Evaluating the Utility of Liver Transaminases as Predictors of Feto-Maternal Outcome in Lieu of Serum Bile Acids in Intrahepatic Cholestasis of Pregnancy: A Prospective Observational Study.

Introduction: Intrahepatic Cholestasis of Pregnancy (ICP) is a disorder of the second half of pregnancy causing pruritus and abnormal liver function tests (LFT). Incidence in India is 1.2-1.5%. ICP leads to adverse feto-maternal outcomes with early delivery indicated before serum bile acids (SBA) (gold standard) and hepatic transaminases are critically high. With paucity of evidence these levels are not well defined. Objectives: To determine the association of liver transaminases with pregnancy outcomes in ICP and evaluate critical levels for prediction of adverse outcomes. Material and Methods: A prospective observational study was conducted comprising 88 pregnant women with pruritus not associated with rash. After history and examination, LFT and SBA levels were done, treatment given and followed till pregnancy termination to determine the feto-maternal outcome. Results: The mean age of participants was 26.43 ± 3.35 years. The mean SBA, ALT and AST levels were 18.97 ± 10.320 µmol/L, 206.06 ± 45.71units/litre and 175.37 ± 101.088 units/litre respectively. 39.7% of participants were symptomatic for ICP while 38.6% responded to treatment. 34.1% underwent LSCS majorly (43.3%) formeconiumand 23.3% had foetal distress. 33% had preterm delivery. 5.68% of the neonates needed NICU admission and 6.8% had respiratory distress syndrome. The cut off for ALT on ROC curve analysis was 151.5 units/litre with AUC as 0.905, sensitivity and specificity of 89.7 and 70% respectively. Conclusion: ICP leads to adverse pregnancy outcomes. ALT is a promising predictor of adverse outcome and termination of pregnancy can be planned accordingly.

An intercontinental comparison of the influence of smoking on the occurrence of nonsyndromic cleft lip and palate: a meta-analysis and systematic review.

BACKGROUND: The influence of smoking on nonsyndromic clefts has been a topic of research for many years. However, few studies have investigated the effect of smoking on causing clefts in different gene pools. METHODS: A meta-analysis was conducted of case-control studies related to smoking. Keywords such as "clefts," "cleft lip," "cleft palate," "orofacial cleft," and "smoking" were used to search the MEDLINE, Embase, and Cochrane databases. RESULTS: In total, 51 articles were reviewed. The RevMan software was utilized for the analysis, and the Mantel-Haenszel method was employed to pool the odds ratios (ORs) and 95% confidence intervals. Although the overall OR, a measure of the association between exposure and outcome, was higher for smokers than for non-smokers, this association was significantly stronger in individuals from Asia and South America (1.73), and lowest in Europe (1.31). Among active and passive smokers in Asia, the OR was approximately 0.93, indicating an equivalent impact from both types of smoking. CONCLUSION: This analysis indirectly suggests that restriction measures targeting both active and passive smoking are crucial in Asia.

3D microscaffolds with triple-marker sensitive nanoprobes for studying fatty liver disease in vitro.

Non-alcoholic fatty liver disease (NAFLD) is a heterogeneous condition that encompasses a wide range of liver diseases that progresses from simple hepatic steatosis to the life-threatening state of cirrhosis. However, due to the heterogeneity of this disease, comprehensive analysis of several physicochemical and biological factors that drive its progression is necessary. Therefore, an in vitro platform is required that would enable real-time monitoring of these changes to better understand the progression of these diseases. The earliest stage of NAFLD, i.e. hepatic steatosis, is characterised by triglyceride accumulation in the form of lipid vacuoles in the cytosol of hepatocytes. This fatty acid accumulation is usually accompanied by hepatic inflammation, leading to tissue acidification and dysregulated expression of certain proteases such as matrix metalloproteinases (MMPs). Taking cues from the biological parameters of the disease, we report here a 3D in vitro GelMA/alginate microscaffold platform encapsulating a triple-marker (pH, MMP-3 and MMP-9) sensitive fluorescent nanoprobe for monitoring, and hence, distinguishing the fatty liver disease (hepatic steatosis) from healthy livers on the basis of pH change and MMP expression. The nanoprobe consists of a carbon nanoparticle (CNP) core, which exhibits intrinsic pH-dependent fluorescence properties, decorated either with an MMP-3 (NpMMP3) or MMP-9 (NpMMP9) sensitive peptide substrate. These peptide substrates are flanked with a fluorophore-quencher pair that separates on enzymatic cleavage, resulting in fluorescence emission. The cocktail of these nanoprobes generated multiple fluorescence signals corresponding to slightly acidic pH (blue) and overexpression of MMP-3 (green) and MMP-9 (red) enzymes in a 3D in vitro fatty liver model, whereas no/negligible fluorescence signals were observed in a healthy liver model. Moreover, this platform enabled us to mimic fatty liver disease in a more realistic manner. Therefore, this 3D in vitro platform encapsulating triple-marker sensitive fluorescent nanoprobes would facilitate the monitoring of the changes in pH and MMP expression, thereby enabling us to distinguish a healthy liver from a diseased liver and to study liver disease stages on the basis of these markers.

