Pyrazole derivatives of pyridine and naphthyridine as proapoptotic agents in cervical and breast cancer cells.

Cancer is one of the leading causes of death worldwide. The increasing prevalence and resistance to chemotherapy is responsible for driving the search of novel molecules to combat this disease. In search of novel compounds with pro-apoptotic potential, pyrazolo-pyridine and pyrazolo-naphthyridine derivatives were investigated against cervical cancer (HeLa) and breast cancer (MCF-7) cells. The anti-proliferative activity was determined through the MTT assay. Potent compounds were then analyzed for their cytotoxic and apoptotic activity through a lactate dehydrogenase assay and fluorescence microscopy after propidium iodide and DAPI staining. Flow cytometry was used to determine cell cycle arrest in treated cells and pro-apoptotic effect was verified through measurement of mitochondrial membrane potential and activation of caspases. Compounds 5j and 5k were found to be most active against HeLa and MCF-7 cells, respectively. G0/G1 cell cycle arrest was observed in treated cancer cells. Morphological features of apoptosis were also confirmed, and an increased oxidative stress indicated the involvement of reactive oxygen species in apoptosis. The compound-DNA interaction studies demonstrated an intercalative mode of binding and the comet assay confirmed the DNA damaging effects. Finally, potent compounds demonstrated a decrease in mitochondrial membrane potential and increased levels of activated caspase-9 and -3/7 confirmed the induction of apoptosis in treated HeLa and MCF-7 cells. The present work concludes that the active compounds 5j and 5k may be used as lead candidates for the development of lead drug molecules against cervical and breast cancer.

Design, Synthesis, and Biological Evaluation of Novel Dihydropyridine and Pyridine Analogs as Potent Human Tissue Nonspecific Alkaline Phosphatase Inhibitors with Anticancer Activity: ROS and DNA Damage-Induced Apoptosis.

Small molecules with nitrogen-containing scaffolds have gained much attention due to their biological importance in the development of new anticancer agents. The present paper reports the synthesis of a library of new dihydropyridine and pyridine analogs with diverse pharmacophores. All compounds were tested against the human tissue nonspecific alkaline phosphatase (h-TNAP) enzyme. Most of the compounds showed excellent enzyme inhibition against h-TNAP, having IC50 values ranging from 0.49 ± 0.025 to 8.8 ± 0.53 µM, which is multi-fold higher than that of the standard inhibitor (levamisole = 22.65 ± 1.60 µM) of the h-TNAP enzyme. Furthermore, an MTT assay was carried out to evaluate cytotoxicity against the HeLa and MCF-7 cancer cell lines. Among the analogs, the most potent dihydropyridine-based compound 4d was selected to investigate pro-apoptotic behavior. The further analysis demonstrated that compound 4d played a significant role in inducing apoptosis through multiple mechanisms, including overproduction of reactive oxygen species, mitochondrial dysfunction, DNA damaging, and arrest of the cell cycle at the G1 phase by inhibiting CDK4/6. The apoptosis-inducing effect of compound 4d was studied through staining agents, microscopic, and flow cytometry techniques. Detailed structure-activity relationship (SAR) and molecular docking studies were carried out to identify the core structural features responsible for inhibiting the enzymatic activity of the h-TNAP enzyme. Moreover, fluorescence emission studies corroborated the binding interaction of compound 4d with DNA through a fluorescence titration experiment.

Oral Antibiotic Bowel Preparation Prior to Urgent Colectomy Reduces Odds of Organ Space Surgical Site Infections: a NSQIP Propensity-Score Matched Study.

BACKGROUND: Preoperative administration of oral antibiotic bowel preparation (OABP) alone has been shown to reduce infectious outcomes in patients undergoing elective colectomy. However, it remains unclear if these benefits extend to the emergency setting. This is a retrospective, propensity-score matched study comparing 30-day perioperative morbidity between those who received OABP alone versus no preparation prior to urgent colectomy. METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program database, adults undergoing urgent colectomy from 2012 to 2019 were included. Those who were clinically obstructed or who received mechanical bowel preparation were excluded. Outcomes of interest included: surgical site infection (SSI), leak, ileus, and major morbidity. RESULTS: Of 24,559 patients meeting inclusion criteria, 878 (3.6%) received OABP prior to urgent colectomy. Prior to matching, those receiving no preparation were more likely to have higher ASA class, diabetes, hypertension, preoperative sepsis, open procedures, and a dirty wound classification. After matching, 1756 patients, remained with 878 in each arm. Preoperative characteristics were balanced on univariate analysis. Postoperatively, patients receiving OABP experienced decreased organ space SSI (11.2% vs. 15.5%, p = 0.009) and ileus (30.3% vs. 35.3%, p = 0.029), with no difference in leak rates (3.3% vs 3.3%, p = 1.000) or NSQIP major morbidity (47.4% vs. 49.9%, p = 0.316). On multivariate logistic regression, including propensity score, the reduction in organ space SSI associated with OABP persisted (OR 0.684, 95% CI 0.516-0.903). CONCLUSION: OABP prior to select urgent colectomies was associated with fewer organ space SSIs and may be considered when feasible.

