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.

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.

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.

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.

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.

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.

Randomized trial drug controlled compendious transcriptome analysis supporting broad and phase specific therapeutic potential of multiple candidates in COVID-19.

Effective therapies for coronavirus disease 2019 (COVID-19) are urgently needed. Maladaptive hyperinflammation and excessive cytokine release underlie the disease severity, with antiinflammatory and cytokine inhibiting agents expected to exert therapeutic effects. A major present challenge is identification of appropriate phase of the illness for a given intervention to yield optimum outcomes. Considering its established disease biomarker and drug discovery potential, a compendious analysis of existing transcriptomic data is presented here toward addressing this gap. The analysis is based on COVID-19 data related to intensive care unit (ICU) and non-ICU admissions, discharged and deceased patients, ventilation and non-ventilation phases, and high oxygen supplementation. It integrates transcriptomic data related to the effects of, in various cellular treatment models, the COVID-19 randomized clinical trial (RCT) successful drug dexamethasone, and the failed drug, with a potential to harm, hydroxychloroquine/chloroquine. Similarly, effects of various COVID-19 candidate drugs/anticytokines as well as proinflammatory cytokines implicated in the illness are also examined. The underlying assumption was that compared to COVID-19, an effective drug/anticytokine and a disease aggravating agent would affect gene regulation in opposite and same direction, in that order. Remarkably, the assumption was supported with respect to both the RCT drugs. With this control validation, etanercept, followed by tofacitinib and adalimumab, showed transcriptomic effects predictive of benefits in both ventilation and non-ventilation ICU stages as well as in non-ICU phase. On the other hand, canakinumab showed potential for effectiveness in high oxygen supplementation phase. These findings may inform experimental and clinical studies toward drug repurposing in COVID-19.

Paternal inheritance of diet induced metabolic traits correlates with germline regulation of diet induced coding gene expression.

Inheritance of induced traits through the germline is poorly understood and controversial. The ideal evidence correlating induced and inherited traits with germline gene expression remains largely obscure. Using a Drosophila coding transcriptome level model of paternal high sugar diet induced alterations in triglyceride levels across generations, in conjunction with pre-existing data, we show here highly significant overlap of differentially expressed genes between the ancestral generation, the resulting sperm and embryos, and the future generation individuals. Further, gene ontology and literature-wide overrepresentation analysis reveal association of lipid and carbohydrate metabolism, and immune response, besides others, with differentially expressed genes in the above samples. Analysis of available mouse data on inheritance of diet induced metabolic traits also revealed a similar correlation. Our results support a causal role of sperm borne mRNAs in inheritance of acquired characteristics, consistent with the evidence that these mRNAs are delivered to the oocyte and influence embryonic development.

Multifaceted genome-wide study identifies novel regulatory loci in SLC22A11 and ZNF45 for body mass index in Indians.

Obesity, a risk factor for multiple diseases (e.g. diabetes, hypertension, cancers) originates through complex interactions between genes and prevailing environment (food habit and lifestyle) that varies across populations. Indians exhibit a unique obesity phenotype with high abdominal adiposity for a given body weight compared to matched white populations suggesting presence of population-specific genetic and environmental factors influencing obesity. However, Indian population-specific genetic contributors for obesity have not been explored yet. Therefore, to identify potential genetic contributors, we performed a two-staged genome-wide association study (GWAS) for body mass index (BMI), a common measure to evaluate obesity in 5973 Indian adults and the lead findings were further replicated in 1286 Indian adolescents. Our study revealed novel association of variants-rs6913677 in BAI3 gene (p = 1.08 × 10-8) and rs2078267 in SLC22A11 gene (p = 4.62 × 10-8) at GWAS significance, and of rs8100011 in ZNF45 gene (p = 1.04 × 10-7) with near GWAS significance. As genetic loci may dictate the phenotype through modulation of epigenetic processes, we overlapped genetic data of identified signals with their DNA methylation patterns in 236 Indian individuals and performed methylation quantitative trait loci (meth-QTL) analysis. Further, functional roles of discovered variants and underlying genes were speculated using publicly available gene regulatory databases (ENCODE, JASPAR, GeneHancer, GTEx). The identified variants in BAI3 and SLC22A11 genes were found to dictate methylation patterns at unique CpGs harboring critical cis-regulatory elements. Further, BAI3, SLC22A11 and ZNF45 variants were located in repressive chromatin, active enhancer, and active chromatin regions, respectively, in human subcutaneous adipose tissue in ENCODE database. Additionally, these genomic regions represented potential binding sites for key transcription factors implicated in obesity and/or metabolic disorders. Interestingly, GTEx portal identify rs8100011 as a robust cis-expression quantitative trait locus (cis-eQTL) in subcutaneous adipose tissue (p = 1.6 × 10-7), and ZNF45 gene expression in skeletal muscle of Indian subjects showed an inverse correlation with BMI indicating its possible role in obesity. In conclusion, our study discovered 3 novel population-specific functional genetic variants (rs6913677, rs2078267, rs8100011) in 2 novel (SLC22A11 and ZNF45) and 1 earlier reported gene (BAI3) for BMI in Indians. Our study decodes key genomic loci underlying obesity phenotype in Indians that may serve as prospective drug targets in future.

