outlining future research directions in MMAM and offering an overall outlook on the vast potential of multiplicity in this field. By presenting a comprehensive and integrated perspective, this paper aims to catalyze further breakthroughs in MMAM, thus propelling the next generation of multi-functional component manufacturing to new heights by capitalizing on the unprecedented possibilities of MMAM.

Clinical significance of SPOP and APC gene alterations in colorectal cancer in Indian population.

Speckle-Type Poz Protein (SPOP) involved in the regulation of proteasome-mediated degradation of several oncoproteins, resulting in cancer initiation and progression. Mutations in Adenomatous Polyposis Coli (APC) gene is reported in most sporadic and hereditary colorectal cancer (CRC). Identifying the cellular changes involved in carcinogenesis when APC is mutated is an important issue that needs attention. The tumor suppressive function of SPOP and APC has long been a major focus in the research field of colorectal cancer. However, the clinical significance of SPOP and APC gene alteration in CRC has not been established to date. Mutational analysis was performed by single-strand conformational polymorphism followed by Sanger sequencing, methylation status by methylation-specific PCR, and protein expression by immunohistochemistry on 142 tumor tissues along with their adjacent non-cancerous specimens. The overall survival (OS) and recurrence free survival (RFS) were estimated by Kaplan-Meier Curve. Mutation rates of APC and SPOP gene were 2.8% and 11.9% while that of promoter hypermethylation were 37% and 47%, respectively. The grade of differentiation and Lymph node metastasis were significantly correlated with APC methylation pattern (p ≤ 0.05). The down regulation of APC was more often seen in colonic cancer compared to rectal cancer (p = 0.07) and more commonly in T3-4 depth of invasion (p = 0.07) and in patients without lymphovascular and perineural invasion (p = 0.007, p = 0.08 respectively). The median overall survival and recurrence free survival (RFS) was 67 & 36 months while 3-yr and 5-yr OS and RFS were 61.1% & 56.4% and 49.2% & 44.8%, respectively. APC promoter methylation had a better overall survival (p = 0.035) while loss of SPOP expression had a worse survival (p = 0.09). Our findings reveal high percentage of SPOP gene mutations in CRC. A significant link is found between promoter hyper methylation and protein expression in all mutant cases of APC and SPOP, suggesting that both genes may be associated in the development of colorectal cancer in people of Indian decent. Hypermethylation of APC gene and loss of SPOP expression have shown an association with disease prognosis and could be further studied looking at its potential role in planning adjuvant treatment in CRC patients.

Clinical utility of smartphone applications for sleep physicians.

PURPOSE: To review various smartphone applications (apps) for sleep architecture and screening of obstructive sleep apnea (OSA) and to outline their utility for sleep physicians. METHODS: Mobile application stores (Google Play and Apple iOS App Store) were searched for sleep analysis applications (apps) that are targeted for consumer use. Apps were identified by two independent investigators for apps published through July 2022. App information including parameters obtained for sleep analysis were extracted from each app. RESULTS: The search identified 50 apps that reported sufficient outcome measures to be considered for assessment. Half of the apps tracked sleep with phone-only technology, while 19 utilized sleep and fitness trackers, three utilized sleep-only wearable devices, and three utilized nearable devices. Seven apps provided data useful for tracking users for signs and symptoms of obstructive sleep apnea. CONCLUSION: There are a variety of sleep analysis apps available on the market to consumers currently. Though the sleep analysis of these apps may not be validated, sleep physicians should be aware of these apps to improve understanding and education of their patients.

The Mucosal Manifestations of Syphilis in the Head and Neck.