Anti-dengue therapeutic potential of Tinospora cordifolia and its bioactives.

ETHNOPHARMACOLOGICAL RELEVANCE: Dengue is one of the most prevalent mosquito-borne viral infections. Moreover, due to the absence of appropriate curative and preventive measures against it, the mortality rate is increasing alarmingly. However, remarkable docking and clinical advances have been achieved with plant-based natural and conventional therapeutics. Tinospora cordifolia is one of the highly explored panaceas at the local level for its effective anti-dengue formulations. AIM OF THE STUDY: The present article aims for critical assessment of the data available on the anti-dengue therapeutic use of T. cordifolia. Efforts have also been made on the clinical and in-silico anti-dengue efficacy of this plant. The phytochemistry and the antiviral machinery of the plant are also emphasized. MATERIALS AND METHODS: The present article is the outcome of the literature survey on the anti-dengue effect of T. cordifolia. A literature survey was conducted from 2011 to 2024 using different databases with appropriate keywords. RESULTS: The present study confirms the anti-dengue potential of T. cordifolia. The plant can suppress the initiation of 'cytokine storm', vascular leakage and inhibition of various structural and NS proteins to exert its anti-dengue potential. Berberine and magnoflorine phytocompounds were highly explored for their anti-dengue potential. CONCLUSIONS: The present study concluded that T. cordifolia serves as an effective therapeutic agent for treating dengue. Further in-silico and clinical studies are needed so that stable, safe and efficacious anti-dengue drug can be developed. Besides, a precise antiviral mechanism of T. cordifolia against DENV infection is still needed.

Association of the Antidepressants and the Periodontal Status: An Original Research.

Antidepressants have anti-inflammatory effects and boost immunity, and dentists should be aware. This case-control study included only those patients who consented to take part and had a ham-d score of at least 16 and a diagnosis of moderate-to-severe depression. Inclusion criteria included adults, those experiencing moderate to severe depression, taking fluoxetine or venlafaxine, and those with twenty or more teeth. Exclusion criteria included tobacco chewers, smokers, women expecting or nursing, periodontal treatment, antibiotics, anti-inflammatory medication, or vitamin/nutritional supplements. Patients who had had surgery or other therapy were excluded from the study. Three groups of patients were created: Control, venlafaxine, and fluoxetine. A periodontist assisted in the dental examination, and indices were observed. The analysis was done using Statistical Package for the Social Sciences (SPSS) version 24.0. Number, percentage, mean, and standard deviation were used to present the values. Results showed that antidepressants may be a risk factor for periodontal health, with increased periodontal parameters, and concluded that It is crucial to frequently check the periodontal health of depressed people using fluoxetine or venlafaxine since these drugs put good periodontal tissues at risk.

Desymmetric homologating annulation to access chiral pentafulvenes and their application in bioimaging.

The architectural design of polycyclic/multisubstituted pentafulvenes has demonstrated great potential for the development of electrochromic materials and biologically active motifs. Unfortunately, the enantioselective construction of such distinctive cores with all carbon quaternary chiral centers has remained untouched to date. Herein, we disclose an enantioselective homologating annulation of cyclopent-4-ene-dione with 3-cyano-4-methylcoumarins through L-tert-leucine derived thiourea catalysis, affording a wide range of enantioenriched polycyclic multisubstituted embedded aminopentafulvenes with excellent stereocontrol (up to 99:1 er) and chemical yields up to 87%. A detailed photophysical and cytotoxicity analysis of racemic and chiral homologated adducts unveils the exceptional behavior of chiral adducts over their racemic analogs, highlighting the importance of stereoselectivity of the developed scaffolds. A cellular uptake experiment in a mammalian fibroblast cell line confirmed the potential of developed polycyclic aminopentafulvene cores as a highly promising labeling dye that can be utilized for bioimaging without any adverse effects.

