Predictors for poor daily weight gain in preterm neonates exposed to different dose regimens of caffeine in ICU- a retrospective cohort study.

BACKGROUND: With a wide therapeutic index, efficacy, ease of use, and other neuroprotective and respiratory benefits, caffeine citrate(CC) is currently the drug of choice for preterm neonates (PTNs). Caffeine-induced excessive energy expenditure, diuresis, natriuresis, and other CC-associated potential side-effects (CC-APSEs) result in lower daily-weight gain (WG) in premature neonates. This study aimed to evaluate the risk factors for daily-WG in neonates exposed to different dose regimens of caffeine in ICU. METHOD: This retrospective cohort study included neonates of ≤ 36weeks gestational age (GA) and received CC-therapy. The same participants were followed for data analysis in two postnatal phases: 15-28 and 29-42 days of life (DOL). Based on daily CC-dose, formed group-I (received; standard-doses = 5 mg/kg/day), group-II (received;>5-7 mg/kg/day), and group-III (received;>7 mg/kg/day). Prenatal and postnatal clinical characteristics, CC-regimen, daily-WG, CC-APSEs, and concomitant risk-factors, including daily-caloric intake, Parenteral-Nutrition duration, steroids, diuretics, and ibuprofen exposure, were analyzed separately for group-II and group-III using group-I as standard. Regression analysis was performed to evaluate the risk factors for daily-WG. RESULTS: Included 314 PTNs. During 15-28 DOL, the mean-daily-WG(MD-WG) was significantly higher in group-I than group-II [19.9 ± 0.70 g/kg/d vs. 17.7 ± 0.52 p = 0.036] and group-III [19.9 ± 0.70 g/kg/d vs. 16.8 ± 0.73 p < 0.001]. During 29-42 DOL the MD-WG of group-I was only significantly higher than group-III [21.7 ± 0.44 g/kg/d vs. 18.3 ± 0.41 g/kg/d p = 0.003] and comparable with group-II. During 15-28 DOL, observed CC-APSEs was significantly higher in group-II and III but during 29-42 DOL it was only significant in group-III. In the adjusted regression analysis for daily-WG during 15-28DOL, with respect to standard-dose, 5-7 mg/kg/day (ß=-1.04; 95%CI:-1.62,-0.93) and > 7-10 mg/kg/day (ß=-1.36; 95%CI:-1.56,-1.02) were associated with a lower daily-WG. However, during 29-42DOL, this association was present only for > 7-10 mg/kg/day (ß=-1.54; 95%CI:-1.66,-1.42). The GA ≤ 27weeks (ß=-1.03 95%CI:-1.24, -0.88) was associated with lower daily-WG only during 15-28DOL. During both periods of therapy, higher cumulative-caffeine dose and presence of culture proven sepsis, tachypnea, hyponatremia, and feeding intolerance were significantly associated with lower daily-WG. Conversely, daily kcal intake was found to be linked with an increase in daily-WG in both periods. CONCLUSION: In this study cohort exposure to higher caffeine daily and cumulative doses is associated with lower postnatal daily-WG in PTNs than standard-daily doses, which may be due to its catabolic effects and CC-APSEs.

Oxidation behavior and atomic structural transition of size-selected coalescence-resistant tantalum nanoclusters.

Herein a series of size-selected TaN(N = 147, 309, 561, 923, 1415, 2057, 6525, 10 000, 20 000) clusters are generated using a gas-phase condensation cluster beam source equipped with a lateral time-of-flight mass-selector. Aberration-corrected scanning transmission electron microscopy (AC-STEM) imaging reveals good thermal stability of TaNclusters in this study. The oxidation-induced amorphization is observed from AC-STEM imaging and further demonstrated through x-ray photoelectron spectroscopy and energy-dispersive spectroscopy. The oxidized Ta predominantly exists in the +5 oxidation state and the maximum spontaneous oxidation depth of the Ta cluster is observed to be 5 nm under prolonged atmosphere exposure. Furthermore, the size-dependent sintering and crystallization processes of oxidized TaNclusters are observed with anin situheating technique, and eventually, ordered structures are restored. As the temperature reaches 1300 °C, a fraction of oxidized Ta309clusters exhibit decahedral and icosahedral structures. However, the five-fold symmetry structures are absent in larger clusters, instead, these clusters exhibit ordered structures resembling those of the crystalline Ta2O5films. Notably, the sintering and crystallization process occurs at temperatures significantly lower than the melting point of Ta and Ta2O5, and the ordered structures resulting from annealing remain well-preserved after six months of exposure to ambient conditions.

Association of Caffeine Daily Dose With Respiratory Outcomes in Preterm Neonates: A Retrospective Cohort Study.

