Temporal trends in indoor bioaerosols: implications for dental healthcare environments.

Antibiotic resistance, a significant public health hazard, is predicted to cause 10 million deaths worldwide by 2050. The study aimed to identify culturable bioaerosols in the indoor air of dental units in Lahore and assess their antibiotic resistance. Air samples were collected from 10 dental unit locations at different distances, with average concentrations of fungi and bacteria falling within intermediate ranges, per the Global Index of Microbial Contamination (GIMC/m3) index. The study found higher antibiotic-resistant strains in hospital dental units, particularly during winter. The most vigorous strain, S.aureus-NAJIH18, exhibited 70% resistance to ceftazidime. The research highlights the importance of quantifying microbial pollutants for evaluating their source and complexity. It suggests proactive mitigation techniques, such as focused cleaning and air filtration, to improve indoor air quality can mitigate the spread of antibiotic-resistant strains. These insights offer hope in combating the growing public health threat of antibiotic resistance.

Treatment Outcomes of Incidental Gallbladder Cancer - Results from a High-Volume Tertiary Care Centre in North India.

Gallbladder cancer (GBC) is a lethal disease. Incidentally detected gallbladder cancer (IGBC) presents a unique opportunity for early management and better outcomes. We present the institutional experience of a high-volume tertiary care center in northern India. Retrospective analysis of a prospectively maintained database was performed and data of all IGBC patients between January 2014 to December 2021 was analyzed. There were 125 patients of IGBC among the 750 patients of GBC seen during the study period. Of these 125 patients, 72 (57.6%) patients were not eligible for surgery. Successful completion radical cholecystectomy (CRC) was possible in 37 (69.8%) of the 53 patients who underwent surgery. On univariate analysis, thickness of gallbladder wall 10 mm or more (p < 0.001, OR 19.0, 95% CI 4.58-78.76), pathological stage (p < 0.001, OR 5.8, 95% CI 2.45-14.98) and median delay of 16 weeks or more (p < 0.001, OR 17.0, 95% CI = 4.08-70.76), were associated with inoperability. However, on multivariate analysis only gallbladder wall thickness of 10 mm or more (p < 0.001, AOR 17.9, 95% CI 3.24-98.78) and median delay of 16 weeks or more (p < 0.001, AOR 32.33, 95% CI 6.05-172.66) remained significant. Median time to recurrence (TTR) and overall survival (OS) was not reached after a median follow up of 30 months in patients undergoing successful CRC. Successful outcomes of IGBC are dependent on several factors. Diligent workup of suspicious thickening before simple cholecystectomy for gallstone disease and timely referral of IGBC to tertiary care are the keystones for good outcomes.

Cancer stem cell biomarkers SOX2 and Oct4 in cervical cancer patients undergoing chemoradiotherapy.

BACKGROUND: Cancer stem cell biomarkers SRY (sex-determining region Y)-box 2 (SOX2) and octamer-binding transcription factor 4 (Oct4) account for radioresistance in cervical squamous cell cancers (CSCCs). Their clinical implications are limited and contradictory. METHODS: In this prospective cohort study, we recruited patients with FIGO IB2-IVA CSCC treated with primary chemoradiotherapy on regular follow-up. Tissue biopsy specimens were evaluated for SOX2 and Oct4 expression by immunohistochemistry, quantified by a product of proportion and intensity scores. RESULTS: A total of 59 patients were included. Most had a moderately differentiated (81%), keratinizing (59%) CSCC, and ≥FIGO stage IIB disease (95%). SOX2 expression (high:low 21:38 patients) and Oct4 expression (high:low 4:55 patients) had a significant interrelation (p = 0.005, odds ratio (95% CI) - 1.23 (1.004-1.520)). At a median follow-up of 36 months, the 3-year overall survival (OS) was 60% and 53% for low and high SOX2 expression (p = 0.856), and 54% and 100% for low and high Oct4 expression (p = 0.114). The 3-year disease-frese survival (DFS) was 65% and 50% in the low and high SOX2 expression (p = 0.259), and 59% and 75% for low and high Oct4 expression (p = 0.598). SOX2 expression was the only variable significantly associated with a lower OS and DFS on regression analysis. CONCLUSION: Our study demonstrated a trend toward improved OS and DFS with low SOX2 and high Oct4 expression in CSCC patients undergoing chemoradiotherapy.