A comparison of methods to harmonize cortical thickness measurements across scanners and sites.

Results of neuroimaging datasets aggregated from multiple sites may be biased by site-specific profiles in participants' demographic and clinical characteristics, as well as MRI acquisition protocols and scanning platforms. We compared the impact of four different harmonization methods on results obtained from analyses of cortical thickness data: (1) linear mixed-effects model (LME) that models site-specific random intercepts (LMEINT), (2) LME that models both site-specific random intercepts and age-related random slopes (LMEINT+SLP), (3) ComBat, and (4) ComBat with a generalized additive model (ComBat-GAM). Our test case for comparing harmonization methods was cortical thickness data aggregated from 29 sites, which included 1,340 cases with posttraumatic stress disorder (PTSD) (6.2-81.8 years old) and 2,057 trauma-exposed controls without PTSD (6.3-85.2 years old). We found that, compared to the other data harmonization methods, data processed with ComBat-GAM was more sensitive to the detection of significant case-control differences (Χ2(3) = 63.704, p < 0.001) as well as case-control differences in age-related cortical thinning (Χ2(3) = 12.082, p = 0.007). Both ComBat and ComBat-GAM outperformed LME methods in detecting sex differences (Χ2(3) = 9.114, p = 0.028) in regional cortical thickness. ComBat-GAM also led to stronger estimates of age-related declines in cortical thickness (corrected p-values < 0.001), stronger estimates of case-related cortical thickness reduction (corrected p-values < 0.001), weaker estimates of age-related declines in cortical thickness in cases than controls (corrected p-values < 0.001), stronger estimates of cortical thickness reduction in females than males (corrected p-values < 0.001), and stronger estimates of cortical thickness reduction in females relative to males in cases than controls (corrected p-values < 0.001). Our results support the use of ComBat-GAM to minimize confounds and increase statistical power when harmonizing data with non-linear effects, and the use of either ComBat or ComBat-GAM for harmonizing data with linear effects.

Remodeling of the Cortical Structural Connectome in Posttraumatic Stress Disorder: Results From the ENIGMA-PGC Posttraumatic Stress Disorder Consortium.

BACKGROUND: Posttraumatic stress disorder (PTSD) is accompanied by disrupted cortical neuroanatomy. We investigated alteration in covariance of structural networks associated with PTSD in regions that demonstrate the case-control differences in cortical thickness (CT) and surface area (SA). METHODS: Neuroimaging and clinical data were aggregated from 29 research sites in >1300 PTSD cases and >2000 trauma-exposed control subjects (ages 6.2-85.2 years) by the ENIGMA-PGC (Enhancing Neuro Imaging Genetics through Meta Analysis-Psychiatric Genomics Consortium) PTSD working group. Cortical regions in the network were rank ordered by the effect size of PTSD-related cortical differences in CT and SA. The top-n (n = 2-148) regions with the largest effect size for PTSD > non-PTSD formed hypertrophic networks, the largest effect size for PTSD < non-PTSD formed atrophic networks, and the smallest effect size of between-group differences formed stable networks. The mean structural covariance (SC) of a given n-region network was the average of all positive pairwise correlations and was compared with the mean SC of 5000 randomly generated n-region networks. RESULTS: Patients with PTSD, relative to non-PTSD control subjects, exhibited lower mean SC in CT-based and SA-based atrophic networks. Comorbid depression, sex, and age modulated covariance differences of PTSD-related structural networks. CONCLUSIONS: Covariance of structural networks based on CT and cortical SA are affected by PTSD and further modulated by comorbid depression, sex, and age. The SC networks that are perturbed in PTSD comport with converging evidence from resting-state functional connectivity networks and networks affected by inflammatory processes and stress hormones in PTSD.

Development of a formative feedback tool for transanal total mesorectal excision.

INTRODUCTION: Transanal total mesorectal excision (TaTME) is a novel procedure in the treatment of rectal cancer. Current training models for TaTME suggest a period of proctored cases, but no structured feedback tool exists to guide operators during the learning phase. The objective of this study therefore was to develop a formative feedback tool for the critical steps of the transanal portion of TaTME. METHODS: A two-round Delphi study by TaTME experts was conducted to determine the items to be included in the formative feedback tool. Participants rated each step from a prepared list using a Likert scale from 1 (Not relevant) to 5 (Very relevant) with the option to suggest additional steps. Responses to the first round were presented in the second round, where participants rated the revised list of steps. Consensus was defined as > 80% of participants rating the step as 4 or 5 (out of 5). Items were combined when appropriate to avoid redundancy. Rating anchors describing performance (on a 5-point scale) were then developed for each step. The final tool was recirculated and participants rated the finished product on its feasibility and usefulness. RESULTS: Twenty-six TaTME experts were contacted for participation. Fifteen experts (58%) participated in the first round of the study, and eleven (42%) participated in the second round. The majority (14, 93%) had completed fellowship training in colorectal surgery. The first round of the Delphi study contained 34 items, and 32 items met inclusion criteria after the second round. Redundant items were combined into 15 items that comprised the final tool. Out of eight respondents to the feasibility survey, all believed the feedback tool enhances the feedback of learners and would use it for training purposes if available. CONCLUSION: This work describes the development of a novel consensus-based formative feedback tool specific to TaTME.

