Li Salt Assisted Highly Flexible Carbonaceous Ni3N@polyimide Electrode for an Efficient Asymmetric Supercapacitor.

This work used a highly flexible, sustainable polyimide tape as a substrate to deposit ductile-natured carbonaceous Ni3N (C/Ni3N@polyimide) material for supercapacitor application. C/Ni3N was prepared using a co-sputtering technique, and this method also provided better adhesion of the electrode material over the substrate, which is helpful in improving bending performance. The ductile behavior of the sputter-grown electrode and the high flexibility of the polyimide tape provide ultimate flexibility to the C/Ni3N@polyimide-based supercapacitor. To achieve optimum electrochemical performance, a series of electrochemical tests were done in the presence of various electrolytes. Further, a flexible asymmetric supercapacitor (NC-FSC) (C/Ni3N//carbon@polyimide) was assembled by using C/Ni3N as a cathode and a carbon thin film as an anode, separated by a GF/C-glass microfiber soaked in optimized 1 M Li2SO4 aqueous electrolyte. The NC-FSC offers a capacitance of 324 mF cm-2 with a high areal energy density of 115.26 µWh cm-2 and a power density of 811 µW cm-2, with ideal bending performance.

GST polymorphism as a predictive biomarker for modulating the susceptibility to chronic obstructive pulmonary disease: A North Indian study.

Chronic obstructive pulmonary disease (COPD) is commonly characterized by shortness of breath, coughing or expectoration. Smoking is the leading cause of COPD development, but only a small percentage of smokers develop symptoms, implying a genetic component. Glutathione S-transferase enzymes are responsible for detoxifying cigarette smoke components. The role of glutathione S-transferase T1 (GSTT1) and glutathione S-transferase M1 (GSTM1) gene polymorphism was assessed with COPD susceptibility and associated clinical parameters in the North Indian population. This was a cross-sectional study involving 200 COPD patients and 200 healthy individuals, with peripheral blood sampling and adequate questionnaires. Multiplex PCR was used for genotyping GSTT1 and GSTM1 gene polymorphism. Logistic regression was used to calculate the odds ratio and 95% confidence intervals to assess the COPD risk and GST polymorphisms. The GSTT1 gene deletion rate was higher in COPD cases (34.5%) than in healthy individuals (20.5%). A statistical relationship between the GSTT1(-) null genotype and COPD risk was observed (odds ratio = 2.04, 95% CI = 1.30-3.20, P = 0.0019). After adjusting for covariates like age, sex and smoking status, a significant association was found for GSTT1(-) null genotype and COPD risk (adjusted odds ratio = 2.90, 95% CI = 1.43-5.87, P = 0.003). The GSTT1(-) genotype was also significantly correlated with clinical parameters for COPD risk. Another primary observation was that females with the GSTT1(-) null genotype were more vulnerable to COPD than males with the same gene deletion. The GSTT1(-) null genotype strongly correlates with COPD development, while no association was observed in the GSTM1(-) null genotype in the North Indian population.

Impact of ABCB1, ABCC1, ABCC2, and ABCG2 variants in predicting prognosis and clinical outcomes of north Indian lung cancer patients undergoing platinum-based doublet chemotherapy.