Endotracheal Tube Size Adjustments Within Seven Days of Neonatal Intubation.

BACKGROUND AND OBJECTIVES: Neonatal endotracheal tube (ETT) size recommendations are based on limited evidence. We sought to determine data-driven weight-based ETT sizes for infants undergoing tracheal intubation and to compare these with Neonatal Resuscitation Program (NRP) recommendations. METHODS: Retrospective multicenter cohort study from an international airway registry. We evaluated ETT size changes (downsizing to a smaller ETT during the procedure or upsizing to a larger ETT within 7 days) and risk of procedural adverse outcomes associated with first-attempt ETT size selection when stratifying the cohort into 200 g subgroups. RESULTS: Of 7293 intubations assessed, the initial ETT was downsized in 5.0% of encounters and upsized within 7 days in 1.5%. ETT downsizing was most common when NRP-recommended sizes were attempted in the following weight subgroups: 1000 to 1199 g with a 3.0 mm (12.6%) and 2000 to 2199 g with a 3.5 mm (17.1%). For infants in these 2 weight subgroups, selection of ETTs 0.5 mm smaller than NRP recommendations was independently associated with lower odds of adverse outcomes compared with NRP-recommended sizes. Among infants weighing 1000 to 1199 g: any tracheal intubation associated event, 20.8% with 2.5 mm versus 21.9% with 3.0 mm (adjusted OR [aOR] 0.62, 95% confidence interval [CI] 0.41-0.94); severe oxygen desaturation, 35.2% with 2.5 mm vs 52.9% with 3.0 mm (aOR 0.53, 95% CI 0.38-0.75). Among infants weighing 2000 to 2199 g: severe oxygen desaturation, 41% with 3.0 mm versus 56% with 3.5mm (aOR 0.55, 95% CI 0.34-0.89). CONCLUSIONS: For infants weighing 1000 to 1199 g and 2000 to 2199 g, the recommended ETT size was frequently downsized during the procedure, whereas 0.5 mm smaller ETT sizes were associated with fewer adverse events and were rarely upsized.

Rapid Electrochemical Detection of Bacterial Sepsis in Cirrhotic Patients: A Microscaffold-Based Approach for Early Intervention.

Sepsis is a dysregulated inflammatory response leading to multiple organ failure. Current methods of sepsis detection are time-consuming, involving nonspecific clinical signs, biomarkers, and blood cultures. Hence, efficient and rapid sepsis detection platforms are of utmost need for immediate antibiotic treatment. In the current study, a noninvasive rapid monitoring electrochemical sensing (ECS) platform was developed for the detection and classification of plasma samples of patients with liver cirrhosis by measuring the current peak shifts using the cyclic voltammetry (CV) technique. A total of 61 hospitalized cirrhotic patients with confirmed (culture-positive) or suspected (culture-negative) sepsis were enrolled. The presence of bacteria in the plasma was observed by growth kinetics, and for rapidness, the samples were co-encapsulated in microscaffolds with carbon nanodots that were sensitive enough to detect redox changes occurring due to the change in the pH of the surrounding medium, causing shifts in current peaks in the voltammograms within 2 h. The percentage area under the curve for confirmed infections was 94 and that with suspected cases was 87 in comparison to 69 and 71 with PCT, respectively. Furthermore, the charge was measured for class identification. The charge for LPS-absent bacteria ranged from -400 to -600 µC, whereas the charge for LPS-containing bacteria class ranged from -290 to -300 µC. Thus, the developed cost-effective system was sensitive enough to detect and identify bacterial sepsis.

Ubiquitin specific peptidase (USP37) mediated effects in microscaffold-encapsulated cells: a comprehensive study on growth, proliferation and EMT.