A Novel Method of Quantifying the Choriocapillaris in Normal and Post-inflammatory Eyes.

OBJECTIVE: To assess the reliability and validity of gray level co-occurrence matrices (GLCM) in the quantification of choriocapillaris and describe GLCM features in normal and eyes with resolved acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and serpiginous choroiditis (SC). METHODS: In this, multicenter, reliability, validity and comparative study; OCTA was performed on eyes with resolved APMPPE and SC and normal individuals. CC texture classification, low flow area measurements and GLCM feature extraction were performed. RESULTS: A total of 13 normal, 8 APMPPE and 15 SC eyes were analyzed. All GLCM parameters demonstrated an excellent reliability. GLCM parameters were differently distributed across the three groups. Decision-tree based on the random forest predictive model provided an overall accuracy of 86% in classifying the three groups using GLCM features. CONCLUSION: These data demonstrated an excellent reliability and validity of GLCM features in quantifying the choriocapillaris in healthy and diseased eyes.

Deep eutectic solvent mediated synthesis of 3,4-dihydropyrimidin-2(1H)-ones and evaluation of biological activities targeting neurodegenerative disorders.

Substitution of hazardous and often harmful organic solvents with "green" and "sustainable" alternative reaction media is always desirous. Ionic liquids (IL) have emerged as valuable and versatile liquids that can replace most organic solvents in a variety of syntheses. However, recently new types of low melting mixtures termed as Deep Eutectic Solvents (DES) have been utilized in organic syntheses. DES are non-volatile in nature, have sufficient thermal stability, and also have the ability to be recycled and reused. Hence DES have been used as alternative reaction media to perform different organic reactions. The availability of green, inexpensive and easy to handle alternative solvents for organic synthesis is still scarce, hence our interest in DES mediated syntheses. Herein we have investigated Biginelli reaction in different DES for the synthesis of 3,4-dihydropyrimidin-2(1H)-ones. Monoamine oxidases and cholinesterases are important drug targets for the treatment of various neurological disorders such as Alzheimer's disease, Parkinson's disease, depression and anxiety. The compounds synthesized herein were evaluated for their inhibitory potential against these enzymes. Some of the compounds were found to be highly potent and selective inhibitors. Compounds 1 h and 1c were the most active monoamine oxidase A (MAO A) (IC50 = 0.31 ± 0.11 µM) and monoamine oxidase B (MAO B) (IC50 = 0.34 ± 0.04 µM) inhibitors respectively. All compounds were selective AChE inhibitors and did not inhibit BChE (<29% inhibition). Compound 1 k (IC50 = 0.13 ± 0.09 µM) was the most active AChE inhibitor.

Formulation and assessment of controlled release tablets of famotidine by using eudragit RL 100 polymer.

Controlled release in drug release kinetics denotes reproducibility and predictability, implying that drug release from delivery devices follows a kinetically predictable and repeatable rate profile from dose to dose. In the current study controlled release tablets of famotidine were prepared by direct compression technique using Eudragit RL 100 polymer. Four different formulations of controlled release tablets of famotidine as (F1, F2, F3 and F4) were prepared by adding different drug to polymer ratio. The pre compression and the post compression of the formulation, characteristics were compared. All results obtained were within the specified standard limits. FTIR studies showed that both the drug and the polymer were compatible. In vitro dissolution study were conducted by Method II (Paddle Method) in phosphate buffer (pH 7.4), at 100rpm. Power law kinetic model was applied for drug release mechanism. The difference similarity of the dissolution profile was determined. The formulation F1 and F2 were released 97 and 96 % in 24 hours and other formulations F3 and F4 were released subsequently 93% and 90% in 24 hours. The results showed that incorporation of Eudragit RL 100 in the formulation of controlled release tablets prolong the drug release rates for 24 hours. The release mechanism was Non-Fickian diffusion mechanism. It was deducted from the current study that the Eudragit RL 100 can be efficiently incorporated in the formulation of controlled release dosage forms with predictable kinetics.

Antiproliferative and Pro-Apoptotic Effects of Thiazolo[3,2-b][1,2,4]triazoles in Breast and Cervical Cancer Cells.