Efficacy of decentralised home-based antihypertensive treatment in older adults with multimorbidity and polypharmacy (ATEMPT): an open-label randomised controlled pilot trial.

BACKGROUND: Older patients with multimorbidity and polypharmacy have been under-represented in clinical trials. We aimed to assess the effect of different intensities of antihypertensive treatment on changes in blood pressure, major safety outcomes, and patient-reported outcomes in this population. METHODS: ATEMPT was a decentralised, two-armed, parallel-group, open-label randomised controlled pilot trial conducted in the Thames Valley area, South East England. Individuals aged 65 years or older with multimorbidity (three or more chronic conditions) or polypharmacy (five or more types of medications) and a systolic blood pressure of 115-165 mm Hg were eligible for inclusion. Participants were identified through a search of national hospital discharge databases, identification of patients registered with an online pharmacy, and via targeted advertising on social media platforms. Participants were randomly assigned to receive up to two more classes versus up to two fewer classes of antihypertensive medications. Apart from routine home visits for conducting the baseline assessment, all communication, monitoring, and management of participants by the trial team was conducted remotely. The primary outcome was change in home-measured blood pressure. FINDINGS: Between Dec 15, 2020, and Aug 31, 2022, 230 participants were randomly assigned (n=126 to more vs n=104 to fewer antihypertensive medications). The frequency of serious adverse events was similar across both groups; no cardiovascular events occurred in the more antihypertensive drugs group, compared with six in the fewer antihypertensive drugs group, of which two were fatal. Over a 13-month follow-up period, the mean systolic blood pressure in the group allocated to receive more antihypertensive medications decreased from 134·5 mm Hg (SD 10·7) at baseline to 122·1 mm Hg (10·5). By contrast, in the group allocated to receive fewer antihypertensive medications, it remained relatively unchanged, moving from 134·8 mm Hg (SD 11·2) at baseline to 132·9 mm Hg (15·3); this corresponded to a mean difference of -10·7 mm Hg (95% CI -17·5 to -4·0). INTERPRETATION: Remotely delivered antihypertensive treatment substantially reduced systolic blood pressure in older adults who are often less represented in trials, with no increase in the risk of serious adverse events. The results of this trial will inform a larger clinical trial focusing on assessing major cardiovascular events, safety, physical functioning, and cognitive function that is currently in the planning stages. These results also underscore the efficiency of decentralised trial designs, which might be of broader interest in other settings. FUNDING: National Institute for Health Research Oxford Biomedical Research Centre and the Oxford Martin School.

Silver-cored Ziziphus spina-christi extract-loaded antimicrobial nanosuspension: overcoming multidrug resistance.

Aims: To synthesize a silver-cored nanosuspension utilizing Ziziphus spina-christi fresh-leaf extract and evaluate their antimicrobial activity against multidrug-resistant pathogenic microbes. Materials and Methods: The prepared nanosuspension was analyzed by spectro-analytical techniques and tested for antimicrobial activity and resistance to biofilm formation. The leaf extract and nanosuspension were tested separately and together as a mixture. Results: Constituent nanoparticles were average-sized (∼34 nm) and were active against both Gram-positive and Gram-negative microbes and yeast. Candida albicans showed a 24.50 ± 1.50 mm inhibition zone, followed by Escherichia coli and Staphylococcus aureus. Increased bioactivity with the highest multifold increments, 150%, for erythromycin against all tested microbes was observed. Carbenicillin and trimethoprim showed 166%- and 300%-fold increments for antimicrobial activity against Pseudomonas aeruginosa, respectively. Conclusion: The nanosuspension exhibited strong potential as an antimicrobial agent and overcame multidrug resistance.