Biosynthesized composites of Au-Ag nanoparticles using Trapa peel extract induced ROS-mediated p53 independent apoptosis in cancer cells.

The current study highlights rapid, sustainable, and cost-effective biosynthesis of silver (Ag), gold (Au) nanoparticles (NPs), and bimetallic Au-AgNPs composites using bio-waste extract of Trapa natans. Growth of the NPs was monitored spectrophotometrically and peak was observed at ∼525 nm, ∼450 nm, and ∼495 nm corresponding to Plasmon absorbance of AuNPs, AgNPs, and Au-AgNPs, respectively. Transmission electron microscopy (TEM) revealed the size of AgNPs (∼15 nm), AuNPs (∼25 nm), and Au-AgNPs (∼26-90 nm). Synthesized NPs follow the Gaussian bell curve and its crystalline nature was identified by X-ray diffraction (XRD). Furthermore, Au-AgNPs induced cytotoxicity in various cancer cells (HCT116, MDA-MB-231, and HeLa) effectively at 200 µg/mL. Au-AgNPs-exposed cancer cells exhibited apoptotic features such as nuclear condensation, mitochondrial membrane potential loss, and cleavage of casp-3 and poly (ADP-ribose) polymerase-1 (PARP). Au-AgNPs exposure enhanced reactive oxygen species (ROS) and upon inhibition of ROS, apoptosis was reduced effectively. NPs treatment killed HCT116 WT and p53 knockout cells without any significant difference. Mechanistically, Au-AgNPs derived with Trapa peel extract significantly enhance ROS which trigger p53-independent apoptosis in various cancer cells effectively. Our study explores the use of bio-waste for the green synthesis of NPs, which can be attractive candidates for cancer therapy.

Ethosuximide Induces Hippocampal Neurogenesis and Reverses Cognitive Deficits in an Amyloid-ß Toxin-induced Alzheimer Rat Model via the Phosphatidylinositol 3-Kinase (PI3K)/Akt/Wnt/ß-Catenin Pathway.

Neurogenesis involves generation of new neurons through finely tuned multistep processes, such as neural stem cell (NSC) proliferation, migration, differentiation, and integration into existing neuronal circuitry in the dentate gyrus of the hippocampus and subventricular zone. Adult hippocampal neurogenesis is involved in cognitive functions and altered in various neurodegenerative disorders, including Alzheimer disease (AD). Ethosuximide (ETH), an anticonvulsant drug is used for the treatment of epileptic seizures. However, the effects of ETH on adult hippocampal neurogenesis and the underlying cellular and molecular mechanism(s) are yet unexplored. Herein, we studied the effects of ETH on rat multipotent NSC proliferation and neuronal differentiation and adult hippocampal neurogenesis in an amyloid ß (Aß) toxin-induced rat model of AD-like phenotypes. ETH potently induced NSC proliferation and neuronal differentiation in the hippocampus-derived NSC in vitro. ETH enhanced NSC proliferation and neuronal differentiation and reduced Aß toxin-mediated toxicity and neurodegeneration, leading to behavioral recovery in the rat AD model. ETH inhibited Aß-mediated suppression of neurogenic and Akt/Wnt/ß-catenin pathway gene expression in the hippocampus. ETH activated the PI3K·Akt and Wnt·ß-catenin transduction pathways that are known to be involved in the regulation of neurogenesis. Inhibition of the PI3K·Akt and Wnt·ß-catenin pathways effectively blocked the mitogenic and neurogenic effects of ETH. In silico molecular target prediction docking studies suggest that ETH interacts with Akt, Dkk-1, and GSK-3ß. Our findings suggest that ETH stimulates NSC proliferation and differentiation in vitro and adult hippocampal neurogenesis via the PI3K·Akt and Wnt·ß-catenin signaling.

Systems genomics analysis centered on epigenetic inheritance supports development of a unified theory of biology.