BACKGROUND AND OBJECTIVES: Cancer is one of the leading causes of death in the world affecting millions of people. The commercially available anticancer drugs lack the selectivity and show several undue side effects during the biologically targeted therapy, thus calling for the exploration of wider chemical space to furnish new structural leads with promising anticancer potential. In this endeavor, we synthesized a series of coumarinyl thiazolotriazoles with diverse functional group tolerance and will be tested for their anticancer properties against cancer cell lines (HeLa and MCF-7) and a normal cell line (BHK-21). MATERIALS AND METHODS: To overcome such complications, in the current study, we evaluated the cytotoxic effects of coumarinyl thiazolotriazole hybrids on human breast adenocarcinoma (MCF-7), cervical adenocarcinoma (HeLa) cells and normal cells i.e., Baby Hamster Kidney cells (BHK-21) using MTT (dimethyl-2-thiazolyl- 2,5-diphenyl-2H-tetrazolium bromide) assay. DNA binding studies of compound 6c was performed on Herring- Sperm DNA (HS-DNA) and docking studies were also carried out. The mechanistic studies were performed on potent compounds by fluorescent microscopic studies, release of Lactate Dehydrogenase (LDH) and mitochondrial membrane potential, activation of caspase-9 and -3 and flow cytometric analysis. RESULTS: As revealed by MTT assay, compounds 6m and 6c were identified as the most potent derivatives among the tested series with IC50 values of 5.64 and 29.1 µM against HeLa and MCF cells, respectively as compared to cisplatin which gave IC50 values of 11.3 and 6.20 µM, respectively. DNA binding studies of compound 6c showed the binding of compound in DNA with Gibbs free energy of ‒17 KJ/mol and docking studies validated the DNA binding studies. Fluorescent microscopic studies using 4',6-diamidino-2-phenylindole (DAPI) and Propidium Iodide (PI) staining confirmed the occurrence of apoptosis in HeLa cells treated with the most active compound 6m. Moreover, compounds 6m and 6c also triggered the release of Lactate Dehydrogenase (LDH) in treated HeLa and MCF-7 cells while a luminescence assay displayed a remarkable increase in the activity of caspase-9 and -3. Moreover, flow cytometric results revealed that compound 6m caused G0 /G1 arrest in the treated HeLa cells. CONCLUSION: Our results suggested that the compound possesses chemotherapeutic properties against breast cancer and cervical adenocarcinoma cells, thus warranting further research to test the anticancer efficacy of this compound at clinical level.

New triorganotin(iv) compounds with aromatic carboxylate ligands: synthesis and evaluation of the pro-apoptotic mechanism.

Three new organotin(iv) carboxylate compounds were synthesized and structurally characterized by elemental analysis and FT-IR and multinuclear NMR (1H, 13C, 119Sn) spectroscopy. Single X-ray crystallography reveals that compound C2 has a monoclinic crystal system with space group P21/c having distorted bipyramidal geometry defined by C3SnO2. The synthesized compounds were screened for drug-DNA interactions via UV-Vis spectroscopy and cyclic voltammetry showing good activity with high binding constants. Theoretical investigations also support the reactivity of the compounds as depicted from natural bond orbital (NBO) analysis using Gaussian 09. Synthesized compounds were initially evaluated on two cancer (HeLa and MCF-7) cell lines and cytotoxicity to normal cells was evaluated using a non-cancerous (BHK-21) cell line. All the compounds were found to be active, with IC50 values less than that of the standard drug i.e. cisplatin. The cytotoxic effect of the most potent compound C2 was confirmed by LDH cytotoxicity assay and fluorescence imaging after PI staining. Apoptotic features in compound C2 treated cancer cells were visualized after DAPI staining while regulation of apoptosis was observed by reactive oxygen species generation, binding of C2 with DNA, a change in mitochondrial membrane potential and expression of activated caspase-9 and caspase-3 in cancer cells. Results are indicative of activation of the intrinsic pathway of apoptosis in C2 treated cancer cells.

Anticancer evaluation of a manganese complex on HeLa and MCF-7 cancer cells: design, deterministic solvothermal synthesis approach, Hirshfeld analysis, DNA binding, intracellular reactive oxygen species production, electrochemical characterization and density functional theory.