Ziziphus spina-christi leaf extract-coated silver nanoparticles were synthesized using an environment-friendly method, and the preparation was effective against Escherichia coli, Staphylococcus aureus and Candida albicans. The prepared formulation showed increased antimicrobial activity at a 150­300% increase compared with leaf extract-only activity. The prepared suspension was also active against Pseudomonas aeruginosa, the multidrug-resistant microbe, and has the potential to treat drug-resistant microbial infections.

U-Pb zircon geochronology and geochemistry of Luk Ulo River boulders belong to Late Cretaceous-Paleocene metapsammite and metagranite of Luk Ulo Karangsambung, Central Java, Indonesia.

The rock formation of late Cretaceous-Paleocene metapsammite and metagranite found across Luk Ulo Complex indicated boulders with diameter of approximately 1 m and rounded shape along Luk Ulo River, Indonesia. However, less research found on geochronology and geochemistry has been conducted in study area, and such rocks require comprehensive understanding of magmatism and tectonic environment of Central Java, Indonesia. Therefore, the main objective of this study is to address the geochemical and geochronological age histories across Central Java, Indonesia, using U-Pb zircon dating technique. Generally, most common types of rocks were observed which composed of hornblende and garnet-bearing metapsammite and metagranite. The geochemical study showed that protolith of rocks with hornblende was identified as Cordilleran granitoid (I-type), which originated from magmatic arc with basaltic differentiation. Furthermore, protolith of rocks containing garnet was categorized as Caledonian granitoid (S-type), which is caused by post-collisional orogeny. The cluster observations of magmatic zircons reveal their magmatic ages, which vary from 67.00 ± 1.2 to 69.10 ± 0.91 Ma (late Cretaceous), whereas ages of inherited zircons ranged from 100 ± 5 to 437 ± 13 Ma (early Cretaceous to Silurian). Estimated periods of partial melting were found between 100 ± 5 Ma and 118 ± 4 Ma (early Cretaceous). Comparing the zircon ages of Luk Ulo with the zircon ages from the Sundaland regions reveals that the age distribution patterns are incredibly similar; the peak ages dispersed between the Cretaceous and Triassic periods, as well as Sundaland region was the source of the materials.

Formulation Development, Optimization by Box-Behnken Design, and In Vitro and Ex Vivo Characterization of Hexatriacontane-Loaded Transethosomal Gel for Antimicrobial Treatment for Skin Infections.

There are many different infections and factors that can lead to skin illnesses, but bacteria and fungi are the most frequent. The goal of this study was to develop a hexatriacontane-loaded transethosome (HTC-TES) for treating skin conditions caused by microbes. The HTC-TES was developed utilizing the rotary evaporator technique, and Box-Behnken design (BBD) was utilized to improve it. The responses chosen were particle size (nm) (Y1), polydispersity index (PDI) (Y2), and entrapment efficiency (Y3), while the independent variables chosen were lipoid (mg) (A), ethanol (%) (B), and sodium cholate (mg) (C). The optimized TES formulation with code F1, which contains lipoid (mg) (A) 90, ethanol (%) (B) 25, and sodium cholate (mg) (C) 10, was chosen. Furthermore, the generated HTC-TES was used for research on confocal laser scanning microscopy (CLSM), dermatokinetics, and in vitro HTC release. The results of the study reveal that the ideal formulation of the HTC-loaded TES had the following characteristics: 183.9 nm, 0.262 mV, -26.61 mV, and 87.79% particle size, PDI, and entrapment efficiency, respectively. An in vitro study on HTC release found that the rates of HTC release for HTC-TES and conventional HTC suspension were 74.67 ± 0.22 and 38.75 ± 0.23, respectively. The release of hexatriacontane from TES fit the Higuchi model the best, and the Korsmeyer-Peppas model indicates the release of HTC followed a non-Fickian diffusion. By having a higher negative value for cohesiveness, the produced gel formulation demonstrated its stiffness, whereas good spreadability indicated better gel application to the surface. In a dermatokinetics study, it was discovered that TES gel considerably increased HTC transport in the epidermal layers (p < 0.05) when compared to HTC conventional formulation gel (HTC-CFG). The CLSM of rat skin treated with the rhodamine B-loaded TES formulation demonstrated a deeper penetration of 30.0 µm in comparison to the hydroalcoholic rhodamine B solution (0.15 µm). The HTC-loaded transethosome was determined to be an effective inhibitor of pathogenic bacterial growth (S. aureus and E. coli) at a concentration of 10 mg/mL. It was discovered that both pathogenic strains were susceptible to free HTC. According to the findings, HTC-TES gel can be employed to enhance therapeutic outcomes through antimicrobial activity.