Objectives: Syphilis is a resurging disease which can present itself in many ways, including lesions within the head and neck mucosa. Some of these lesions may clinically mimic oral malignancies. This literature review aims to better characterize the mucosal presentations of syphilis. Methods: PubMed, EMBASE, and clinicaltrials.gov were searched for full-text, English articles published from 1950 to 2022 that reported patients with head and neck mucosal manifestations of syphilis. Articles were screened according to PRISMA guidelines. Results: One hundred forty-three manuscripts documenting 236 individual patients were included in the review. Patients with secondary syphilis accounted for 62% of patients presenting with head and neck mucosal lesions. The most common lesions found in primary and secondary syphilis were ulcerations, primarily found on the tongue, lips, and palate. While serologic studies are the gold standard for diagnosing syphilis, biopsy of these lesions have characteristic syphilitic changes. Conclusions: Syphilis' nickname of "The great imitator" remains to be true, and the head and neck mucosal manifestations of this disease can resemble commonly seen malignancies. Awareness of this disease and its lesions is prudent given the rising incidence of syphilis within the United States.

Mannose-binding lectin gene 2 variant DD (rs 5030737) is associated with susceptibility to COVID-19 infection in the urban population of Patna City (India).

The study aimed to measure plasma levels of Mannose-Binding Lectin (MBL) and MBL-associated serine protease-2 (MASP-2) and their polymorphisms in COVID-19 patients and controls to detect association. As MBL is a protein of immunological importance, it may contribute to the first-line host defence against SARS-CoV-2. MBL initiates the lectin pathway of complement activation with help of MASP-1 and MASP-2. Hence, appropriate serum levels of MBL and MASPs are crucial in getting protection from the disease. The polymorphisms of MBL and MASP genes affect their plasma levels, impacting their protective function and thus may manifest susceptibility, extreme variability in the clinical symptoms and progression of COVID-19 disease. The present study was conducted to find plasma levels and genetic variations in MBL and MASP-2 in COVID-19 patients and controls using PCR-RFLP and ELISA, respectively.The present study was conducted to find plasma levels and genetic variations in MBL and MASP-2 in COVID-19 patients and controls using PCR-RFLP and ELISA, respectively. Our results indicate that median serum levels of MBL and MASP-2 were significantly low in diseased cases but attained normal levels on recovery. Only genotype DD was found to be associated with COVID-19 cases in the urban population of Patna city.

Phenotypic cross-species conservation and cross-generation directionality switching in epigenetic inheritance.

Evidence supporting non-DNA sequence-based inheritance in animals has increasingly been described in recent years, often under intergenerational inheritance or transgenerational epigenetic inheritance (TEI). Existence of the latter, a stronger indicator of germline transmission, has been demonstrated in invertebrates and mammals alike. The mechanisms and physiological implications of TEI, however, remain unclear. Here, in an unbiased approach, we compared existing transcriptomic data associated with so far available Drosophila models of inter- and trans-, and rodent models of inter-generational inheritance; observed phenotypic cross-species conservation and cross-generation directionality shift therein; and confirmed these observations experimentally in flies. Specifically, previous models of cold and diet-induced inheritance in both flies and mice were commonly associated with altered regulation of proteolysis genes. Besides, fly TEI models were in general characterized by opposite phenotypic regulation in transgenerational offsprings, compared to the ancestors. As insulin-producing cell (IPC) ablation was also associated with proteolysis gene dysregulation in one of the mouse models, we opted to use genetic ablation of IPCs in flies for the experimental validation. Remarkably, the ablation led to transcriptomic alterations across multiple generations, with dysregulated genes showing proteolysis enrichment. Similarly, phenotypic directionality changed in the opposite direction in transgenerational offsprings, in comparison of the ancestors. These results support evolutionary conservation, and both physiologically adaptive and maladaptive consequences of germline mediated epigenetic inheritance.

Machining Strategy Determination for Single- and Multi-Material Wire and Arc Additive Manufactured Thin-Walled Parts.

