An assessment of a sleep aid and sleep promotion practices in hospitalized medical patients.

BACKGROUND: Half of patients admitted to medicine units report sleep disruption, which increases the risk of sleep deprivation. Non-pharmacological interventions are the first step to improving sleep. However, utilization of sleep aids continues to be prevalent. Limited data are available on sleep aid prescribing practices across transitions of care. OBJECTIVES: The aim of this study was to describe the current practices for assessing sleep and prescribing pharmacologic agents to promote sleep in the adult medicine population. METHODS: This study was designed as a single-center, retrospective, observational cohort study of all patients discharged by the general medicine teams over a 3-month period (September 2019- November 2019). Prior to admission, inpatient and discharge prescriptions for sleep aids were recorded, and documentation of sleep assessments and non-pharmacological interventions were evaluated. RESULTS: Of 754 patients included, 211 (28%) were prescribed a sleep aid while inpatient. During hospitalization, 124 (16%) patients had at least one documented sleep assessment, and only 22 (3%) were ordered the institutional non-pharmacological sleep promotion order set. The most prescribed sleep aid in inpatients was melatonin (50%), as well as prior to admission (35%) and at discharge (25%). Overall, the relative reduction in sleep aid prescriptions between admission and discharge was 67%. CONCLUSION: Inpatient sleep aid prescribing is common in medical patients. Despite this, sleep assessments and the standard of care of non-pharmacological interventions are rarely utilized. Future efforts should focus on implementation of strategies to make sleep assessments and non-pharmacological sleep promotion routine and consistent in the inpatient setting.

Tensor-RT-Based Transfer Learning Model for Lung Cancer Classification.

Cancer is a leading cause of death across the globe, in which lung cancer constitutes the maximum mortality rate. Early diagnosis through computed tomography scan imaging helps to identify the stages of lung cancer. Several deep learning-based classification methods have been employed for developing automatic systems for the diagnosis and detection of computed tomography scan lung slices. However, the diagnosis based on nodule detection is a challenging task as it requires manual annotation of nodule regions. Also, these computer-aided systems have yet not achieved the desired performance in real-time lung cancer classification. In the present paper, a high-speed real-time transfer learning-based framework is proposed for the classification of computed tomography lung cancer slices into benign and malignant. The proposed framework comprises of three modules: (i) pre-processing and segmentation of lung images using K-means clustering based on cosine distance and morphological operations; (ii) tuning and regularization of the proposed model named as weighted VGG deep network (WVDN); (iii) model inference in Nvidia tensor-RT during post-processing for the deployment in real-time applications. In this study, two pre-trained CNN models were experimented and compared with the proposed model. All the models have been trained on 19,419 computed tomography scan lung slices, which were obtained from the publicly available Lung Image Database Consortium and Image Database Resource Initiative dataset. The proposed model achieved the best classification metric, an accuracy of 0.932, precision, recall, an F1 score of 0.93, and Cohen's kappa score of 0.85. A statistical evaluation has also been performed on the classification parameters and achieved a p-value <0.0001 for the proposed model. The quantitative and statistical results validate the improved performance of the proposed model as compared to state-of-the-art methods. The proposed framework is based on complete computed tomography slices rather than the marked annotations and may help in improving clinical diagnosis.

Systematic Next Generation Sequencing is feasible in clinical practice and identifies opportunities for targeted therapy in women with uterine cancer: Results from a prospective cohort study.