Differential Effect of Heat Stress on Drought and Salt Tolerance Potential of Quinoa Genotypes: A Physiological and Biochemical Investigation.

Soil salinity, drought, and increasing temperatures are serious environmental issues that drastically reduce crop productivity worldwide. Quinoa (Chenopodium quinoa Willd) is an important crop for food security under the changing climate. This study examined the physio-biochemical responses, plant growth, and grain yield of four quinoa genotypes (A7, Titicaca, Vikinga, and Puno) grown in pots containing normal (non-saline) or salt-affected soil exposed to drought and elevated-temperature treatments. Combinations of drought, salinity, and high-temperature stress decreased plant growth and yield more than the individual stresses. The combined drought, salinity, and heat stress treatment decreased the shoot biomass of A7, Puno, Titicaca, and Vikinga by 27, 36, 41, and 50%, respectively, compared to that of control plants. Similar trends were observed for grain yield, chlorophyll contents, and stomatal conductance. The combined application of these three stresses increased Na concentrations but decreased K concentrations in roots and shoots relative to control. Moreover, in the combined salinity, drought, and high-temperature treatment, A7, Puno, Titicaca, and Vikinga had 7.3-, 6.9-, 8-, and 12.6-fold higher hydrogen peroxide contents than control plants. All four quinoa genotypes increased antioxidant enzyme activities (CAT, SOD, and POD) to overcome oxidative stress. Despite A7 producing the highest biomass under stress, it did not translate into increased grain production. We conclude that Puno and Titicaca are more tolerant than Vikinga for cultivation in salt-affected soils prone to drought and heat stress.

Uniportal video-assisted thoracoscopic surgery in semi-prone position utilising direct endobronchial intubation for oesophagus leiomyoma excision.

Leiomyomas are the most common benign tumours of oesophageal smooth muscle origin. In this era of constantly evolving medical technology, video-assisted, robot-assisted and endoscopic approaches are the minimally invasive strategies for the excision of these lesions. Here, we report our modification of this surgery. The lesion was excised with uniportal video-assisted thoracoscopic surgery in a semi-prone position with single-lumen endobronchial intubation.

Nanotechnology - A new frontier of nano-farming in agricultural and food production and its development.

The potential of nanotechnology for the development of sustainable agriculture has been promising. The initiatives to meet the rising food needs of the rapidly growing world population are mainly powered by sustainable agriculture. Nanoparticles are used in agriculture due to their distinct physicochemical characteristics. The interaction of nanomaterials with soil components is strongly determined in terms of soil quality and plant growth. Numerous research has been carried out to investigate how nanoparticles affect the growth and development of plants. Nanotechnology has been applied to improve the quality and reduce post-harvest loss of agricultural products by extending their shelf life, particularly for fruits and vegetables. This review assesses the latest literature on nanotechnology, which is used as a nano-biofertilizer as seen in the agricultural field for high productivity and better growth of plants, an important source of balanced nutrition for the crop, seed germination, and quality enrichment. Additionally, post-harvest food processing and packaging can benefit greatly from the use of nanotechnology to cut down on food waste and contamination. It also critically discusses the mechanisms involved in nanoparticle absorption and translocation within the plants and the synthesis of green nanoparticles.

Discovery of Novel Isonipecotic Acid-Based Heteroaryl Amino Acid Derivatives as Potential Anticonvulsant Agents: Design, Synthesis, In-Silico ADME Study, and Molecular Docking Studies.