Wire and arc additive manufacturing (WAAM) technology has recently become attractive due to the fact of its high production capacity and flexible deposition strategy. One of the most prominent drawbacks of WAAM is surface irregularity. Therefore, WAAMed parts cannot be used as built; they require secondary machining operations. However, performing such operations is challenging due to the fact of high waviness. Selecting an appropriate cutting strategy is also challenging, because surface irregularity makes cutting forces unstable. The present research determines the most suitable machining strategy by assessing the specific cutting energy and local machined volume. Up- and down-milling are evaluated by calculating the removed volume and specific cutting energy for creep-resistant steel, stainless steel, and their combination. It is shown that the main factors that affect the machinability of WAAMed parts are the machined volume and specific cutting energy rather than the axial and radial depths of the cut due to the fact of high surface irregularity. Even though the results were unstable, a surface roughness of 0.1 µm was obtained with up-milling. Despite a two-fold difference in the hardness between the two materials in the multi-material deposition, it is found that hardness should not be used as a criterion for as-built surface processing. In addition, the results show no machinability difference between multi- and single-material components for a low machined volume and low surface irregularity.

Anatomical determinants of upper airway collapsibility in obstructive sleep apnea: A systematic review and meta-analysis.

Upper airway (UA) collapsibility is one of the key factors that determine the severity of obstructive sleep apnea (OSA). Interventions for OSA are aimed at reducing UA collapsibility, but selecting the optimal alternative intervention for patients who fail CPAP is challenging because currently no validated method predicts how anatomical changes affect UA collapsibility. The gold standard objective measure of UA collapsibility is the pharyngeal critical pressure (Pcrit). A systematic literature review and meta-analysis were performed to identify the anatomical factors with the strongest correlation with Pcrit. A search using the PRISMA methodology was performed on PubMed for English language scientific papers that correlated Pcrit to anatomic variables and OSA severity as measured by the apnea-hypopnea index (AHI). A total of 29 papers that matched eligibility criteria were included in the quantitative synthesis. The meta-analysis suggested that AHI has only a moderate correlation with Pcrit (estimated Pearson correlation coefficient r = 0.46). The meta-analysis identified four key anatomical variables associated with UA collapsibility, namely hyoid position (r = 0.53), tongue volume (r = 0.51), pharyngeal length (r = 0.50), and waist circumference (r = 0.49). In the future, biomechanical models that quantify the relative importance of these anatomical factors in determining UA collapsibility may help identify the optimal intervention for each patient. Many anatomical and structural factors such as airspace cross-sectional areas, epiglottic collapse, and palatal prolapse have inadequate data and require further research.

Molecular aspects of ABCB1 and ABCG2 in Gallbladder cancer and its clinical relevance.

The function of ABC transporters in the body is manifold; such as maintenance of homeostasis, effect on multi-drug resistance and their role in tumor initiation & progression. Evidence pointing towards the direct or indirect role of ABC transporter genes in particular; ABCB1 and ABCG2 in cancer genesis is increasing. However, their role in gallbladder cancer is unexplored. Therefore, we investigated the methylation status and expression pattern of ABCB1 and ABCG2in gallbladder carcinogenesis. The methylation and expression study of ABCB1/MDR1 and ABCG2/BCRP was performed in tumour and normal fresh tissue samples collected from 61 histopathologically diagnosed gallbladder cancer patients. The methylation status was analysed by Methylation-Specific PCR and expression was determined by Real-Time PCR and Immunohistochemistry. Hypomethylation of ABCB1 and ABCG2 was found in 44 (72.13%) and 48 (78.6%) cases, respectively. ABCB1 hypomethylation pattern showed association with female patients (p = 0.040) and GradeII tumors (p = 0.036) while, ABCG2 hypomethylation was more frequent in early tumors (T1-T2). The mRNA expression ofABCB1 and ABCG2 was up-regulated in 33 (54.10%) and 41 (67.21%) patients with fold change of 4.7 and 5.5, respectively. The mRNA expression of both genes showed association with Grade II tumours and the increased fold change of ABCG2 was higher in (T1-T2) depth of invasion (p = 0.02) and Stage I-II disease (p = 0.08). The protein expression on IHC was strongly positive for ABCB1/MDR1and ABCG2/BCRP in 32 (52.46%) and 45 (73.77%) patients, respectively. The protein expression in ABCG2 showed association with patients age > 50 years (p = 0.04) and GradeII differentiation (p = 0.07). Interestingly, the hypomethylation of both the genes showed significant correlation with increased expression. ABCB1/MDR1 and ABCG2/BCRP hypomethylation and overexpression could have a potential role in gallbladder cancer tumorigenesis especially in early stages. The epigenetic change might be a plausible factor for altered gene expression of ABCB1 and ABCG2 in gallbladder cancer.