BACKGROUND: Both incidence and mortality of uterine cancer are on the rise and mortality is higher for African American women. The aim of our study was to evaluate how Next Generation Sequencing (NGS) may facilitate identification of and intervention for treatment disparities when integrated into clinical workflows. RESULTS: Our cohort included 159 uterine cancer patients with recurrent/progressive and newly diagnosed advanced stage and/or high-risk histology. The most common tumor histological subtypes included EEC (n = 67), SEC (n = 34), UCS (n = 20), and mixed (n = 14). Black patients were most likely to present with aggressive histology: (SEC, 34.0%) and carcinosarcoma (UCS, 14.0%). The four most common mutations across all subtypes were TP53, PIK3CA, PTEN, and ARID1A. There was racial disparity between Black versus non-Black patients who were initiated on targeted therapy (28.2% vs. 38.2%, respectively) and clinical trial (15% vs. 22.6%, respectively). Compared to non-Black patients, Black patients had a significantly higher percentage TP53 mutations (p < 0.05) and a significantly lower percentage ARID1A mutations (p < 0.05). CONCLUSIONS: NGS for uterine malignancies provides actionable information for targetable mutations and/or clinical trial enrollment in most patients; further investigation is necessary to identify potentially modifiable factors contributing to current disparities that may improve targeted therapy uptake and clinical trial participation.

Epidemiology of Intensive Care Unit-acquired Infections in a Tertiary Care Hospital of North India.

BACKGROUND: The majority of nosocomial infections in the hospital setting are found in intensive care units (ICUs). The present study was undertaken to determine the incidence, risk factors, causative microorganisms, and outcome of various ICU-acquired infections. MATERIALS AND METHODS: The patients admitted to the ICU of a teaching hospital in North India were prospectively studied. Detailed history, clinical examination, acute physiology and chronic health evaluation score II, simplified acute physiology score II, sequential organ failure assessment score, and baseline investigations were recorded. Patients were assessed daily till 14th day for nosocomial infection as per Centers for Disease Control and Prevention (CDC) guidelines and were followed till death or discharge. Incidence, risk factors, and outcome parameters were calculated using Student t-test, Chi-square test, and stepwise multivariate logistic regression model. RESULTS: The overall incidence rate of ICU infections was 27.9%. The most common ICU-acquired infection was ventilator-associated pneumonia followed by catheter-related bloodstream infection and catheter-associated urinary tract infection. Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae were implicated in most of the infections. ICU length of stay (LOS) >7 days, neurological dysfunction, endotracheal intubation, ischemic heart disease, and use of antacids/H2 blockers were significantly associated with ICU-acquired infections. The mortality rate was 32.8 and 28.8% in patients with and without ICU infections, respectively (p = 0.531). The ICU LOS (19.23 ± 12.79 days) was significantly higher in the ICU infections group (p <0.001). CONCLUSION: Ventilator-associated pneumonia was the most common nosocomial infection in our study. Gram-negative microorganisms were the predominant causative agents for various ICU-acquired infections. Mortality was not found to be affected but ICU LOS was significantly prolonged as a consequence of the development of ICU-acquired infection. HOW TO CITE THIS ARTICLE: Kumar A, Chaudhry D, Goel N, Tanwar S. Epidemiology of Intensive Care Unit-acquired Infections in a Tertiary Care Hospital of North India. Indian J Crit Care Med 2021;25(12):1427-1433.

Prevalence of Hoarding in an Adult Inpatient Population and Its Association With Axis I Diagnoses.

OBJECTIVE: Hoarding behavior is not limited to obsessive-compulsive disorder (OCD) alone. With the objective of highlighting the association between hoarding behavior and common psychiatric disorders, we explored its occurrence in psychiatric inpatients and co-occurrence with Axis I diagnoses. METHODS: In this prospective cohort study, we enrolled adult psychiatric inpatients by simple random sampling at an urban, community-based, academic medical center. Patients were screened for hoarding using the validated Hoarding Rating Scale-Interview, and those meeting criteria for clinically significant hoarding were assessed for Axis I disorders. RESULTS: Clinically significant hoarding was observed in 33% of the 200 acute psychiatry patients admitted to the study. Mood disorders were positively associated with hoarding (p = 0.033), whereas psychotic spectrum disorders had a weaker association with it (p = 0.015). CONCLUSION: This study indicates a need for clinicians to be mindful that hoarding manifests in many forms of mental illness and is not limited to OCD alone.

From Information to Simulation: Improving Competency in ECT Training Using High-Fidelity Simulation.