BACKGROUND: ABC transporters are membrane proteins expressed in the lungs and are crucial for efflux of various chemotherapeutic agents. Polymorphisms of ABC transporters have a certain impact on the transporter activity because their expression levels may influence the extent and longevity of chemotherapeutic drug outflow, affecting patient outcomes. The present study aimed to assess the impact of ABCB1, ABCC1/2, and ABCG2 gene variants in predicting prognosis and clinical outcomes in lung carcinoma patients. METHODS: In total, 502 lung cancer patients undergoing platinum-based chemotherapy were recruited in this prospective study. Genotyping of ABCB1 (C1236 T, C3435 T, and G2677 T/A), ABCC1 (G3173 A and G2168 A), ABCC2 (G4544 A), and ABCG2 (C421 A) polymorphisms in Northern Indian lung carcinoma patients were evaluated using polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: Poor survival outcomes were noted in patients carrying a heterozygous genotype (CT) for the ABCB1 C1236 T polymorphism compared to the wild-type genotype (CC) (p = 0.04). The mutant genotype (AA) for ABCC1 G3173 A exhibited a lower median survival time compared to the reference genotype (GG) (p = 0.009). Lower survival was observed in individuals carrying a heterozygous genotype (GA) for ABCC2 G4544 A polymorphism compared to the wild-type genotype (GG) (p = 0.017). Small cell lung cancer patients with the ABCB1 G2677 A polymorphism having a heterozygous genotype (GA) showed poor survival compared to the wild-type genotype (GG) (p = 0.03). For ABCC1 G3173 A, adenocarcinoma patients having a mutant genotype (AA) had reduced survival compared to the wild-type (GG) genotype (p = 0.03). For ABCB1 C3435 T, individuals carrying a heterozygous (CT) (p = 0.018) and mutant (TT) genotype (p = 0.007) had poor survival compared to the wild-type (CC) genotype in patients treated with pemetrexed and cisplatin. The patients administered cisplatin and irinotecan and having mutant alleles (AA) for the ABCB1 G2677 A polymorphism showed a lower survival compared to the individuals carrying wild-type alleles (GG) (p = 0.009). CONCLUSIONS: Our findings suggest that ABCB1 C1236 T, ABCB1 C3435 T, ABCB1 G2677 A, ABCC1 G3173 A, and ABCC2 G4544 A are involved in predicting prognosis. Genotyping of the ABC polymorphism is essential for predicting prognosis in lung carcinoma patients.

miRNAs are now starring in "No Time to Die: Overcoming the chemoresistance in cancer".

Cancer is a leading cause of death globally, with about 19.3 million new cases reported each year. Current therapies for cancer management include-chemotherapy, radiotherapy, and surgery. However, they are loaded with side effects and tend to cause toxicity in the patient's body posttreatment, ultimately hindering the response towards the treatment building up resistance. This is where noncoding RNAs such as miRNAs help provide us with a helping hand for taming the chemoresistance and providing potential holistic cancer management. MicroRNAs are promising targets for anticancer therapy as they perform critical regulatory roles in various signaling cascades related to cell proliferation, apoptosis, migration, and invasion. Combining miRNAs and anticancer drugs and devising a combination therapy has managed cancer well in various independent studies. This review aims to provide insights into how miRNAs play a mechanistic role in cancer development and progression and regulate drug resistance in various types of cancers. Furthermore, next-generation novel therapies using miRNAs in combination with anticancer treatments in multiple cancers have been put forth and how they improve the efficacy of the treatments. Exemplary studies currently in the preclinical and clinical models have been summarized. Ultimately, we briefly talk through the challenges that come forward with it and minimize them.

Role of thioredoxin in chronic obstructive pulmonary disease (COPD): a promising future target.

INTRODUCTION: Thioredoxin (Trx) is a secretory protein that acts as an antioxidant, redox regulator, anti-allergic, and anti-inflammatory molecule. It has been used to treat dermatitis and inflammation of the digestive tract. In the lungs, Trx has a significant anti-inflammatory impact. On the other hand, Chronic Obstructive Pulmonary Disease (COPD) is one of the significant causes of death in the developed world, with a tremendous individual and socioeconomic impact. Despite new initiatives and endless treatment trials, COPD incidence and death will likely escalate in the coming decades. AREAS COVERED: COPD is a chronic inflammatory disease impacting the airways, lung parenchyma, and pulmonary vasculature. Oxidative stress and protease-antiprotease imbalances are thought to be involved in the process. The most popular respiratory inflammatory and allergic disorders therapies are corticosteroids and ß-receptor agonists. These medications are helpful but have some drawbacks, such as infection and immunosuppression; thus, addressing Trx signalling treatments may be a viable COPD treatment approach. This review shall cover the pathophysiology of COPD, the pharmacognosy of anti-COPD drugs, including the assets and liabilities of each, and the role and mechanism of Trx in COPD treatment. EXPERT OPINION: Limited research has targeted the thioredoxin system as an anti-COPD drug. Spectating the increase in the mortality rates of COPD, this review article would be an interesting one to research.

Merging Electrochemical Synthesis and Post-Ugi Cyclization for the Synthesis of Diverse 4-Imidazolidinones.

Despite the appreciation for electro-organic synthesis, postmulticomponent reaction transformation chemistry rarely exploits this powerful technology. Herein, we explore post-Ugi cyclization reactions using N-centered radical-mediated intramolecular ipso cyclization to synthesize diverse spirocyclic variants of 4-imidazolidinones through the use of electrochemically generated amidyl radicals from the bis-amides of the Ugi adducts. This protocol features an undivided cell setup under constant-current conditions with carbon-platinum electrodes. These metal- and reagent-free reactions are scalable and have broad substrate scope.