Though significant advances have been made in developing therapeutic strategies for cancer, suitable in vitro models for mechanistically identifying relevant drug targets and understanding disease progression are still lacking. Most studies are generally performed using two-dimensional (2D) models, since these models can be readily established and allow high throughput assays. However, these models have also been reported as the reason for unreliable pre-clinical information. To avoid this discrepancy, three-dimensional (3D) cell culture models have been established and have demonstrated the potential to provide alternative ways to study tissue behavior. However, most of these models first require optimization and cell cultures with a certain density, thus adding a prepping step in the platform before it can be used for any studies. This limits their use in studies where the fundamental understanding of biological processes must be carried out in a short time frame. In this study, we developed a 3D cell culture system that tests a less explored cancer therapeutic target-the deubiquitinating enzyme ubiquitin specific peptidase 37 (USP37)-in different cancer cell lines using sensitive carbon dot pH nanosensors, which provides a rapid model for studies compared to the parallel model available commercially. This enzyme is found to be elevated in different cancers and has been reported to play a role in cell cycle regulation, oncogenesis and metastasis. However, the confirmation of the role of USP37 downregulation in cellular proliferation via appropriate in vitro 3D models has not been demonstrated. To establish the applicability of the developed 3D platform in studying such oncogenes, classical 2D models have been used in this study for identifying the role of USP37 in tumor progression and metastasis. The data clearly suggests that this ingeniously developed 3D cell culture system is a better alternative to 2D models to study the growth and migration of different cancer cell lines on depletion of oncogenic proteins like USP37 and its effect on epithelial-mesenchymal transition (EMT) markers, and it can further be targeted as a viable therapeutic option.

Dual-Sensitive Fluorescent Nanoprobes for Simultaneously Monitoring In Situ Changes in pH and Matrix Metalloproteinase Expression in Stiffness-Tunable Three-Dimensional In Vitro Scaffolds.

A tumor microenvironment often presents altered physicochemical characteristics of the extracellular matrix (ECM) including changes in matrix composition, stiffness, protein expression, pH, temperature, or the presence of certain stromal and immune cells. Of these, overexpression of matrix metalloproteinases (MMPs) and extracellular acidosis are the two major hallmarks of cancer that can be exploited for tumor detection. The change in matrix stiffness and the release of certain cytokines (TNF-α) in the tumor microenvironment play major roles in inducing MMP-9 expression in cancerous cells. This study highlights the role of mechanical cues in upregulating MMP-9 expression in cancerous cells using stiffness-tunable matrix compositions and dual-sensitive fluorescent nanoprobes. Ionically cross-linked 3D alginate/gelatin (AG) scaffolds with three stiffnesses were chosen to reflect the ECM stiffnesses corresponding to healthy and pathological tissues. Moreover, a dual-sensitive nanoprobe, an MMP-sensitive peptide conjugated to carbon nanoparticles with intrinsic pH fluorescence properties, was utilized for in situ monitoring of the two cancer hallmarks in the 3D scaffolds. This platform was further utilized for designing a 3D core-shell platform for spatially mapping tumor margins and for visualizing TNF-α-induced MMP-9 expression in cancerous cells.

A decellularized matrix enriched collagen microscaffold for a 3D in vitro liver model.

The development of liver scaffolds retaining their three-dimensional (3D) structure and extra-cellular matrix (ECM) composition is essential for the advancement of liver tissue engineering. We report the design and validation of an alginate-based platform using a combination of decellularized matrices and collagen to preserve the functionality of liver cells. The scaffolds were characterized using SEM and fluorescence microscopy techniques. The proliferation and functional behaviours of hepatocellular carcinoma HuH7 cells were observed. It was found that the decellularized skin scaffold with collagen was better for maintaining the growth of cells in comparison to other decellularized matrices. In addition, we observed a significant increase in the functional profile once exogenous collagen was added to the liver matrix. Our study also suggests that a cirrhotic liver model should have a different matrix composition as compared to a healthy liver model. When primary rat hepatocytes were used for developing a healthy liver model, the proliferation studies with hepatocytes showed a decellularized skin matrix as the better option, but the functionality was only maintained in a decellularized liver matrix with addition of exogenous collagen. We further checked if these platforms can be used for studying drug induced toxicity observed in the liver by studying the activation of cytochrome P450 upon drug exposure of the cells growing in our model. We observed a significant induction of the CYP1A1 gene on administering the drugs for 6 days. Thus, this platform could be used for drug-toxicity screening studies using primary hepatocytes in a short span of time. Being a microscaffold based system, this platform offers some advantages, such as smaller volumes of samples, analysing multiple samples simultaneously and a minimal amount of decellularized matrix in the matrix composition, making it an economical option compared to a completely dECM based platform.

Associations among gene polymorphisms, crestal bone loss, and bone mineral density in patients receiving dental implants.