OBJECTIVE: This study was intended to develop a new educational model that supplements ECT didactics with simulation-based procedural training and to evaluate the learning gains conferred by such a curriculum. METHODS: Two types of curricula were evaluated for educational efficacy in this prospective randomized controlled trial. Psychiatry residents (n = 35) completed surveys to ascertain their baseline experience, knowledge, and proficiency with the ECT procedure. They were then block-randomized to receive either a didactic ECT curriculum (non-SIM) or one augmented by simulation training (SIM). Three months post-completion of the two types of instruction, all residents were re-administered the surveys and a procedural post-assessment. RESULTS: The median number of ECTs performed prior to the study was similar between the two groups (SIM group = 3, non-SIM group = 4.) The SIM group showed significant improvement on pre- and post- survey theoretical knowledge scores: 51% (95% CI = 41 to 61%) and 69% (95% CI = 64 to 74%), respectively, p = .02; this difference was not significant in the non-SIM group, p = .2. Improvement between pre- and post- proficiency scores were seen in the SIM group: 22% (95% CI = 13 to 32%) and 51% (95% CI = 53 to 59%), p < .001 while the effect was less pronounced in the non-SIM group. Inter-rater agreement for the proficiency assessment was excellent: k, = .9. CONCLUSIONS: Residents showed significant improvement in knowledge, comfort, and skills following ECT simulation training. With the proposed curriculum, residents would receive comprehensive education not only in the theory behind ECT but also in procedural skills. This curriculum can be modeled in other programs that do not have extensive ECT facilities.

A multi-label dataset and its evaluation for automated scoring system for cleanliness assessment in video capsule endoscopy.

An automated scoring system for cleanliness assessment during video capsule endoscopy (VCE) is presently lacking. The present study focused on developing an approach to automatically assess the cleanliness in VCE frames as per the latest scoring i.e., Korea-Canada (KODA). Initially, an easy-to-use mobile application called artificial intelligence-KODA (AI-KODA) score was developed to collect a multi-label image dataset of twenty-eight patient capsule videos. Three readers (gastroenterology fellows), who had been trained in reading VCE, rated this dataset in a duplicate manner. The labels were saved automatically in real-time. Inter-rater and intra-rater reliability were checked. The developed dataset was then randomly split into train:validate:test ratio of 70:20:10 and 60:20:20. It was followed by a comprehensive benchmarking and evaluation of three multi-label classification tasks using ten machine learning and two deep learning algorithms. Reliability estimation was found to be overall good among the three readers. Overall, random forest classifier achieved the best evaluation metrics, followed by Adaboost, KNeighbours, and Gaussian naive bayes in the machine learning-based classification tasks. Deep learning algorithms outperformed the machine learning-based classification tasks for only VM labels. Thorough analysis indicates that the proposed approach has the potential to save time in cleanliness assessment and is user-friendly for research and clinical use. Further research is required for the improvement of intra-rater reliability of KODA, and the development of automated multi-task classification in this field.

Longitudinal Trends in In-Patient Antibiotic Consumption According to the WHO Access, Watch, Reserve (AWaRe) Antibiotic Groups and Cost: An Analysis of Data at a National Antimicrobial Consumption Network (NAC-NET) Site in North India over 7 Years (2017-2023).