Electrochemical Post-Ugi Cyclization for the Synthesis of Highly Functionalized Spirolactams.

The combination of the Ugi reaction and electro-organic synthesis can aid in the creation of novel heterocycles that have not been previously explored. In this study, a new strategy utilizing bis-amides from the Ugi reaction has been developed, which can produce C-S, C-Se, and C-C═O functionalized five-membered spirolactams mediated by electricity under catalyst- and metal-free conditions. Notably, this approach can be applied using a microelectro-flow reactor (µ-EFR) for gram-scale synthesis. The described strategy can synthesize complex azaspiro-fused tricyclic scaffolds with high diastereo- and regioselectivity, highlighting its versatility and potential.

Genetic variations in ABC transporter genes as a predictive biomarker for toxicity in North Indian lung cancer patients undergoing platinum-based doublet chemotherapy.

ATP-binding cassette (ABC) transporters are expressed in various human tissues and play a vital role in the efflux of various chemotherapeutic drugs. The current study has assessed genetic variants of ABCB1, ABCC1, ABCC2, and ABCG2 genes in 407 lung cancer patients undergoing platinum-based doublet chemotherapy. The association of ABCB1 (C1236 T, C3435 T, and G2677 T/A), ABCC1 (G3173 A and G2168 A),ABCC2 (G4544 A), and ABCG2 (C421 A) polymorphisms with chemotherapy-induced adverse events were assessed, and statistical analysis was conducted. Our data showed that patients harboring heterozygous (GA) genotype for ABCC1 G3173 A had an increased risk of developing leukopenia (odds ratio [OR] = 1.88, p = 0.04) and anemia (adjusted odds ratio [AOR] = 2.70, p = 0.03). For ABCC2 G4544 A polymorphism, patients harboring one copy of the mutant (GA) allele showed an increased risk of developing anemia (OR = 4.24, p = 0.03). After adjusting with various confounding factors, the heterozygous (GA) genotype showed a 5.63-fold increased risk of developing anemia (AOR = 5.63, p = 0.03). The ABCB1 G2677 A (OR = 0.37, p = 0.008) and ABCC1 G3173 A (OR = 0.54, p = 0.04) polymorphism showed a lower incidence of developing nephrotoxicity. In ABCG2 C421 A polymorphism, patients harboring heterozygous (CA) genotype had a lower incidence of having diarrhea (OR = 0.25, p = 0.04). An increased risk of having diarrhea was observed in the heterozygous genotype (GA) for ABCC1 G3173 A polymorphism (AOR = 2.78, p = 0.04). An increased risk of liver injury was found in the patients carrying heterozygous genotype of the ABCC1 G3173 A (OR = 2.06, p = 0.02) and ABCB1 C1236 T (OR = 1.85, p = 0.01). This study demonstrates the role of polymorphic variations in ABCB1, ABCC1, ABCC2, and ABCG2 in predicting hematological, nephrotoxicity, gastrointestinal, and hepatotoxicity.

Complications associated with subaxial placement of pedicle screws versus lateral mass screws in the cervical spine (C2-T1): systematic review and meta-analysis comprising 4,165 patients and 16,669 screws.

Lateral mass screw (LMS) and cervical pedicle screw (CPS) fixation are among the most popular techniques for posterior fusion of the cervical spine. Early research prioritized the LMS approach as the trajectory resulted in fewer neurovascular complications; however, with the incorporation of navigation assistance, the CPS approach should be re-evaluated. Our objective was to report the findings of a meta-analysis focused on comparing the LMS and CPS techniques in terms of rate of various complications with inclusion of all levels from C2 to T1. We conducted a systematic review of PubMed and EMBASE databases with final inclusion criteria focused on identifying studies that reported outcomes and complications for either the CPS or LMS technique. These studies were then pooled, and statistical analyses were performed from the cumulative data. A total of 60 studies comprising 4165 participants and 16,669 screws placed within the C2-T1 levels were identified. Within these studies, the LMS group had a significantly increased odds for lateral mass fractures (odds ratio [OR] = 43.2, 95% confidence interval [CI] = 2.62-711.42), additional cervical surgeries (OR = 5.56, 95%CI = 2.95-10.48), and surgical site infections (SSI) (OR = 5.47, 95%CI = 1.65-18.16). No other significant differences between groups in terms of complications were identified. Within the subgroup analysis of navigation versus non-navigation-guided CPS placement, no significant differences were identified for individual complications, although collectively significantly fewer complications occurred with navigation (OR = 5.29, 95%CI = 2.03-13.78). The CPS group had significantly fewer lateral mass fractures, cervical revision surgeries, and SSIs. Furthermore, navigation-assisted CPS placement was associated with a significant reduction in complications overall.