Objectives: Interleukin 1 (IL-1) and interleukin 6 (IL-6) gene polymorphisms have been suggested to be responsible for diminished bone mineral density (BMD) and high crestal bone loss (CBL) in some individuals. However, the effects of systemic BMD on variations in peri-implant CBL are unclear. Hence, this study was aimed at investigating the association of IL-1 and IL-6 gene polymorphisms with systemic BMD and CBL around dental implants. Methods: A total of 190 participants undergoing dental implantation in the mandibular posterior region were selected according to predetermined selection criteria and divided into a normal BMD group (NBD, 93 participants, T-score ≥ -1) and low BMD group (LBD, including both osteoporosis and osteopenia, 97 participants, T-score < -1 standard deviation) according to the BMD of the right femoral neck, measured with dual-energy X-ray absorptiometry. Dental implants were placed through the standard surgical protocol, and CBL was calculated after 6 months with cone beam computed tomography scans before second-stage surgery. Genotyping was performed on all participants for IL-1A-889 A/G, IL-1B-511G/A, IL-1B+3954, and IL-6-572 C/G gene polymorphisms. Results: The demographic and clinical characteristics of the participants in both groups were compared with t-test and chi-square test (χ2). The associations of NBD and LBD with the different genotypes and CBL was determined with odds ratios, and p < 0.05 was considered statistically significant. The frequency of IL-1B-511AA and IL-6-572 GG genotypes was significantly higher in LBD than in NBD (p < 0.05). In LBD, the IL-1B-511 AA (AA vs GA + GG; p ≤ 0.001) and IL-6-572 GG (GG vs CC + GC; p = 0.001) genotypes were significantly associated with higher peri-implant CBL. Conclusions: Individuals with the IL-1B-511 AA or IL-6-572 GG genotype had elevated risk of osteoporosis/osteopenia and were more susceptible to CBL around dental implants.

Revolution of nanotechnology in food packaging: Harnessing electrospun zein nanofibers for improved preservation - A review.

Zein, a protein-based biopolymer derived from corn, has garnered attention as a promising and eco-friendly choice for packaging food due to its favorable physical attributes. The introduction of electrospinning technology has significantly advanced the production of zein-based nanomaterials. This cutting-edge technique enables the creation of nanofibers with customizable structures, offering high surface area and adjustable mechanical and thermal attributes. Moreover, the electrospinning process allows for integrating various additives, such as antioxidants, antimicrobial agents, and flavoring compounds, into the zein nanofibers, enhancing their functionalities for food preservation. In this comprehensive review, the various electrospinning techniques employed for crafting zein-based nanofibers, and we delve into their enhanced properties. Furthermore, the review illuminates the potential applications of zein nanofibers in active and intelligent packaging materials by incorporating diverse constituents. Altogether, this review highlights the considerable prospects of zein-based nanocomposites in the realm of food packaging, offering sustainable and innovative solutions for food industry.

Vitamin D intervention as a curative measure for glucose intolerance in obese children and adolescents: a systematic review on randomized control trials.

Vitamin D deficiency is associated with obesity and its associated metabolic disorders, as specified in many epidemiological studies. The assertion that vitamin D can mitigate insulin insensitivity in obese children and adolescents lacks adequate empirical substantiation. Thus, the study utilized some clinical trials on vitamin D interventions to examine the impact of vitamin D supplementation on insulin resistance in obese children and adolescents. The literature was extracted by applying the PRISMA method through electronic databases such as Scopus, Science Direct, Medline, the Cochrane Library, and PubMed from 2012 to 2022. All the articles were in English, and the inclusion criteria for each article were based on the study design and the anthropometric and biochemical parameters of the subjects. A total of 572 research articles were acquired, out of which only seven closely adhered to the inclusion criteria of the study. The studies in this systematic review are based on randomized control trials. The age range of the children in this study spans from 2 to 19 years, and the follow-up period ranges from 3 to 12 months. The range of daily vitamin D doses provided varied from 2000 to 10,000 IU. The results indicate that four randomized controlled trials have demonstrated a positive impact on glycemic parameters, such as insulin levels, fasting blood sugar, and insulin resistance, in the subjects following vitamin D treatment. However, the three trials did not provide sufficient evidence to support a statistically significant effect. CONCLUSION: The present review highlights that a significant proportion of the studies incorporated in the analysis demonstrate that the administration of vitamin D may be a preventive measure in ameliorating insulin resistance among pediatric patients with obesity, but it is advisable to implement a prolonged intervention with a substantial sample size and perform micro-level analysis at the gene level to evaluate the impact of vitamin D treatment. WHAT IS KNOWN: • Childhood obesity and its associated metabolic disorder is a concerned global problem. • Several studies showed an association of vitamin D deficiency with adiposity- induced metabolicdisorders which are still controversial. This study focused on finding interlink between vitamin Dsupplementation with obesity induced insulin resistance in children and adolescents. WHAT IS NEW: • This study supports that high dosage of Vitamin D in long term may be protective against insulinresistance in obese paediatric individuals. • A new factor is also reported in the study that vitamin D may alter the composition of gut microbiotawhich represents a compelling approach to the therapeutic management of obesity and diabetes.