(1) Background: Antibiotic surveillance data are crucial to map out strategies to promote their optimal use at hospital and community levels. We conducted a comprehensive analysis of longitudinal trends in antibiotic consumption over 7 years at a core "National Antimicrobial Consumption Network" site in North India. (2) Methods: In-patient antibiotic consumption data (2017-2023) were obtained from the hospital's central drug store and organised as follows: defined daily dose per 100 bed-days; antibiotic consumption as per the WHO access, watch and reserve classification; trends in overall and different antibiotic classes' consumption; paediatric formulations of antibiotics; and hospital's annual expenditure on antibiotics. (3) Results: During the 7-year study period, no significant trend could be observed in the overall antibiotic consumption (average annual percent change, AAPC: 9.22; 95% CI: -16.46, 34.9) and cost (AAPC: 13.55; -13.2, 40.3). There was a higher proportion of the consumption of antibiotics in the "reserve" group from 2021 onwards compared to previous years, but the overall trend over 7 years was not significant (AAPC: 319.75; -137.6, 777.1). Antibiotic combinations, classified under the WHO "not recommended" category, comprised a significant proportion of antibiotics consumed. A remarkably increased consumption of azithromycin and doxycycline was recorded during 2020 and 2021, coinciding with the COVID-19 pandemic. (4) Conclusions: Some recommendations to optimise antibiotic use are promoting the use of narrow spectrum "access" group agents; linking antimicrobial resistance and consumption data to formulate effective therapeutic and prophylactic antibiotic use guidelines; and the adoption of restrictive antibiotic policy.

Syntheses, structural, computational, and thermal analysis of acid-base complexes of picric acid with N-heterocyclic bases.

Four new acid-base complexes using picric acid [(OH)(NO2)3C6H2] (PA) and N-heterocyclic bases (1,10-phenanthroline (phen)/2,2';6',2"-terpyridine (terpy)/hexamethylenetetramine (hmta)/2,4,6-tri(2-pyridyl)-1,3,5-triazine (tptz)) were prepared and characterized by elemental analysis, IR, NMR and X-ray crystallography. Crystal structures provide detailed information of the noncovalent interactions present in different complexes. The optimized structures of the complexes were calculated in terms of the density functional theory. The thermolysis of these complexes was investigated by TG-DSC and ignition delay measurements. The model-free isoconversional and model-fitting kinetic approaches have been applied to isothermal TG data for kinetics investigation of thermal decomposition of these complexes.

Cytomorphological findings of Trichophyton rubrum infection in an elderly hypertensive woman.

Trichophyton is a dermatophytic fungi causing superficial skin infections which affects outermost layer of the epidermis, stratum corneum, and mainly involves feet, groin, scalp, and nails. Invasion into the dermis occurs mainly in immunocompromised patients. A 75-year-old hypertensive female presented with a nodular swelling on the dorsum of right foot for 1 month. The swelling was 1.0 × 1.0 cm and gradually progressive in nature. FNAC revealed many thin filamentous branching and fungal hyphae along with foreign body granulomas and suppurative acute inflammation. The swelling was excised and sent for histopathological examination which confirmed the above findings. Periodic Acid Schiff stain showed fungal hyphae in both cytology smear as well as histopathology section. On fungal culture, microconidia with septate hyphae suggestive of Trichophyton rubrum was seen. Trichophytons mainly affect immunocompromised and diabetic patients, however, may present as nodular lesions without any history of superficial dermatophytosis as seen in the present case. The characteristic cytological picture helped to clinch the diagnosis in this case and facilitated further management.

Gastritis as an immunotherapy-related toxicity in the treatment of endometrial cancer: A case report.

Gastritis related to immunotherapy use is a less commonly reported adverse effect. With increasing use of immunotherapy agents in the management of patients with endometrial cancer, even rare adverse effects are being seen more frequently in gynecologic oncology practice. A 66-year-old with recurrent mismatch repair deficient endometrial cancer was treated with single-agent pembrolizumab. She initially appeared to tolerate treatment well; however after 16 months of therapy she began to develop nausea, vomiting, and abdominal pain that resulted in 30-pound weight loss. Pembrolizumab was held out of concern for immunotherapy related toxicity. She underwent evaluation with gastroenterology including esophagogastroduodenoscopy (EGD) with biopsy that demonstrated severe lymphocytic gastritis. She was treated with IV methylprednisolone with improvement in symptoms over three days. She was then transitioned to oral prednisone at 60 mg daily with weekly taper by 10 mg, with a proton pump inhibitor (PPI) and carafate until resolution of symptoms. She subsequently had a follow up EGD with biopsy, which demonstrated resolving gastritis. She is presently doing well off of steroids with stable disease noted on her last scan after cessation of pembrolizumab.