Association of IL4RA and IL-8 polymorphism in predicting susceptibility towards tuberculosis.

Mycobacterium tuberculosis is an infectious bacterial disease frequently affecting the lungs. With two fatalities from tuberculosis (TB) occurring every three minutes, India has the highest disease burden. The aetiology of tuberculosis has been linked to IL-8 and IL-4RA. Thus, the impact of the IL4RAQ576R and IL8 gene polymorphism on TB susceptibility was assessed. 301 healthy and 301 TB patients participated in a cross-sectional study. PCR RFLP was performed to identify the genotype of the IL4RAQ576R and IL-8 +781C/T gene polymorphism. The odds ratio and 95% confidence intervals were calculated using logistic regression to evaluate the risk of TB with IL4RAQ576R and IL-8 +781C/T polymorphism. A significant association was found between IL-4RA (p=0.04) and IL-8 +781 C/T (p= 0.03) in tuberculosis. Further, when clinical symptoms were compared with both polymorphisms, two of them, i.e., cough in IL-4RA576R (p=0.04) and breathlessness (p=0.01) in IL-8 +781C/T, showed a significant association. Moreover, different combinations of the SNPS were made, and the 3 risk allele shows a significant protective role (p=0.02). There is considerable evidence which shows that M. tuberculosis causes TB, an infectious disease that is genetically predisposed. The results of our study also showed that IL-4 RA Q576R and IL-8 +781 C/T played a significant protective function against tuberculosis, confirming the claim mentioned earlier. However, only the cough in IL-4RA576R and the dyspnea in IL-8 +781C/T exhibited a significant co-relation in TB patients when symptoms were examined. Additionally, the combined effects of the two SNPs were investigated, and it was discovered that the 3-risk allele has a strong association with tuberculosis. Therefore, the polymorphisms mentioned earlier, which may also be influenced by ethnicity, may significantly impact the chance of developing tuberculosis.

Polymorphism in Thymidylate Synthase Gene Predicts Survival and Toxicity in North Indian Lung Cancer Patients Undergoing Platinum-Based Doublet Chemotherapy.

BACKGROUND: With an estimated 1.8 million deaths, lung cancer is one of the widely reported malignancies, with substantial morbidity and mortality rates. Thymidylate synthase (TS) is an important drug target for platinum-based doublet chemotherapy as it is the only de novo source of thymidylate production in the cell. TS polymorphisms in the 5'UTR of Thymidylate synthase enhancer region (TSER) 2R/3R and 3'- UTR 1494del6 are investigated in this study. METHODS: A total of 700 lung cancer patients with platinum-based doublet chemotherapy were recruited in this study. TSER (2R/3R) and TS 1494del6 polymorphisms in North Indian lung cancer patients were examined, and statistical analysis was performed. RESULTS: According to our findings, patients with the wild genotype (2R/2R) for the TSER polymorphism had a longer median survival time as compared to patients harboring the mutant type genotype (3R/3R) [MST=9.77 vs. 7.57 months; p=0.04]. On the contrary, patients with the mutant 14946del6 polymorphism (-6/-6) had a longer survival time than patients with the wild-type genotype (+6/+6) [MST=7.23 vs. 9 months]. Further, our findings elucidated that the patients with heterozygous genotype (2R3R) for TSER polymorphism had a 2.30-fold increased risk of developing leukopenia (AOR=2.30, 95% CI=0.96-5.52; p=0.05). A substantial risk of 5.14-fold constipation was found in heterozygous genotype (2R3R) when intermediate grade 2 toxicity was compared with low toxicity (grade 1) (p=0.007).An increased risk of nausea/vomiting was observed in patients with mutant genotype (-6/-6bp) for 1494 ins/del6 polymorphism compared to patients with wild-type genotype (+6/+6bp) (AOR= 2.77; 95%CI=1.10-6.96, p=0.03). CONCLUSION: According to our findings, TSER and the 1494del6 polymorphism may operate as a prognostic marker in lung cancer patients receiving platinum-based chemotherapy. Furthermore, TS polymorphisms may influence the onset of platinum-related toxicity, such as hematological and gastrointestinal toxicity. These findings might facilitate therapeutic decisions for individualized therapy in lung cancer patients.