Apnea and poor respiratory drive increase the risk of extubation failure (EF) and prolonged invasive mechanical ventilation (IMV) in preterm neonates (pre-nates) with respiratory distress. Caffeine citrate (CC) is often prescribed for pre-nates in doses of 5-10 mg/kg in 24 h. This study aimed to evaluate the most effective dosage regimen (5 mg/kg/day vs >5-10 mg/kg/day) to prevent apnea and EF with minimal caffeine-associated potential side effects (CC-APSEs) in pre-nates. This one-year retrospective cohort study included all the eligible neonates admitted to NICU and received CC-therapy till 28 days of life (DOL) or discharge. Based on CC-daily dose formed LD-caffeine-group (5 mg/kg/day) and HD-caffeine-group (>5-10 mg/kg/day). Antenatal, prenatal, and postnatal characteristics, CC-regimen, comorbidities, and CC-APSEs were compared between the groups. Predictors of apnea and EF were analyzed through logistic regression. There were 181 and 72 neonates in the LD and HD-caffeine-groups respectively. In HD-caffeine-group daily CC-dose was 7 to 7.5 mg/kg/day in 93% of neonates and >7.5 to 10 mg/kg/day in only 7%. Significantly fewer neonates experienced apnea and EF in the HD-caffeine-group till 28DOL or discharge. This difference was even greater in the subgroup of ≤28 weeks GA (15.6% vs 40.0%; P < .01). In HD-caffeine-group the incidence of severe/moderate-BPD was significantly lower and the frequency of CC-APSEs was higher. Multivariate analysis showed that; the smaller the GA higher the risk of apnea (AOR = 0.510, 95% CI 0.483-0.999) and EF (AOR = 0.787, 95% CI 0.411-0.997). The HD-caffeine was inversely associated with developing apnea (AOR = 0.244, 95% CI 0.053-0.291) and EF (AOR = 0.103, 95% CI 0.098-2.976). IMV-duration before extubation (AOR = 2.229, 95% CI 1.672-2.498) and severe/moderate-BPD (AOR = 2.410, 95%CI 1.104-2.952) had a high risk of EF. Initiating early HD-caffeine may prevent apnea and extubation failure in preterm neonates. Optimization of caffeine initiation time and dosages can be a safe and feasible approach to decrease the burden of neonatal respiratory morbidities.

Fumaria indica (Hausskn.) Pugsley Hydromethanolic Extract: Bioactive Compounds Identification, Hypotensive Mechanism, and Cardioprotective Potential Exploration.

Fumaria indica (Hausskn.) Pugsley (FIP), a member of the Papaveraceae family, has a documented history of use in traditional medicine to treat cardiovascular ailments, particularly hypertension, and has shown substantial therapeutic efficacy among native cultures worldwide. However, the identification of bioactive compounds and the mechanism of hypotensive effect with the cardioprotective potential investigations are yet to be determined. The study aimed to identify bioactive compounds, explore the hypotensive mechanism and cardioprotective potential, and assess the safety of Fumaria indica (Hausskn.) Pugsley hydromethanolic extract (Fip.Cr). LC ESI-MS/MS analysis was performed to identify the bioactive compounds. In vitro experiments were conducted on isolated rat aorta and atria, and an in vivo invasive BP measurement model was used. Acute and subacute toxicities were assessed for 14 and 28 days, respectively. Isoproterenol (ISO) was used to develop the rats' myocardial infarction damage model. The mRNA levels of NLRP3 inflammasome and the abundance level of Firmicutes and Lactobacillus were measured by qRT-PCR. The hypotensive effect of FIP bioactive compounds was also investigated using in silico methods. Fip. Cr LC ESI-MS/MS analysis discovered 33 bioactive compounds, including alkaloids and flavonoids. In isolated rat aorta, Fip.Cr reversed contractions induced by K+ (80 mM), demonstrating a calcium entry-blocking function, and had a vasorelaxant impact on phenylephrine (PE) (1 µM)-induced contractions unaffected by L-NAME, ruling out endothelial NO participation. Fip.Cr caused negative chronotropic and inotropic effects in isolated rat atria unaffected by atropine pretreatment, eliminating cardiac muscarinic receptor involvement. Safety evaluation showed no major adverse effects. In vivo, invasive BP measurement demonstrated a hypotensive effect comparable to verapamil. Fip.Cr protected the rats from ISO-induced MI interventions significantly in biometrical and cardiac serum biochemical indicators and histological examinations by reducing inflammation via inhibiting NLRP3 inflammasome and elevating Firmicutes and Lactobacillus levels. The network pharmacology study revealed that the FIP hypotensive mechanism might involve MMP9, JAK2, HMOX1, NOS2, NOS3, TEK, SERPINE1, CCL2, and VEGFA. The molecular docking study revealed that FIP bioactive compounds docked better with CAC1C_ HUMAN than verapamil. These findings demonstrated that Fip.Cr's hypotensive mechanism may include calcium channel blocker activity. Fip.Cr ameliorated ISO-induced myocardial infarction in rats by attenuating inflammation, which might be via inhibiting NLRP3 inflammasome and may prove beneficial for treating MI.