Herein, a deterministic solvothermal strategy was employed to synthesize an efficient anticancer agent 'cis-dichlorobis(1,10-phenanthroline)manganese(II)' (Mn(phen)2Cl2). A single-crystal X-ray diffraction analysis revealed that Mn(phen)2Cl2 crystallizes in a triclinic system with the space group P-1. Cyclic voltammetric studies of Mn(phen)2Cl2 indicated that the electrode process occurs only due to complex formation and has a diffusion-controlled mechanism. Density functional theory estimations showed that the Mn(phen)2Cl2 is quite stable and exists in sextet spin state (five unpaired electrons) as the most stable form and hence, Mn(phen)2Cl2 is a high spin complex. Mn(phen)2Cl2 demonstrated significant anticancer potential against HeLa and MCF-7 cancer cells and less toxic behaviour towards normal BHK-21 cells. Fluorescence imaging confirmed that the production of reactive oxygen species (ROS) in HeLa cells by Mn(phen)2Cl2 induces oxidized fluorescence of dichlorofluorescein which emitted fluorescence at 530 nm after excitation at 488 nm. The microscopic investigation of apoptotic effect of Mn(phen)2Cl2 using propidium iodide and 4',6-diamidino-2-phenylindole staining indicated that nuclear condensation, cell detachment and shrinkage occur after treatment with IC50 values of Mn(phen)2Cl2. Furthermore, an assessment of caspase-9 and caspase-3 activity after exposure to Mn(phen)2Cl2 in HeLa cells indicated that at IC50 values of Mn(phen)2Cl2, 1.5 fold and 4.8 fold increase in caspase-9 and caspase-3 activity, respectively, occurs. The measurement of mitochondrial membrane potential of a cationic dye (JC-1) showed a decrease in mitochondrial membrane potential in both HeLa and MCF-7 cells depicting that compound might have adopted intrinsic pathway of apoptosis. Ability of Mn(phen)2Cl2 to interact with HS-DNA demonstrates hyperchromicity with slight blue shift from 269 nm to 265 nm showing a non-covalent interaction with Gibbs free energy of ΔG = -14.62 kJ/mol. Communicated by Ramaswamy H. Sarma.

In Vitro Anticancer Effects of Stilbene Derivatives: Mechanistic Studies on HeLa and MCF-7 Cells.

BACKGROUND AND OBJECTIVE: The growing prevalence of cancer and the resulting chemoresistance exert a huge burden on healthcare systems and impose a great challenge to public health around the world. In efforts to develop new chemotherapeutic agents for cancer treatment, a class of heterocyclic compounds i.e. triazine-based molecules were investigated as anticancer agents. MATERIALS AND METHODS: New triazine hybrids of stilbene were synthesized and evaluated as anticancer agents for cervical (HeLa) and breast (MCF-7) carcinoma cells. The compound (7e), sodium (E)-6,6'-(ethene-1,2- diyl)bis(3-((4-chloro-6-((3-luorophenyl)amino)-1,3,5-triazin-2-yl)amino)benzenesulfonate) was found to be most potent among synthesized derivatives and was explored further for detailed mechanistic studies. RESULTS: In a set comprised of twelve derivatives, compound 7e, sodium (E)-6,6'-(ethene-1,2-diyl)bis(3-((4- chloro-6-((3-luorophenyl)amino)-1,3,5-triazin-2-yl)amino)benzenesulfonate) was found most potent inhibitor for HeLa and MCF-7 cells. DISCUSSION: The present study has revealed that compound 7e may activate mitochondrial pathway of apoptosis in HeLa and MCF-7 cells which was assessed by DNA binding studies, estimation of the release of Lactate Dehydrogenase (LDH), fluorescence imaging, production of Reactive Oxygen Species (ROS) in cancer cells, analysis of cell cycle by flow cytometry, change in Mitochondrial Membrane Potential (MMP) and activation of caspase-9 and caspase-3. CONCLUSION: Compound 7e may serve as a lead in designing new anticancer compounds based on stilbene scaffold.

New Hybrid Scaffolds Based on Carbazole-Chalcones as Potent Anticancer Agents.

BACKGROUND AND OBJECTIVES: Despite various technological advances for the treatment of cancer, the identification of new chemical entities with potent anticancer effects remain an indispensable requirement of the time due to multi-drug resistance exhibited by previously developed anticancer drugs. Particularly, the hybrid drugs incorporating two individual bioactive pharmacophores present medicinally important structural leads, thus improving the pharmacodynamic profile of the drug molecules. The antiproliferative and pro-apoptotic activity of the carbazole-chalcone hybrids on human breast and cervical cancer cells will be examined. MATERIALS AND METHODS: To overcome such complications, in the current study, we evaluated the cytotoxic effects of carbazole-chalcone hybrids on human breast adenocarcinoma (MCF-7), cervical adenocarcinoma (HeLa) cells and normal cells, i.e., Baby Hamster Kidney cells (BHK-21) using MTT (dimethyl-2-thiazolyl-2,5- diphenyl-2H-tetrazolium bromide) assay. The mechanistic studies were performed on potent compound 4g by fluorescent microscopic studies, release of Lactate Dehydrogenase (LDH) and mitochondrial membrane potential, activation of caspase-9 and -3 and flow cytometric analysis. RESULTS: As revealed by MTT assay, compound 4g was identified as the most potent derivative among the tested series with IC50 values of 5.64 and 29.15µM against HeLa and MCF-7 cells, respectively. The results were compared with cisplatin. Fluorescent microscopic studies using 4',6-diamidino-2-phenylindole (DAPI) and Propidium Iodide (PI) staining confirmed the occurrence of apoptosis in HeLa cells treated with the most active compound 4g. Moreover, compound 4g also triggered the release of Lactate Dehydrogenase (LDH) in treated HeLa and MCF-7 cells while a fluorescence assay displayed a remarkable increase in the activity of caspase-9 and -3. Moreover, flow cytometric results revealed that compound 4g caused G0/G1 arrest in the treated HeLa cells. CONCLUSION: Our results demonstrated that the compound 4g possesses chemotherapeutic properties against breast cancer and cervical adenocarcinoma cells, thus warranting further research to test the anticancer potential of this compound at preclinical and clinical level.