Electro-Oxidative sp3 C-H Bond Functionalization and Annulation Cascade: Synthesis of Novel Heterocyclic Substituted Indolizines.

Indolizine derivatives are prevalent in many synthetic intermediates, pharmaceuticals, and organic materials. Herein, we report a novel electro-oxidative cascade cyclization reaction that uses electricity as the primary energy input to promote the reaction, leading to a series of heterocyclic substituted indolizine derivatives under exogenous-oxidant-free conditions. It is noteworthy that this electrochemical method provides a novel strategy for generating heterocyclic diversity of quinazolinones and quinolines on indolizines. In addition, the sole byproduct in the reaction was molecular hydrogen.

Electrochemical Regioselective Sulfenylation of 2H-Indazoles with Thiols in Batch and Continuous Flow.

A novel electrochemical cross-dehydrogenative C-S bond coupling of aryl thiols with 2H-indazole is reported. Thiol-functionalized 2H-indazoles were synthesized under catalyst-, oxidant-, and metal-free conditions with innocuous hydrogen as the sole byproduct at ambient temperature. Furthermore, continuous electrochemical flow conditions using a graphite/Ni flow cell were used to obtained 3-(arylthio)-2H-indazole compounds on a gram scale within the residence time of 39 min. Detailed mechanistic studies including control experiments and cyclic voltammetry are provided to support the radical-radical cross-coupling pathway.

Genetic polymorphisms in the mismatch repair pathway (MMR) genes contribute to hematological and gastrointestinal toxicity in North Indian lung cancer patients treated with platinum-based chemotherapy.

The present study investigated the relationship between MLH1, MSH2, MSH3, and MSH6 polymorphisms and toxicity due to platinum-based doublet chemotherapy for North Indian lung cancer patients. Polymerase chain reaction-restriction fragment length polymorphism technique was used to assess the polymorphism. For MSH2 IVS1 + 9G > C polymorphism variant type genotype reported a 1.4-fold increased risk of anemia (AOR = 1.4; 95% CI = 0.98-1.99; p = 0.04) and decreased risk of developing gastrointestinal toxicity (diarrhea) (AOR = 0.53; 95% CI = 0.28-1.01; p = 0.04). Further, we also reported a 10-fold increased risk of developing severe grade anorexia in combined genotype (GC + CC) (AOR = 9.18; 95% CI = 0.98-86.1; p = 0.05). For MSH2 T > C/-6 polymorphism, variant type reported a 3-fold and 2-fold increased risk of developing severe grade leukopenia (AOR = 3.37; 95% CI = 1.44-7.88; p = 0.005) and neutropenia respectively (AOR = 2.23; 95% CI = 1.07-4.66; p = 0.03). For MSH3 G > A polymorphism, heterozygous (GA) and combined genotype (GA + AA) reported a 7-fold and 6-fold increased risk of developing anemia (AOR = 7.23; 95% CI = 1.51-34.6; p = 0.01, AOR = 6.39; 95% CI = 1.53-26.6; p = 0.01). Our results suggest that polymorphisms in DNA mismatch repair genes are associated with hematological, and gastrointestinal toxicities and might be considered a predictor for pretreatment evaluation in lung cancer patients.

Immunotherapy in Small Cell Lung Cancer Treatment: a Promising Headway for Future Perspective.