How do i salvage that flap?; An evidence-based primer on salvage techniques for head & neck microvascular free flaps.

Interventional strategies for dealing with microvascular free flap failure are varied among institutions and even individual surgeons. This systematic review aims to identify the published methods for salvaging a failing free flap and provide surgeons with a comprehensive toolset for successful intervention. A title and abstract search of the PubMed, Embase, and Web of Science databases was performed. 1694 abstracts were screened by three reviewers according to Prisma guidelines. 62 full text articles meeting inclusion criteria detailed techniques which were separated into the categories of thrombectomy, thrombolysis, leech therapy, vascular fistula, and an "other" category outlining techniques which did not fit into the prior framework. Assessment of the efficacy of individual salvage techniques is limited due to limited empirical data, however, the approach to successful salvage should be based on timely identification of flap compromise, followed by the implementation of one or several of the aforementioned techniques.

Implication of gut microbes and its metabolites in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer with a significant impact on loss of life. In 2020, nearly 1.9 million new cases and over 9,35,000 deaths were reported. Numerous microbes that are abundant in the human gut benefit host physiology in many ways. Although the underlying mechanism is still unknown, their association appears to be crucial in the beginning and progression of CRC. Diet has a significant impact on the microbial composition and may increase the chance of getting CRC. Increasing evidence points to the gut microbiota as the primary initiator of colonic inflammation, which is connected to the development of colonic tumors. However, it is unclear how the microbiota contributes to the development of CRCs. Patients with CRC have been found to have dysbiosis of the gut microbiota, which can be identified by a decline in commensal bacterial species, such as those that produce butyrate, and a concurrent increase in harmful bacterial populations, such as opportunistic pathogens that produce pro-inflammatory cytokines. We believe that using probiotics or altering the gut microbiota will likely be effective tools in the fight against CRC treatment. PURPOSE: In this review, we revisited the association between gut microbiota and colorectal cancer whether cause or effect. The various factors which influence gut microbiome in patients with CRC and possible mechanism in relation with development of CRC. CONCLUSION: The clinical significance of the intestinal microbiota may aid in the prevention and management of CRC.

Evaluation of C4b as an adjunct marker in symptomatic RT-PCR negative Covid-19 cases.

Introduction: Detecting low viral load has been a challenge in this pandemic, which has led to its escalated transmission. Complement activation has been implicated in pathogenesis of Covid-19 infection. Thus, evaluation of complement activation in suspected Covid-19 infection may help to detect infection and limit false negative cases thus limiting transmission of infection. We speculate that measuring C4b, produced from an activated complement system due to the presence of Covid-19 may help in its detection, even when the viral titers are low. Methods: Plasma C4b levels of symptomatic RT-PCR positive patients (cases, n = 40); symptomatic RT-PCR negative patients (n = 35) and asymptomatic RT-PCR negative controls (n = 40) were evaluated. Plasma C5b-9, IL-6, D-dimer and C1-Inhibitor (C1-INH) were also measured in cases and controls. ELISA kits were used for all measurements. Statistical analyses were carried out using Stata, version 12 (Stata Corp., Texas, USA). Results: C4b levels were found to be significantly increased in RT-PCR positive patients as compared to asymptomatic RT-PCR negative controls. RT-PCR negative but symptomatic patients still showed increased C4b levels. The significantly higher levels of C4b in cases with a cut-off value of ≥ 116 ng/ml with optimum sensitivity and specificity of 80% and 52% respectively is indicative of its possible use as an adjunct marker. Increased levels of D-dimer, IL6, along with decreased levels of C1-INH were found in cases compared to controls. Whereas, C5b-9 levels were not significantly raised in cases. Conclusions: The results of our study suggests that plasma C4b may help to detect infection in false negative cases of RT-PCR that escape detection owing to low viral load. However, to confirm it a large-scale study is needed. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-022-01033-z.