Acute Respiratory Events and Dosimetry of Total Body Irradiation Patients Using In Vivo Lung Dose Monitoring and Custom Lung Block Adaptation.

PURPOSE: Most myeloablative regimens before stem cell transplant involved total body irradiation (TBI). Pulmonary complications from TBI contribute to treatment-related mortality and toxicity. We report the rate of acute respiratory complications after TBI at our institution. In an exploratory analysis, we investigated differences in dosimetry between patients who did and did not experience respiratory complications. METHODS AND MATERIALS: In this single institution retrospective study, 49 patients received TBI from 2016 to 2018 and had dosimetry data available for analysis. Patients were prescribed 1200 cGy to be delivered over 6 fractions. Lung doses were limited using custom lung blocks. Clinical lung complications (eg, coughing and shortness of breath) were reviewed for the hospitalization period during transplant, at 4 months after transplant, and at 1 year after transplant. Supplemental oxygen use during the hospitalization period was also reported. Median anterior-posterior diameter at the umbilicus, body mass index, and lung doses were compared between patients with and without respiratory complications using a Mann-Whitney U test. RESULTS: During the hospitalization period, 14% (n = 7) of patients used supplemental oxygen administered by nasal canula and 16% (n = 8) experienced respiratory symptoms. At the 4-month follow-up, 16% (n = 8) of patients had documented respiratory symptoms. Respiratory symptoms were grade 1 to 2 except for one grade 3 attributed to infection during the hospitalization period and another grade 3 due to infection during the 4-month follow-up. At 1-year post-TBI, 4% (n = 2) of patients reported grade 1 to 2 chronic cough. Patients with respiratory complications at the 4-month follow-up had a larger umbilical anterior-posterior diameter (31.5 cm vs 26.5 cm, P = .01) and body mass index (34.5 kg/m2 vs 29.7 kg/m2, P = .02) than patients without respiratory complication. Respiratory complications were not associated with higher lung doses. CONCLUSIONS: There was no respiratory-related mortality using the individualized planning technique described here. Acute and chronic respiratory complications were minor, with the most significant intervention requiring antibiotics for respiratory infection.

Readmission for Treatment Failure After Nonoperative Management of Acute Diverticulitis: A Nationwide Readmissions Database Analysis.