OPINION STATEMENT: Despite advancements in clinical research, both prognosis and treatment for SCLC patients are still in the nascent stage. SCLC is a fatal disease with high tumor mutational burden and is strongly associated with exposure to tobacco. This leads to the development of potential neo-antigens, inhibition of immune responses, and development of paraneoplastic disorders. Surgery, radiation, and chemotherapy are widely accepted treatments for cancer globally, and most recently, immunotherapy has now become the "fourth pillar" of SCLC treatment. Various immune checkpoint pathways regulate the activation of T cells at multiple stages during an immune response. T cell checkpoint inhibitors such as anti-PD1 (pembrolizumab, nivolumab), anti-PDL1, and anti-CTLA-4 (tremelimumab, ipilimumab) have potential to show anti-cancer activity along with the promise to prolong survival in patients with SCLC. Treatment with the CTLA-4-specific antibodies can restore the immune response by increasing the accumulation and survival of T-cells whereas monoclonal antibodies block either PD-1 or its ligands that prevent downregulation of effector T-cell, which enables the T-cells to mediate the death of tumor cells. Furthermore, monoclonal antibody in combination with chemotherapy has attained quite a focus to enhance the survival of SCLC patients. Apart from this, various immunotherapeutic approaches have been evaluated in the clinical trials for SCLC patients such as TLR9 agonist, anti-CD47, anti-ganglioside therapy, and anti-Notch signaling. The current review focuses on the rationale as well as on the clinical studies of immunotherapy in SCLC along with the clinical end results of certain immunotherapeutic agents and novel therapeutic combinations in SCLC patients.

Identification of SNPs in hMSH3/MSH6 interaction domain affecting the structure and function of MSH2 protein.

MutS homolog 2 (MSH2) is a mismatch repair gene that plays a critical role in DNA repair pathways, and its mutations are associated with different cancers. The present study aimed to find out the single nucleotide polymorphisms (SNPs) of MSH2 protein associated with causing structural and functional changes leading to the development of cancer with the help of computational tools. Four different tools for predicting deleterious SNPs (SIFT, PROVEAN, PANTHER, and PolyPhen), two tools each for identifying disease association (PhD-SNP and SNP&GO) and estimating stability (I-mutant and MUPro) were employed. Homology modeling, energy minimization, and root mean square deviation calculation were used to estimate structural variations. Twenty-seven SNPs and five SNPs (double amino acid change) were identified based on a consensus approach that might be associated with the structural and functional change in MSH2 protein. Molecular docking reveals that six SNPs affect the interaction of MSH2 and MSH6. Twelve identified SNPs were reported to be linked with hereditary nonpolyposis, colorectal cancer, and Lynch syndrome. Further, selected SNPs need to be validated in an in vitro system for their precise association with cancer predisposition.

Predictive role of polymorphic variants of phase II drug metabolising enzyme in modulating toxicity in North Indian lung cancer patients undergoing chemotherapy.

Genetic polymorphism of drug-metabolising enzymes such as NQO1, SULT1A1, EPHX1, and NAT2 alters its activity which hampers the detoxification and disposal of chemotherapeutic compounds. Thus, in the present study, we have comprehensively investigated the associations between SNPs of the Phase II detoxifying genes and its relationship towards platinum-induced toxicity of lung cancer patients.NQO1 (609 C > T), SULT1A1 (Arg213 His), EPHX1 (Tyr113His, His139Arg), and NAT2 (481 C > T, 803 A > G, 590 G > A, 857 G > A) were evaluated in our study for their associated adverse events caused due to the administration of platinum-based chemotherapy to the lung cancer patients.For NQO1 609 C > T polymorphism, the TT genotype showed reduced risk of constipation (OR = 0.10, p = 0.04) and anorexia (OR = 0.15, p = 0.03). For SULT1A1 Arg213His, heterozygous genotype (Arg/His) (AOR = 0.38, p = 0.006) and combined genotype (Arg/His + His/His) were not associated with increased risk of nephrotoxicity (AOR = 0.38, p = 0.004). For NAT2, heterozygous (NAT2*4/*6) and combined genotypes (NAT2*4/*4+*4/*6) for NAT2*6 polymorphism exhibit 2.4 folds (p = 0.005), and two-folds (p = 0.01) increased risk of hematological toxicity. The heterozygous (AOR = 0.45, p = 0.004) and variant genotype (AOR = 0.39, p = 0.02) for NAT2*5C had decreased risk for hematological toxicity. The heterozygous genotype for NAT2*7 polymorphism showed two-fold increased risk for developing thrombocytopenia.This study provides association of NAT2 polymorphic variants in predicting haematological toxicity.

Complications associated with subaxial placement of pedicle screws versus lateral mass screws in the cervical spine: systematic review and meta-analysis comprising 1768 patients and 8636 screws.