WHO-Point Prevalence Survey of Antibiotic Use Among Inpatients at a Core National Antimicrobial Consumption Network Site in North India: Findings and Implications.

Data on Point Prevalence Surveys (PPSs) in India are limited yet. We report findings of a PPS conducted in a core "National Antimicrobial Consumption Network site" under National Centre for Disease Control - WHO project "Point prevalence survey of antimicrobial consumption at healthcare facilities." A cross-sectional survey was conducted as per the "WHO methodology for PPS on antibiotic use in hospitals" in a tertiary care hospital in India in December 2021. Data were collected using predesigned and pretested questionnaire in separate hospital, ward, and patient forms. Eight hundred two inpatients (excluding ICUs) were covered out of whom 299 (37.3%) were on antibiotics with 11.7% receiving 3 or more antibiotics. Surgical prophylaxis (SP) (42.5%) and community acquired infections (32.8%) were the most common indications for antibiotic use. Of the patients, 92.5% received SP for more than 24 hrs. Most commonly prescribed antibiotics were penicillins with beta-lactamase inhibitors (22.3%). Of the total antibiotic prescriptions, 81.5% were from WHO essential medicines list and 12% from "not recommended" WHO AWaRe classification. Of the antibiotic prescriptions, 84.6% were parenteral. Few prescriptions complied with standard treatment guidelines (1.9%), documented indication for antibiotic use (11.6%), and stop/review date (4.4%) in notes. Double anaerobic cover accounted for 6.8% of the total prescriptions. Some identified areas for improvement were: formulation of hospital antibiotic guidelines, promoting culture of sending cultures, improvement in surgical antibiotic prophylaxis, decreasing use of antibiotic combinations and double anaerobic cover, fostering IV to oral switch of antibiotics, and ensuring effective communication among health care workers by documenting adequate information in medical notes.

Synthesis of anionic hypervalent cyclic selenenate esters: relevance to the hypervalent intermediates in nucleophilic substitution reactions at the selenium(II) center.

The synthesis of a diaryl diselenide that contains 2,6-dicarboxylic acid groups, 2,2'-diselanediylbis(5-tert-butylisophthalic acid) (10), is described. Diselenide 10 undergoes intramolecular cyclization in methanol to form a cyclic selenenate ester, 5-tert-butyl-3-oxo-3H-benzo[c][1,2]oxaselenole-7-carboxylic acid (11). The cyclization reaction proceeds more rapidly in the presence of organic bases, such as pyridine, adenine, and 4,4'-bipyridine, to form pyridinium 5-tert-butyl-3-oxo-3H-benzo[c][1,2]oxaselenole-7-carboxylate (14), adeninium 5-tert-butyl-3-oxo-3H-benzo[c][1,2]oxaselenole-7-carboxylate (15), and 4,4'-bipyridiniumbis(5-tert-butyl-3-oxo-3H-benzo[c][1,2]oxaselenole-7-carboxylate) (16), respectively. However, 2,2'-diselanediyldibenzoic acid (22) does not undergo cyclization under similar conditions. Structural studies on cyclic selenenate esters 14-16 revealed that the Se···O (COO(-)) secondary distances (2.170, 2.075, and 2.176 Å) were significantly shorter than the corresponding Se···O distances (2.465, 2.472, and 2.435 Å) observed for the selenenate esters stabilized by the neutral donors (CHO, COOH, and COOEt). (1)H, (13)C, and (77)Se NMR spectroscopy of compounds 11 and 14-16 reveal that the aryl protons of compound 11 and the organic cations of compounds 14-16 exchange between the two carboxylate groups via a hypercoordinate intermediate. The corresponding hypercoordinate intermediate (14b, pyridinium selenuranide) for compound 14 was detected at low temperatures using (77)Se NMR spectroscopy. The presumed hypercoordinate intermediates in the carboxylate-exchange reactions at the selenium(II) center for a set of model reactions were optimized using DFT-B3LYP/6-311+g(d) calculations and their structural features compared with the X-ray structure of anionic selenenate esters 14-16.