Facile one-step synthesis of gold nanoparticles using Viscum album and evaluation of their antibacterial potential.

Nanostructure gold nanoparticles (Au NPs) are well-known biological active materials, synthesised under different environment-friendly approaches that has gained significant interest in the field of biomedicine. This study investigated a novel, fast, easy, cost-effective and the eco-friendly method to synthesise Au NPs from mediated Viscum album Linn plant extract, where the plant metabolites act as stabilising and reducing agents. The synthesised Au NPs were analysed by UV/Vis spectroscopy that gave strong signals and a sharp absorption peak at 545nm due to the presence of surface plasmon resonance (SPR) bands. In addition, energy dispersive X-ray spectroscopy (EDX) showed that strong signals of Au NPs appeared at 9.7 and 2.3keV, as the rays of light passed. X-ray diffraction recognised the crystalline material and provided information on the cell unit that the synthesised Au NPs are face-centreed cubic in structure. The diffraction of X-ray spectra showed intense peaks at 38.44°, 44.7°, 44.9° and 77.8°. The mediated V. album plant extracts and synthesised Au NPs were screened against gram-positive and gram-negative (Enterobacter , Salmonella typhi , Escheria coli and Bacillus subtilis ) bacterial strains, confirming their antibacterial potential. Au NPs showed strong antibacterial activity due to its unique steric configuration. Au NPs damaged bacterial cell membrane leading to the leakage of the cytoplasm and death of the cell.

Investigations of plausible pharmacodynamics supporting the antispasmodic, bronchodilator, and antidiarrheal activities of Berberis lycium Royle. Via in silico, in vitro, and in vivo studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Berberis lycium Royle, a member of the Berberidaceae family, is a high-value medicinal plant with a documented history of usage in traditional medicine and has demonstrated significant therapeutic results among local populations throughout the globe. It is used traditionally in many parts of Pakistan to treat diarrhea, abdominal spasms, coughs, and chest problems. AIM OF THE STUDY: To investigate the antispasmodic, bronchodilator, and antidiarrheal effects of B. lycium and its possible underlying mechanisms through in silico, in vitro, and in vivo studies. MATERIALS AND METHODS: LC ESI-MS/MS analysis was used to identify bioactive components within the hydromethanolic extract of B. lycium. In silico studies, including network pharmacology and molecular docking, were utilized to investigate the antispasmodic and bronchodilator properties of the extract's bioactive components. In vitro pharmacological studies were conducted using isolated rabbit jejunum, trachea, urinary bladder, and rat ileum preparations. In vivo antidiarrheal activities were conducted in mice, including castor oil-induced diarrhea, intestinal transit, and castor oil-induced enteropooling. RESULTS: The LC ESI-MS/MS analysis of the hydromethanolic extract of B. lycium identified 38 bioactive compounds. Network pharmacology study demonstrated that the mechanism of BLR for the treatment of diarrhea might involve IL1B, TLR4, PIK3R1, TNF, PTPRC, IL2, PIK3CD, and ABCB1, whereas, for respiratory ailments, it may involve PIK3CG, TRPV1, STAT3, ICAM1, ACE, PTGER2, PTGS2, TNF, MMP9, NOS2, IL2, CCR5, HRH1, and VDR. Molecular docking research revealed that chlorogenic acid, epigallocatechin, isorhamnetin, quinic acid, gallic acid, camptothecin, formononetin-7-O-glucoside, velutin, caffeic acid, and (S)-luteanine exhibited a higher docking score than dicyclomine with validated proteins of smooth muscle contractions such as CACB2_HUMAN, ACM3_HUMAN, MYLK_HUMAN, and PLCG1_HUMAN. In vitro investigations demonstrated that Blr.Cr, Blr.EtOAc, and Blr.Aq relaxed spontaneously contracting jejunum preparations; carbachol (1 µM)-induced and K+ (80 mM)-induced jejunum, trachea, and urinary bladder contractions in a concentration-dependent manner, similar to dicyclomine. Moreover, Blr.Cr, Blr.EtOAc, and Blr.Aq exhibited a rightward shift in Ca+2 and carbachol cumulative response curves, similar to dicyclomine, demonstrating the coexistence of antimuscarinic and Ca+2 antagonistic mechanisms due to the presence of alkaloids and flavonoids. In vivo antidiarrheal activities showed that the hydromethanolic extract was significantly effective against castor oil-induced diarrhea and castor oil-induced enteropooling, similar to loperamide, and charcoal meal intestinal transit, similar to atropine, in mice at doses of 50, 100, and 200 mg/kg body weight, which supports its traditional use in diarrhea. CONCLUSION: The dual blocking mechanism of muscarinic receptors and Ca+2 channels behind the smooth muscle relaxing activity reveals the therapeutic relevance of B. lycium in diarrhea, abdominal spasms, coughs, and chest problems.