Lateral mass screw (LMS) fixation for the treatment of subaxial cervical spine instability or deformity has been traditionally associated with few neurovascular complications. However, cervical pedicle screw (CPS) fixation has recently increased in popularity, especially with navigation assistance, because of the higher pullout strength of the pedicle screws. To their knowledge, the authors conducted the first meta-analysis comparing the complication rates during and/or after CPS and LMS placement for different pathologies causing cervical spine instability. A systematic literature search of PubMed and Embase from inception to January 12, 2021 was performed to identify studies reporting CPS and/or LMS-related complications. Complications were categorized into intraoperative and early postoperative (within 30 days of surgery) and late postoperative (after 30 days from surgery) complications. All studies that met the prespecified inclusion criteria were pooled and cumulatively analyzed. A total of 24 studies were conducted during the time frame of the search and comprising 1768 participants and 8636 subaxially placed screws met the inclusion criteria. The CPS group experienced significantly more postoperative C5 palsy (odds ratio [OR] = 3.48, 95% confidence interval [CI] = 1.27-9.53, p < 0.05). Otherwise, there were no significant differences between the LMS and CPS groups. There were no significant differences between the CPS and LMS groups in terms of neurovascular procedure-related complications other than significantly more C5 palsy in the CPS group.

Polymorphisms in solute carrier genes (SLC19A1, SLCO1B1, and SLCO1B3) predicts survival and toxicity in North Indian lung cancer patients undergoing platinum-based doublet chemotherapy.

WHAT IS KNOWN AND OBJECTIVE: Solute Carrier (SLC) transporters are known mediators of drug disposition that facilitate the influx of substrates and various chemotherapeutic agents into cells. Polymorphisms in the SLC19A1, SLCO1B1, and SLCO1B3 gene influence the prognosis in the cancer patients, but little is known about their role in lung cancer in Asians. So, the current study aims to investigate the polymorphisms in SLC19A1, SLCO1B1, and SLCO1B3 genes in Northern Indian lung cancer patients. METHODS: Patients with lung cancer who had a confirmed histology and cytology diagnosis were enrolled in the study. SLC polymorphisms were assessed by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) for variations in SLC19A1 (G80 A), SLCO1B1 (A388 G, T521 C), and SLCO1B3 (A1683-5676 G). RESULTS AND DISCUSSION: Our results showed that mutant genotype for SLC19A1 G80 A polymorphism had higher median survival time (MST) compared to wild genotype. ADCC patients with mutant genotype showed better survival compared to wild genotype for SLC19A1 G80 A. SCLC patients G80 A polymorphism showed increased survival in patients with mutant genotype (p = 0.04). In SLCO1B3, A1683-5676 G patients carrying heterozygous alleles and administered with platinum and docetaxel showed inferior survival (p = 0.006). In T521 C variant, patients with carrier genotype had reduced chances of developing anaemia (p = 0.04). Patients with SLC19A1 and SLCO1B3 variants showed lower incidence of thrombocytopenia and nephrotoxicity. WHAT IS NEW AND CONCLUSION: Our findings imply that Solute Carrier gene polymorphisms modulate the overall survival in lung cancer patients undergoing platin-based doublet chemotherapy, also these polymorphisms have a modifying impact on the associated adverse events/toxicity.

Synergistic polymorphic interactions of phase II metabolizing genes and their association toward lung cancer susceptibility in North Indians.

Lung cancer is a multifactorial carcinoma with diverse heterogeneity. Genetic variations in drug-metabolizing enzymes may lead to defective detoxification and clearance of carcinogenic compounds. The high-order gene-gene interaction has been carried out between different genotypes of Phase II detoxification genes (NQO1, SULT1A1, NAT2, and EPHX1). Our results depict the genetic combination of SULT1A1 R213H with NAT2 × 5B L161L, SULT1A1 R213H with NAT2 × 5C K268R, EPHX1 H139R and NAT2 × 5B L161L exhibit a protective effect towards lung cancer risk. Further, the triple combinations of NQO1 P187S, EPHX1 Y113H, and EPHX1 H139R; NQO1 P187S, EPHX1 Y113H, and NAT2 × 6 R197Q; NQO1 P187S, EPHX1 Y113H, and NAT2 × 7 G286E; SULT1A1 R213H, EPHX1 H139R, and NAT2 × 7 G286E suggested a two-fold increased risk of lung cancer for subjects. Genetic polymorphisms of phase II detoxifying genes (NAT2, NQO1, EPHX1, SULT1A1) are prognostic markers for lung cancer.