BACKGROUND: The true incidence of, and risk factors for, readmission for treatment failure after nonoperative management of acute diverticulitis remain poorly understood. OBJECTIVE: The purpose of this study was to describe the incidence and risk factors for readmission for treatment failure after nonoperative management of acute diverticulitis using a large national database. DESIGN: This was a retrospective cohort study. SETTINGS: A representative sample of admissions and discharges from hospitals in the United States captured in the National Readmissions Database were included. PATIENTS: Adult patients (age ≥18 y) admitted with a primary diagnostic of colonic diverticulitis between 2010 and 2015 and who were managed nonoperatively and discharged from hospital alive were included. INTERVENTIONS: Study intervention included nonoperative management, consisting of medical therapy with or without percutaneous drainage. MAIN OUTCOME MEASURES: Readmission for treatment failure (defined as a nonelective readmission for diverticulitis within 90 d of discharge), complicated treatment failure (defined as a treatment failure with complicated diverticulitis), and time-to-treatment failure were measured. RESULTS: In total, 201,384 patients were included. The overall incidence of readmission for treatment failure was 6.6%. Treatment failure was significantly higher among patients with an index episode of acute complicated diverticulitis compared with acute uncomplicated diverticulitis (12.5% vs 5.7%; p < 0.001). The median time-to-readmission for treatment failure was 21.0 days (range, 20.4-21.6 d), and 85% of all readmissions occurred within 60 days of discharge. On multiple logistic regression, factors independently associated with readmission for treatment failure were an index admission of complicated diverticulitis (OR = 2.06 (95% CI, 1.97-2.16)), disposition on discharge (against medical advice: OR = 1.92 (95% CI, 1.66-2.20); home health care arrangements: OR = 1.24 (95% CI, 1.16-1.33)), and immunosuppression (OR = 1.42 (95% CI, 1.28-1.57)), among others. Risk factors for a complicated treatment failure were also described, after an index episode of complicated and uncomplicated diverticulitis. LIMITATIONS: The study was limited by residual confounding from missing covariates and its observational study design. CONCLUSIONS: The incidence of readmission for treatment failure after an episode of diverticulitis managed nonoperatively is 6.6%, and an index episode of complicated diverticulitis is the strongest risk factor for treatment failure. See Video Abstract at http://links.lww.com/DCR/B92. REINGRESO POR FRACASO DEL TRATAMIENTO DESPUÉS DEL TRATAMIENTO NO QUIRÚRGICO DE LA DIVERTICULITIS AGUDA: UN ANÁLISIS DE LA BASE DE DATOS DE REINGRESOS A NIVEL NACIONAL: La verdadera incidencia y los factores de riesgo para el reingreso por fracaso del tratamiento después de manejo no quirúrgico de la diverticulitis aguda siguen siendo mal definidos.Definir la incidencia y los factores de riesgo de reingreso por fracaso del tratamiento no quirúrgico de la diverticulitis aguda utilizando una base de datos nacional.Estudio de cohorte retrospectivo.Una muestra representativa de ingresos y egresos de hospitales en los Estados Unidos capturados en la base de datos nacional de reingresos hospitalarios.Pacientes adultos (≥18 años) ingresados con un diagnóstico primario de diverticulitis colónica entre 2010-2015, y que fueron tratados de forma no operativa y dados de alta del hospital vivos.Manejo no quirúrgico, que consiste en terapia médica con o sin drenaje percutáneo.Reingreso por fracaso del tratamiento (definido como un reingreso no electivo por diverticulitis dentro de los 90 días despues de ser dados de alta), fracaso del tratamiento complicado (definido como un fracaso del tratamiento con diverticulitis complicada) y el tiempo hasta el tratamiento en casos fracasaados.201.384 pacientes incluidos en total. La incidencia global de reingreso por fracaso del tratamiento fue del 6,6%. El fracaso del tratamiento fue significativamente mayor entre los pacientes con un episodio índice de diverticulitis aguda complicada en comparación con la diverticulitis aguda no complicada (12.5% vs. 5.7%, p <0.001). La mediana del tiempo hasta el reingreso por fracaso del tratamiento fue de 21.0 (20.4 - 21.6) días, y el 85% de todos los reingresos ocurrieron dentro de los 60 días posteriores a ser dados de alta. En la regresión logística múltiple, los factores asociados independientemente con el reingreso por fracaso del tratamiento fueron un índice de admisión de diverticulitis complicada (OR 2.06, IC 95% 1.97-2.16), disposición (de alta en contra del consejo médico: OR 1.92, IC 95% 1.66-2.2; atención médica domiciliaria: OR 1.24, IC 95% 1.16-1.33) e inmunosupresión (OR 1.42, IC 95% 1.28-1.57), entre otros. Los factores de riesgo para un fracaso del tratamiento complicado también se describieron, respectivamente, después de un episodio índice de diverticulitis complicada y no complicada.Covariables faltantes y diseño de estudio observacional.La incidencia de reingreso por fracaso del tratamiento después de un episodio de diverticulitis manejado de forma no operativa es del 6,6%, y un episodio índice de diverticulitis complicada es el factor de riesgo más fuerte para el fracaso del tratamiento. Consulte Video Resumen en http://links.lww.com/DCR/B92. (Traducción-Dr. Adrian E. Ortega).

Synthesis, characterization, and anticancer activity of Schiff bases.

Five Schiff bases, 2-((3-chlorophenylimino)methyl)-5-(diethylamino)phenol (L1), 2-((2,4-dichlorophenylimino)methyl)-5-(diethylamino)phenol (L2), 5-(diethylamino)-2-((3,5-dimethylphenylimino)methyl)phenol (L3), 2-((2-chloro-4-methylphenylimino)methyl)-5-(diethylamino)phenol (L4), and 5-(diethylamino)-2-((2,6-diethylphenylimino)methyl)phenol (L5) were synthesized and characterized by elemental analysis, FT-IR, 1H and 13C NMR spectroscopy. Three of the compounds (L1, L2, and L4) were analyzed by single crystal X-ray diffraction: L1 and L2 crystallized in orthorhombic P212121 and Pca21 space group, respectively, while L4 crystallized in monoclinic P21/c space group. Theoretical investigations were performed for all the synthesized compounds to evaluate the structural details. Drug-DNA interaction studies results from UV-Vis spectroscopy and electrochemistry complement that the compounds bind to DNA through electrostatic interactions. The cytotoxicity of the synthesized compounds was studied against cancer cell lines (HeLa and MCF-7) and a normal cell line (BHK-21) by means of an MTT assay compared to carboplatin, featuring IC50 values in the micromolar range. The pro-apoptotic mechanism for the active compound L5 was evaluated by fluorescence microscopy, cell cycle analysis, caspase-9 and -3 activity, reactive oxygen species production, and DNA binding studies that further strengthen the results of that L5 is a potent drug against cancer.Communicated by Ramaswamy H. Sarma.