New discoveries are increasingly demanding integration of epigenetics, molecular biology, genomic networks and physiology with evolution. This article provides a proof of concept for evolutionary transgenerational systems biology, proposed recently in the context of epigenetic inheritance in mammals. Gene set enrichment analysis of available genome-level mammalian data presented here seem consistent with the concept that: (1) heritable information about environmental effects in somatic cells is communicated to the germline by circulating microRNAs (miRNAs) or other RNAs released in physiological fluids; (2) epigenetic factors including miRNA-like small RNAs, DNA methylation and histone modifications are propagated across generations via gene networks; and (3) inherited epigenetic variations in the form of methylated cytosines are fixed in the population as thymines over the evolutionary time course. The analysis supports integration of physiology and epigenetics with inheritance and evolution. This may catalyze efforts to develop a unified theory of biology.

Bioinformatic analysis revealing association of exosomal mRNAs and proteins in epigenetic inheritance.

Transgenerational inheritance of environment induced phenotype requires transmission of epigenetic information through the germline. Whereas several epigenetic factors have been implicated in germline transmission, mediators of information transfer from soma to the germline remain unidentified in mammals. Notably, a recent bioinformatic analysis showed association of extracellular microRNAs (miRNAs) and altered transcriptomes in diverse instances of mammalian epigenetic inheritance involving different environmental factors, tissues, life cycle stages, generations and genders. It was predicted that regulatory non-coding RNAs (ncRNAs) may potentially mediate soma to germline information transfer. Remarkably, the present bioinformatic evidence suggests similar association of exosomal mRNAs and proteins. The differentially expressed genes reported previously in genome level expression profiling studies related to or relevant in epigenetic inheritance showed enrichment for documented set of exosomal mRNAs in a few instances of epigenetic inheritance and of exosomal proteins in a majority of instances. Differentially expressed genes encoding exosomal miRNAs and proteins, directly or indirectly through first and/or second degree interactome networks, overrepresented biological processes related to environmental factors used in these instances as well as to epigenetic alterations, especially chromatin and histone modifications. These findings predict that exosomal mRNAs and proteins, like extracellular miRNAs, may also potentially mediate soma to germline information transfer. A convergent conceptual model is presented wherein extracellular ncRNAs/miRNA, mRNAs and proteins provide the much needed continuum inclusive of epigenetic inheritance. The phrase "transgenerational systems biology" is introduced to signify that the realm of systems biology extends beyond an individual organism and encompasses generations.

Video-assisted thoracoscopic surgery retrieval of a migrated unilateral hypoglossal nerve stimulator sensor lead.

Obstructive sleep apnea is a common chronic condition typically treated with positive airway pressure. However, many patients have difficulty with adherence to this therapy, and for some, implantation of a hypoglossal nerve stimulator has become an option. Though device implantation is generally well-tolerated, a minority of patients will experience serious adverse events. Here we report the unusual complication of the sensor lead migrating to the costophrenic angle and invading the pleural space. Nine months after original implantation, the sensor lead malfunctioned and was found to be displaced. Initial explantation and reimplantation of a new device resulted in the inability to find a portion of the lead. Reimaging showed the missing lead at the costophrenic angle, and the patient underwent thoracoscopic removal. He resumed therapy with the new device without difficulty. This case demonstrates the ability of the lead to migrate far from the implantation site, which has rarely been reported.

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.

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.

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.

Palate Shape, Drug-Induced Sleep Endoscopy Findings, and Obstructive Sleep Apnea Pharyngeal Surgery Outcomes.

OBJECTIVE: Pharyngeal surgery is a treatment option for patients with obstructive sleep apnea (OSA) unable to tolerate positive pressure therapy. This study aims to determine the association between palate shape as described by Woodson and pharyngeal surgical outcomes. STUDY DESIGN: Exploratory analysis of retrospective cohort. SETTING: Multicenter. METHODS: Three blinded reviewers assessed palate shape using drug-induced sleep endoscopy (DISE) videos from a previously-assembled cohort of adults undergoing pharyngeal surgery. Palate shape scores were examined for association with surgical outcomes with univariate and multivariate analyses. Multivariate analyses included adjustment for consensus DISE findings determined previously. RESULTS: Two hundred nine study subjects were included from 13 centers. Age was 53.7 ± 11.5 years, body mass index (BMI) was 30.3 ± 5.0 kg/m2, and 21% were female. In isolated soft palate surgery, greater GenuAP narrowing was associated with lesser odds of surgical response, whereas greater GenuLW narrowing was associated with greater odds of surgical response. These findings largely persisted after adjustment for key DISE findings, age, gender, OSA severity, BMI, and tonsil size. Other palate-shape findings were not clearly associated with surgical outcomes, although some palate-shape findings demonstrated trends toward an association with outcomes (P < .10). CONCLUSION: Greater GenuAP narrowing and GenuLW narrowing were associated with lesser and greater, respectively, odds of surgical response after isolated soft palate surgery. Palate shape and other palate shape level scores were not clearly associated with surgical outcomes. Larger studies may determine more precisely the association between palate shape and pharyngeal surgery outcomes.