Selenadiazolopyridine: a synthon for supramolecular assembly and complexes with metallophilic interactions.

The synthesis and characterization of the complexes of Cu(I), Ag(I), Cu(II), and Co(II) ions with 1,2,5-selenadiazolopyridine (psd) is reported. The following complexes have been prepared: [Cu(2)(psd)(3)(CH(3)CN)(2)](2+)2(PF(6)(-)); [(CuCl)(2)(psd)(3)]; [Cu(2)(psd)(6)](2+)2(ClO(4))(-); [Ag(2)(psd)(2)](2+)2(NO(3))(-); [Ag(2)(psd)(2)](2+)2(CF(3)COO)(-); [Cu(psd)(2)(H(2)O)(3)](2+)2(ClO(4))(-)·(psd)(2); [Cu(psd)(4)(H(2)O)](2+)2(ClO(4))(-)·(CHCl(3)); [Cu(psd)(2)(H(2)O)(3)](2+)2(NO(3))(-)·(H(2)O)·(psd)(2), and [Co(psd)(2)(H(2)O)(4)](2+)2(ClO(4))(-)·(psd)(2). The electronic structure of ligand psd, in particular the bond order of Se-N bonds, has been probed by X-ray diffraction, (77)Se NMR, and computational studies. A detailed analysis of the crystal structures of the ligand and the complexes revealed interesting supramolecular assembly. The assembly was further facilitated by the presence of neutral ligands for some complexes (Cu(II) and Co(II)). The molecular structure of the ligand showed that it was present as a dimer in the solid state where the monomers were linked by strong secondary bonding Se···N interactions. The crystal structures of Cu(I) and Ag(I) complexes revealed the dinuclear nature with characteristic metallophilic interactions [M···M] (M = Cu, Ag), while the Cu(II) and Co(II) complexes were mononuclear. The presence of M···M interactions has been further probed by Atoms in Molecules (AIM) calculations. The paramagnetic Cu(II) and Co(II) complexes have been characterized by UV-vis, ESI spectroscopy, and room temperature magnetic measurements.

Heterocyclic Compounds: Importance in Anticancer Drug Discovery.

Cancer, a crucial global health problem, is characterized by abnormal cell division and uncontrolled growth. According to WHO, cancer is the second leading cause of global deaths and accounted for approximately 9.6 million deaths or one in six deaths in 2018. The National Cancer Registry Programme Report 2020, released by the ICMRIndia, estimated that there would be 13,90,000 cases of cancer in India in 2020 and that this number is likely to rise to 15,70,000 by 2025. In spite of several anti-cancer drugs, cancer cannot be cured completely, especially at late stages. In the current era, almost every person is suffering from some kind of disease. Thus, it is the necessity of time to develop novel, potent bioactive molecules. Many researchers are working on the development of new lead molecules or finding a new biological target for the betterment of human beings. However, heterocycles are constantly being used for the discovery of new lead molecules. Many of the clinically approved drugs contain the heterocyclic core as these molecules show exhilarating pharmaceutical properties, including anti-cancer agents such as methotrexate, vinblastine, vincristine, daunorubicin, 5-fluorouracil, doxorubicin, etc. Thus, heterocyclic compounds provide a fascinating research area for the design and development of anti-cancer drug(s). Herein, we focused on the natural as well as synthetic anti-cancer heterocyclic compounds. Furthermore, efforts have been made toward the mechanism of action of selected heterocyclic anti-cancer compounds.

Fever of Unknown Origin and Hepatitis as the Initial Presentation of Anti-MDA-5 Positive Dermatomyositis: A Case Report.