Are right-sided colectomies for neoplastic disease at increased risk of primary postoperative ileus compared to left-sided colectomies? A coarsened exact matched analysis.

INTRODUCTION: The objective of this study was to determine whether right-sided colectomies (RC) were associated with a higher incidence of primary postoperative ileus (pPOI) compared to left-sided colectomies (LC). METHODS: Patients who underwent elective colectomy for neoplastic disease between 2012 and 2016 were identified using the American College of Surgeons National Surgical Quality Improvement Program database. RC and LC were defined as having an ileocolic or colocolic/colorectal anastomosis, respectively. Coarsened Exact Matching (CEM) was used to balance the two groups (1:1) on important confounders. The association between type of colectomy and pPOI, defined as POI in the absence of intra-abdominal sepsis, was then assessed in a multiple logistic regression analysis of the matched data. RESULTS: Of 40,636 patients who underwent a colectomy for neoplastic disease, 15,231 underwent a RC and 25,405 a LC. After CEM, 12,949 matched patients remained in each group, and all important confounders were well balanced. The incidence of pPOI was higher in the RC group (11.5% vs. 8.8%, p < 0.001). On multiple logistic regression, RC was associated with a 35% higher odds of developing pPOI compared to LC (OR 1.35, 95% CI 1.25-1.47). RC was also associated with increased risk for NSQIP-defined major morbidity (OR 1.10, 95% CI 1.01-1.20), 30-day readmission (OR 1.16, 95% CI 1.06-1.27), and increased length of stay (ß = 0.16 days, 95% CI 0.11-0.22). CONCLUSION: pPOI is more common after RC than LC. Future research should aim at better understanding the pathophysiology behind this increased risk and identifying interventions to mitigate pPOI in this population.

Textural Properties of Choriocapillaris on OCTA in Healed Inflammatory Choriocapillaropathies.

BACKGROUND AND OBJECTIVE: To evaluate the flow characteristics and textural properties of choriocapillaris (CC) on optical coherence tomography angiography in eyes with resolved inflammatory choriocapillaropathies and Vogt-Koyanagi-Harada (VKH) disease. PATIENTS AND METHODS: A cohort of eyes with healed acute posterior multifocal placoid pigment epitheliopathy (APMPPE), serpiginous choroiditis (SC), and VKH disease were included. A 3 mm × 3 mm OCT angiogram of CC was acquired and graded for flow characteristics and textural properties. RESULTS: This study included 16 patients. Texture was heterogeneous in all eyes in the SC and VKH groups, and in four eyes (40%) in the APMPPE group. Most of the eyes with VKH disease had severe low flow, whereas most of the SC and APMPPE eyes demonstrated mild low flow. Heal duration had a strong negative correlation with severity of CC low flow and a weak, statistically nonsignificant correlation with texture heterogeneity. CONCLUSION: Despite the resolution of active inflammation, partial CC hypoperfusion and texture disruptions persist for longer durations and may resolve in a time dependent manner. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:566-572.].

Eco-friendly green synthesis of silver nanoparticles and their potential applications as antioxidant and anticancer agents.

Eco-friendly green synthesis of nanoparticles using medicinal plants gained immense importance due to its potential therapeutic uses. In the current study, silver nanoparticles (AgNPs) were synthesized using water extract of Jurinea dolomiaea leaf and root at room temperature. MTT assay was used to study anticancer potential of AgNPs against cervical cancer cell line (HeLa), breast cancer cell lines (MCF-7), and mouse embryonic fibroblast (NIH-3 T3) cell line for toxicity evaluation. The antioxidant potential was evaluated using stable DPPH radicals. In addition, the apoptotic nuclear changes prompted by AgNPs in more susceptible HeLa cells were observed using fluorescence microscope through DAPI and PI staining. Physiochemical properties of biosynthesized AgNPs were characterized using various techniques. AgNPs were formed in very short time and UV-vis spectra showed characteristic absorption peak of AgNPs. SEM and TEM showed spherical shape of AgNPs and XRD revealed their crystalline nature. EDX analysis revealed high percentage of silver in green synthesized AgNPs. FTIR analysis indicated involvement of secondary metabolites in fabrication of AgNPs. In vitro cytotoxic and antioxidant study revealed that herb and biosynthesized AgNPs exhibited significant dose-dependent and time-dependent anticancer and antioxidant potential. Furthermore, study on normal cell line and microscopic analysis of apoptosis revealed that AgNPs exhibited good safety profile as compared to cisplatin and induces significant apoptosis effect. Based on the current findings, it is strongly believe that use of J. dolomiaea offers large scale production of biocompatible AgNPs that can be used as alternative anticancer agents against cancer cell lines tested.