Comparison of colorimetric, spectroscopic and electrochemical techniques for quantification of hydrogen sulfide.

Background: Hydrogen sulfide (H2S), an endogenous gasotransmitter, has potential applications in several conditions. However, its quantification in simulated physiological solutions is a major challenge due to its gaseous nature and other physicochemical properties. Aim: This study was designed to compare four commonly used H2S detection and quantification methods in aqueous solutions. Methods: The four techniques compared were one colorimetric, one chromatographic and two electrochemical methods. Results: Colorimetric and chromatographic methods quantified H2S in millimolar and micromole ranges, respectively. The electrochemical methods quantified H2S in the nanomole and picomole ranges and were less time-consuming. Conclusion: The H2S quantification method should be selected based on the specific requirements of a research project in terms of sensitivity, response time and cost-effectiveness.

A Miniaturized, Low-Frequency Magnetoelectric Wireless Power Transfer System for Powering Biomedical Implants.

This work experimentally demonstrates the operation of a miniaturized magnetoelectric (ME) wireless power transfer (WPT) system by incorporating a ME transducer and a suitable interface power management circuit (PMC) for potentially powering implantable medical devices (IMD) wirelessly. A ME heterostructure is micromachined to obtain desired device dimensions of 3.5 × 5 mm 2 and to restrict the operating frequency at a clinically approved frequency of 50 kHz. The proposed work also aims to address the trade-off between the device miniaturization, power attenuation and limiting the specific absorption rate (SAR) in the human tissue. By limiting the operating frequency to 50 kHz, the SAR is reduced to less than 1 µW/kg. The fabricated device is characterized with low-intensity AC magnetic field up to 40 µT without using any DC bias, resulting in 0.4 V output voltage and 6.6 µW power across 8 k Ω load. Alignment misorientation between the Tx and Rx is studied for in-plane and out-of-plane angular rotations to confirm the device's reliability against angular misalignment. By eliminating the bulky biasing magnets, the proposed device achieves a significant size reduction compared to the previously reported works. In addition, a self-powered interface PMC is incorporated with the ME system. The PMC generates 3.5 V regulated DC voltage from the input AC voltage range 0.7 V to 3.3 V. The PMC is fabricated on a 2-layered PCB and the over all ME WPT system consumes 12 × 12 mm 2 area. The overall PMC has intrinsic current consumption less than 550 nA with peak power conversion efficiency higher than 85 %. The in vitro cytotoxicity analysis in the human hepatic cell line WRL-68 confirmed the biocompatibility of the Parylene-C encapsulated ME device for up to 7 days, suggesting its potential use in implantable electronic devices for biomedical and clinical applications.

Combination of image-guided IMRT and IGBT in locally advanced carcinoma cervix: Prospective evaluation of toxicities and clinical outcomes from a tertiary cancer center in India.