Petersdorf and Beeson first defined fever of unknown origin (FUO) in 1961, and subsequently, over the next 60 years, the definition of FUO has changed considerably. In the western world, non-infectious inflammatory diseases are the most common cause of FUO; however, in developing countries, infections remain the leading cause of FUO. Dermatomyositis (DM) is an autoimmune inflammatory disease of unknown aetiology which mainly affects skin and muscles. Anti-melanoma differentiation-associated protein 5 (MDA-5) positive DM generally presents with classical cutaneous manifestations, early interstitial lung disease, and patients generally do not have clinical features of muscle involvement. We present a case of a 39-year-old male who presented with FUO and hepatitis and was diagnosed as clinically amyopathic DM after two weeks of admission. Subsequently, he was found to have a high titre of Anti-MDA-5 antibody. This is the first case of Anti-MDA-5 positive DM presenting as FUO and hepatitis with a favourable outcome to the best of our knowledge.

Extrapolation of hydroxytyrosol and its analogues as potential anti-inflammatory agents.

Discovery of potential lead molecule is a challenging, and complex process which require lots of money, patience, and manpower. Human beings are using natural products, predominantly secondary metabolites, for this purpose since ancient time and they are still working on them as a potent source for drug discovery due to their wide structural diversity. Phenolic phytochemicals such as hydroxytyrosol and tyrosol are natural antioxidant and involved in many biological disease cure. Herein, we have carried out the quantum chemical calculations for conformational analysis, geometry optimization and computation of electronic as well as optical properties of hydroxytyrosol and its analogues (1a-1k) in terms of density functional theory by using Gaussian 09 program suite. The eventual charge transfer within the molecules has been confirmed by the analysis of frontier molecular orbitals. The molecular docking studies of 1a-1k with cyclooxygenase-2 showed the noticeable binding affinity as compared to other nonsteroidal anti-inflammatory drugs viz. aspirin, naproxen and celecoxib. Computation of pharmacokinetics and pharmacological properties confirmed the lead/drug like potential of these screened molecules. Furthermore, the molecular dynamics simulation of best three docked ligands (1f, 1h and 1k)-receptor complex and their binding free energy calculations reveals that these molecules bind in the catalytic cavity of cyclooxygenase-2 and found stable during the 100 ns of simulation. Communicated by Ramaswamy H. Sarma.

Superior Mesenteric Artery Stenosis Due to Disseminated Tuberculosis in a Pediatric Patient.

Disseminated tuberculosis (TB) associated with mesenteric arteritis has not been established in children. We present the case of an 8-year-old woman who presented with TB and superior mesenteric artery stenosis. Although rare, large vessel involvement from Takayasu arteritis can occur in TB. Evaluation for mesenteric vessel involvement should be considered in pediatric patients presenting with widely disseminated TB and abdominal pain.

Strategies in Overcoming Homologous Recombination Proficiency and PARP Inhibitor Resistance.

Ovarian cancer is the second most common gynecologic malignancy in the United States and the most common cause of gynecologic cancer-related death. The majority of ovarian cancers ultimately recur despite excellent response rates to upfront platinum- and taxane-based chemotherapy. Maintenance therapy after frontline treatment has emerged in recent years as an effective tool for extending the platinum-free interval of these patients. Maintenance therapy with PARP inhibitors (PARPis), in particular, has become part of standard of care in the upfront setting and in patients with platinum-sensitive disease. Homologous recombination deficient (HRD) tumors have a nonfunctioning homologous recombination repair (HRR) pathway and respond well to PARPis, which takes advantage of synthetic lethality by concomitantly impairing DNA repair mechanisms. Conversely, patients with a functioning HRR pathway, that is, HR-proficient tumors, can still elicit benefit from PARPi, but the efficacy is not as remarkable as what is seen in HRD tumors. PARPis are ineffective in some patients due to HR proficiency, which is either inherent to the tumor or potentially acquired as a method of therapeutic resistance. This review seeks to outline current strategies employed by clinicians and scientists to overcome PARPi resistance-either acquired or inherent to the tumor.