Background: Epilepsy is a neurological disorder characterized by anomalous brain activity, convulsions, and odd behavior. Several substituted-(naphthalen-2-yl)-3-(1H-indol-3-yl) allyl)-1,4-dihydropyridine-4-carboxylic acid derivatives (5a-j) were intended to be produced in the current research effort to reduce convulsions and seizures. Materials and Methods: The newly developed compounds were produced by the prescribed process. Numerous methods (infrared spectroscopy (IR), nuclear magnetic resonance (NMR), mass, elemental analysis, etc.) were used to characterize these substances. Several models were used to test each of these molecules for anticonvulsant activity. By using the rotarod and ethanol potentiation techniques, neurotoxicity was also evaluated. The study meticulously examined each parameter and showed absorption, distribution, metabolism, and excretion (ADME) predictions for each of the 10 congeners that were produced. In addition, studies on molecular docking employed the gamma amino butyric acid (GABA)-A target protein. Results: Anticonvulsant screening results identified compounds 5f, 5h, 5d, and 5b as the most efficacious of the series. All synthesized equivalents largely passed the neurotoxicity test. The results of molecular docking revealed significant interactions at the active site of GABA-A with LEU B: 99, TYR A: 62, Ala A: 174, and THR B: 202, and the outcomes were good and in agreement with in vivo findings. Conclusions: The study's findings showed that some substances had promising anticonvulsant properties that were comparable to those of the standard drug. The highly active novel anticonvulsant analogs may therefore represent a possible lead, and additional studies may result in a potential new drug candidate.

Combined Anti-Bacterial Actions of Lincomycin and Freshly Prepared Silver Nanoparticles: Overcoming the Resistance to Antibiotics and Enhancement of the Bioactivity.

Bacterial drug resistance to antibiotics is growing globally at unprecedented levels, and strategies to overcome treatment deficiencies are continuously developing. In our approach, we utilized metal nanoparticles, silver nanoparticles (AgNPs), known for their wide spread and significant anti-bacterial actions, and the high-dose regimen of lincosamide antibiotic, lincomycin, to demonstrate the efficacy of the combined delivery concept in combating the bacterial resistance. The anti-bacterial actions of the AgNPs and the lincomycin as single entities and as part of the combined mixture of the AgNPs-lincomycin showed improved anti-bacterial biological activity in the Bacillus cereus and Proteus mirabilis microorganisms in comparison to the AgNPs and lincomycin alone. The comparison of the anti-biofilm formation tendency, minimum bactericidal concentration (MBC), and minimum inhibitory concentration (MIC) suggested additive effects of the AgNPs and lincomycin combination co-delivery. The AgNPs' MIC at 100 µg/mL and MBC at 100 µg/mL for both Bacillus cereus and Proteus mirabilis, respectively, together with the AgNPs-lincomycin mixture MIC at 100 + 12.5 µg/mL for Bacillus cereus and 50 + 12.5 µg/mL for Proteus mirabilis, confirmed the efficacy of the mixture. The growth curve test showed that the AgNPs required 90 min to kill both bacterial isolates. The freshly prepared and well-characterized AgNPs, important for the antioxidant activity levels of the AgNPs material, showed radical scavenging potential that increased with the increasing concentrations. The DPPH's best activity concentration, 100 µg/mL, which is also the best concentration exhibiting the highest anti-bacterial zone inhibition, was chosen for evaluating the combined effects of the antibiotic, lincomycin, and the AgNPs. Plausible genotoxic effects and the roles of AgNPs were observed through decreased Bla gene expressions in the Bacillus cereus and BlaCTX-M-15 gene expressions in the Proteus mirabilis.

Quality of Life in Patients with Recurrent Oral Squamous Cell Carcinoma: A Study from India.