Molecular approaches in cancer.

Cancer remains the second leading cause of death worldwide and newly diagnosed cases have increased at an alarming rate. One in every four people has a lifetime risk of being afflicted with cancer. Early diagnosis, which is essential in reducing morbidity and mortality, requires the development of highly sensitive and specific techniques to identify and monitor molecular changes for cancer-specific genetic and epigenetic markers. Among these, fluorescent in situ hybridization (FISH), Polymerase Chain Reaction (PCR), DNA microarray and NanoString technologies are notable. Recent advances in the development of efficient and cost-effective next-generation sequencing (NGS) has enabled whole genome, exome and transcriptome analysis. This review focuses on the features and applications of important molecular techniques to detect various genetic mutations thus enabling improved diagnosis, treatment and outcome.

A non-invasive miRNA-based approach in early diagnosis and therapeutics of oral cancer.

Oral or mouth cancer is the 16th most common form of cancer among the world's topmost malignancies. Healthy lifestyle and control of known risk factors can reduce its incidences further. Patients succumb to oral cancer when diagnosed late and lack timely access to tertiary care. Molecular biomarkers might help in early detection of oral cancer. Recently, researchers have identified numerous microRNAs which play a crucial role in promoting and suppressing oral cancers. miRNAs are short non-coding RNA molecules (18-22 nucleotides) that play a pivotal role in regulating gene expression. Understanding the miRNA interplays in oral cancers could augment the development of potential diagnostic, prognostic, and therapeutic tools. Liquid biopsy- a non-invasive approach that has been used lately, allows the determination of miRNAs in biological fluids that play essential roles in tumor suppression and cancer promotion. Herein, we summarize an update on the role of miRNAs in the diagnosis and treatment of oral cancer.

Molecular pathways in periampullary cancer: An overview.

Molecular alterations in oncogenes and tumor suppressors in various signaling pathways are basis for personalized therapy in cancer. Periampullary carcinoma behaves differently from pancreatic carcinoma both in prognosis and outcome, therefore it needs special attention. Pancreatic cancer have higher incidence of nodal spread and perineural &lymphovascular invasion suggesting it biologically more aggressive tumor compared to periampullary cancer. Since PAC tumors consist of heterogenous tissue of origin, they might contain different mutations in tumor associated genes and other changes in tissue composition among different subgroups clubbed together. Significant progress has been made in understanding the molecular nature of PAC in the previous two decades, and a large number of mutations and other genetic changes have been identified as being responsible for the disease. This review article targets to collate and discuss the molecular evolution of PAC and their implication in its outcome. As per literature, mitogen-activated protein kinase (MAPK), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), and Wnt signaling are the most common pathways involved in PAC. Mutations in KRAS, TP53, CTNNB1, SMAD4 and APC genes were the most frequently reported. I-subtype resembles colorectal cancer while the morphology of PB-type shows close resemblance to pancreatic tumors. The frequency of driver gene mutations is higher in I-type compared to PB-type of PAC indicating I-type to be genetically more unstable. The genetic landscape of PAC obtained from WES data highlighted PI3/AKT pathway to be a primary target in I-type and RAS/RAF in PB-type.