Purpose: We aimed to assess the toxicity profile and clinical outcome in patients with locally advanced cervical cancer (LACC) treated with a combination of image-guided intensity-modulated radiation therapy (IG-IMRT) and image-guided brachytherapy (IGBT). Material and methods: 25 LACC patients were recruited in this single-arm prospective study. Whole pelvis IG-IMRT was delivered (45 Gy with simultaneously integrated nodal boost of 55 Gy in 25 fractions), with concurrent weekly cisplatin (40 mg/m2). Patients received IGBT of 7 Gy each in 4 fractions to high-risk clinical target volume (HR-CTV). First fraction was done under MRI, and subsequent fractions were performed under CT guidance. Primary endpoint was acute toxicity, and secondary endpoints were 2-year loco-regional control and late toxicity. Results: The median age was 52 years, and FIGO 2018 stage distribution was IIA2, IIB, IIIB, and IIIC1 in 12%, 40%, 20%, and 28% patients, respectively. All patients received concurrent chemotherapy with median number of 5 cycles (range, 4-5 cycles). Grade 1 and 2 diarrhea, and grade 1 cystitis was reported in 4 (16%), 3 (12%), and 2 (8%) patients, respectively. Grade 1 and 2 anemia, and grade 1 and 2 dermatitis were observed in 3 (12%) and 2 (8%), and 3 (12%) and 3 (12%) patients, respectively. No patient reported grade 3-4 acute toxicity. At median follow-up of 29.5 months (range, 25-37 months), late grade 1 bladder toxicity was observed in 1 (4%) patient. Loco-regional control at 1 and 2 years were 96% and 92%, respectively. Conclusions: The combination of IG-IMRT and IGBT yielded excellent outcomes in terms of acute toxicity and loco-regional control.

Electrochemical synthesis and antimicrobial evaluation of some N-phenyl α-amino acids.

In the present report, the authors describe a synthetic route for the generation of N-phenyl amino acid derivatives using CO2via a C-C coupling reaction in an undivided cell containing a combination of Mg-Pt electrodes. The reactions were completed in a short time without the formation of any other side product. The final products were purified via a simple recrystallization procedure. The structures of the newly prepared compounds were established using advanced spectroscopic techniques including 1H, 13C NMR, IR, and ESI-MS. All the prepared derivatives show good-to-excellent activity when tested against bacterial and fungal strains. Interestingly, it was observed that the presence of polar groups (capable of forming H-bonds) such as -OH (4d) and -NO2 (4e) at the para position of the phenyl ring show activity equivalent to the standard drugs.

Generation of Patterned Cocultures in 2D and 3D: State of the Art.

Cells inside the body are embedded into a highly structured microenvironment that consists of cells that lie in direct or close contact with other cell types that regulate the overall tissue function. Therefore, coculture models are versatile tools that can generate tissue engineering constructs with improved mimicking of in vivo conditions. While there are many reviews that have focused on pattering a single cell type, very few reviews have been focused on techniques for coculturing multiple cell types on a single substrate with precise control. In this regard, this Review covers various technologies that have been utilized for the development of these patterned coculture models while mentioning the limitations associated with each of them. Further, the application of these models to various tissue engineering applications has been discussed.

Liver Extracellular Matrix-Based Nanofiber Scaffolds for the Culture of Primary Hepatocytes and Drug Screening.

Immortalized liver cell lines and primary hepatocytes are currently used as in vitro models for hepatotoxic drug screening. However, a decline in the viability and functionality of hepatocytes with time is an important limitation of these culture models. Advancements in tissue engineering techniques have allowed us to overcome this challenge by designing suitable scaffolds for maintaining viable and functional primary hepatocytes for a longer period of time in culture. In the current study, we fabricated liver-specific nanofiber scaffolds with polylactic acid (PLA) along with a decellularized liver extracellular matrix (LEM) by the electrospinning technique. The fabricated hybrid PLA-LEM scaffolds were more hydrophilic and had better swelling properties than the PLA scaffolds. The hybrid scaffolds had a pore size of 38 ± 8 µm and supported primary rat hepatocyte cultures for 10 days. Increased viability (2-fold increase in the number of live cells) and functionality (5-fold increase in albumin secretion) were observed in primary hepatocytes cultured on the PLA-LEM scaffolds as compared to those on conventional collagen-coated plates on day 10 of culture. A significant increase in CYP1A2 enzyme activity was observed in hepatocytes cultured on PLA-LEM hybrid scaffolds in comparison to those on collagen upon induction with phenobarbital. Drugs like acetaminophen and rifampicin showed the highest toxicity in hepatocytes cultured on hybrid scaffolds. Also, the lethal dose of these drugs in rodents was accurately predicted as 1.6 g/kg and 594 mg/kg, respectively, from the corresponding IC50 values obtained from drug-treated hepatocytes on hybrid scaffolds. Thus, the fabricated liver-specific electrospun scaffolds maintained primary hepatocyte viability and functionality for an extended period in culture and served as an effective ex vivo drug screening platform to predict an accurate in vivo drug-induced hepatotoxicity.