Background: Locoregional recurrence of oral cancer causes significant morbidity. This study aims at assessing the functional outcomes of patients undergoing treatment for recurrent oral squamous cell carcinoma. Methods: This study was done in a tertiary care center in North India and includes prospective cohort of 179 recurrent oral carcinoma patients, from September 2017 to September 2018. Patients undergoing treatment of recurrent oral carcinoma were assessed for quality-of-life score at baseline before starting treatment and two months after the completion of the treatment. For the assessment, EORTC QLQH&N35 questionnaire was used. Results: Of 179 patients included, 71 (39.66%) patients underwent salvage surgery and 104 patients (58.10%) received palliative chemotherapy. One hundred and thirty patients could complete the "EORTC-QOL-H&N-35" questionnaire on required two occasions. Forty-nine patients died before completing second questionnaire. More than half (55.6%) of patients who underwent salvage surgery had improved quality of life after the procedures. They have little or no pain in oral cavity, improved swallowing, less odynophagia, improvement in neck and shoulder pain, less problems with the external appearance and socialization, and enjoyed better sexual life. In patients receiving palliative chemotherapy, the quality of life declined in majority (88.1%) of the patients. Conclusions: Although salvage surgery is the best modality of treatment for recurrent oral carcinoma, only about one-third of patients qualify for surgery and enjoy improved quality of life following surgery. On the other hand, in majority of the patients receiving palliative chemotherapy, the quality of life worsened with time and treatment.

SPIONs Conjugate Supported Anticancer Drug Doxorubicin's Delivery: Current Status, Challenges, and Prospects.

Considerable efforts have been directed towards development of nano-structured carriers to overcome the limitations of anticancer drug, doxorubicin's, delivery to various cancer sites. The drug's severe toxicity to cardio and hepatic systems, low therapeutic outcomes, inappropriate dose-demands, metastatic and general resistance, together with non-selectivity of the drug have led to the development of superparamagnetic iron oxide nanoparticles (SPIONs)-based drug delivery modules. Nano-scale polymeric co-encapsulation of the drug, doxorubicin, with SPIONs, the SPIONs surface end-groups' cappings with small molecular entities, as well as structural modifications of the SPIONs' surface-located functional end-groups, to attach the doxorubicin, have been achieved through chemical bonding by conjugation and cross-linking of natural and synthetic polymers, attachments of SPIONs made directly to the non-polymeric entities, and attachments made through mediation of molecular-spacer as well as non-spacer mediated attachments of several types of chemical entities, together with the physico-chemical bondings of the moieties, e.g., peptides, proteins, antibodies, antigens, aptamers, glycoproteins, and enzymes, etc. to the SPIONs which are capable of targeting multiple kinds of cancerous sites, have provided stable and functional SPIONs-based nano-carriers suitable for the systemic, and in vitro deliveries, together with being suitable for other biomedical/biotechnical applications. Together with the SPIONs inherent properties, and ability to respond to magnetic resonance, fluorescence-directed, dual-module, and molecular-level tumor imaging; as well as multi-modular cancer cell targeting; magnetic-field-inducible drug-elution capacity, and the SPIONs' magnetometry-led feasibility to reach cancer action sites have made sensing, imaging, and drug and other payloads deliveries to cancerous sites for cancer treatment a viable option. Innovations in the preparation of SPIONs-based delivery modules, as biocompatible carriers; development of delivery route modalities; approaches to enhancing their drug delivery-cum-bioavailability have explicitly established the SPIONs' versatility for oncological theranostics and imaging. The current review outlines the development of various SPIONs-based nano-carriers for targeted doxorubicin delivery to different cancer sites through multiple methods, modalities, and materials, wherein high-potential nano-structured platforms have been conceptualized, developed, and tested for, both, in vivo and in vitro conditions. The current state of the knowledge in this arena have provided definite dose-control, site-specificity, stability, transport feasibility, and effective onsite drug de-loading, however, with certain limitations, and these shortcomings have opened the field for further advancements by identifying the bottlenecks, suggestive and plausible remediation, as well as more clear directions for future development.

Malignant Eccrine Spiroadenoma of Right Temporal region: Reporting of a Rare Case.

Eccrine spiroadenoma arises from adnexal tissue of skin and is usually benign, slow growing and may remain static for decades [1]. Dabska et al. first defined the term malignant eccrine spiroadenoma (MES) in 1972, since then around 100 cases of MES have been found (Alejandra de Andrés Gómez. Malignant eccrine breast spiroadenoma. A case report and literature review [2]). Its very rare kind of tumor can arise either from transformation in benign lesion or can arise de novo. Here we are reporting a case of malignant spiroadenoma arising from transformation of benign lesion, its pathology and treatment.

Guided Needle Aspirations of Intra-Abdominal Masses: Analogy between Liquid-Based and Conventional Smear Preparation Methods.

OBJECTIVE: Image-guided fine needle aspiration cytology with conventional smear (CS) preparation offers onsite cellular adequacy evaluation; however, it still provides false negatives due to faulty smear preparations. Liquid-based cytology (LBC) can be advantageous in these scenarios. Hence, with an aim to investigate utility of LBC in these samples, we carried out the above study with objectives to find diagnostic accuracy of LBC and agreement of LBC with CS methods in guided aspiration samples from intra-abdominal masses. METHODS: A prospective observational study, of 113 patients with clinical or radiological diagnosis of intra-abdominal masses, was carried out. SurePath BD™ was used for LBC smear preparation, and the standard protocol was used for CS preparation. RESULTS: LBC alone was diagnostic in 80.8% of the cases, and CS alone was diagnostic in 71.2% cases (agreement was 83.7%, p = 0.03). Cellular morphology was better preserved in LBC; however, interpretation was easier in CS. CONCLUSION: CS may be complimented with LBC sample collection method to enhance the sensitivity of intra-abdominal FNA.

Radical surgery for de novo gallbladder carcinoma-Single-center analysis of prognostic factors and survival outcomes from an endemic region.

BACKGROUND AND OBJECTIVE: Gallbladder cancer (GBC) is an aggressive malignancy where curative resection is possible in few and survival is poor. There are limited data on outcomes in patients with de novo GBC from endemic regions undergoing surgery for curative intent. We report survival outcomes in this group of patients from a region with high incidence of disease. METHODS: We reviewed the records of all GBC patients (2014-2018) and included those who underwent radical cholecystectomy (RC) for de novo GBC. Univariable and multivariable analyses were performed to identify factors influencing recurrence and survival. RESULTS: A total of 649 patients with GBC were evaluated for surgery and curative intent surgery was attempted in 246 (38%) patients. Of these 246 patients, RC was performed in 115 patients, with histologically confirmed de novo GBC. Locally advanced disease (≥stage IIIB) was present in 52 (45.2%) patients. Median time to recurrence and overall survival (OS) were 31 and 36 months, respectively. Lymph node positivity (p = 0.005) and grade significantly influenced OS on multivariable analysis. CONCLUSION: Satisfactory survival outcomes are possible after RC for de novo GBC. Extended resections performed in high volume centers combined with appropriate adjuvant treatment can offer significant survival benefits, with acceptable morbidity and mortality rates.

Structure-Based Designing, Solvent Less Synthesis of 1,2,3,4-Tetrahydropyrimidine-5-carboxylate Derivatives: A Combined In Vitro and In Silico Screening Approach.

OBJECTIVE: In this study, small molecules possessing tetrahydropyrimidine derivatives have been synthesized having halogenated benzyl derivatives and carboxylate linkage. As previously reported, FDA approved halogenated pyrimidine derivatives prompted us to synthesize novel compounds in order to evaluate their biological potential. METHODOLOGY: Eight pyrimidine derivatives have been synthesized from ethyl acetoacetate, secondary amine, aromatic benzaldehyde by adding catalytic amount of CuCl2·2H2O via solvent less Grindstone multicomponent reagent method. Molecular structure reactivity and virtual screening were performed to check their biological efficacy as an anti-oxidant, anti-cancer and anti-diabetic agent. These studies were supported by in vitro analysis and QSAR studies. RESULTS: After combined experimental and virtual screening 5c, 5g and 5e could serve as lead compounds, having low IC50 and high binding affinity.