Automated facial characterization and image retrieval by convolutional neural networks.

Introduction: Developing efficient methods to infer relations among different faces consisting of numerous expressions or on the same face at different times (e.g., disease progression) is an open issue in imaging related research. In this study, we present a novel method for facial feature extraction, characterization, and identification based on classical computer vision coupled with deep learning and, more specifically, convolutional neural networks. Methods: We describe the hybrid face characterization system named FRetrAIval (FRAI), which is a hybrid of the GoogleNet and the AlexNet Neural Network (NN) models. Images analyzed by the FRAI network are preprocessed by computer vision techniques such as the oriented gradient-based algorithm that can extract only the face region from any kind of picture. The Aligned Face dataset (AFD) was used to train and test the FRAI solution for extracting image features. The Labeled Faces in the Wild (LFW) holdout dataset has been used for external validation. Results and discussion: Overall, in comparison to previous techniques, our methodology has shown much better results on k-Nearest Neighbors (KNN) by yielding the maximum precision, recall, F1, and F2 score values (92.00, 92.66, 92.33, and 92.52%, respectively) for AFD and (95.00% for each variable) for LFW dataset, which were used as training and testing datasets. The FRAI model may be potentially used in healthcare and criminology as well as many other applications where it is important to quickly identify face features such as fingerprint for a specific identification target.

Hepatoprotective effect of methanolic extract of Iris florentina L. on paracetamol-induced liver toxicity in rats.

Despite of plethora of research on hepatoprotective potential of medicinal plants, there is still need to discover potential plants with hepatoprotective activity. Iris florentina L. is a medicinal plant with traditional claims but ignored investigation regarding its hepatoprotective effects. The current study is aimed to investigate the hepatoprotective potential of I. florentina L. methanolic extract on paracetamol (PCM)-induced liver injury. The phytochemical and HPLC screening was done which showed the presence of potential constituents including flavonoids and phenols. For investigating the hepatoprotective effect of I. florentina L. methanolic extract, rats were given five different treatments for seven consecutive days. The normal control (group 1) was administered with normal saline, group 2 (Diseased) received paracetamol and group 3 (Standard) was given silymarin as reference drug. In group 4 and 5 (Treated), I. florentina L. methanolic extract (250 and 500mg/kg) were administered. Different serum biomarkers and histopathological studies were performed to assess the recovery caused by PCM in comparison to diseased group. The treatment of I. florentina methanolic extract significantly improve the serum biomarkers and restored the hepatic injury towards normal, indicating the hepatoprotective potential. Thus, we can conclude that I. florentina have significantly reversed the damage caused by paracetamol in hepatotoxic rat model due to their potential phytochemical constituents.

Decision support system for sustainable groundwater management in crystalline hard rocks: implications for sugarcane agriculture, Southern India.

India is the second largest sugarcane-producing nation with water footprints ~ 104 BCM/year of which 80% met from groundwater of deep wells. The large-scale groundwater management practices were found mostly untenable affecting the sugarcane agrarian and associated sectors. We developed a cell-level (2 km × 2 km) decision support system employing the integrated hydro-geophysical investigations in sugarcane agro-watershed (399 km2) beset over granitic aquifer systems of Tattihalla River watershed, Southern India. The refined hydrogeological conceptual model derived from electrical resistivity tomography and groundwater level (head) has been accounted into the numerical modeling. The model was run on transient mode for four stress periods during 2015-2017 and validated with calculated and observed heads. The normalized RMS error 7.57% of the validated model conveys its robustness and estimates groundwater budget at the demarcated 77 cells. The theoretical scenarios for water level projections against the increased groundwater pumping rates of 10%, 25%, and 50% were generated. It showed a declining trend of water level for the projected 10-year period with varied magnitude and vulnerability for drought conditions. The different time periods of water level touching the basement (i.e., dry borewell) infers a distinct hydrogeological property of an individual cell advocating to adapt a cell level management plan. In this article, we explained two cells (nos. 12 and 60) in detail to show the varying characteristic of aquifer against the different pumping rates.

Double Philadelphia Chromosomes- A Rare, Yet an Important Cytogenetic Phenomenon of Prognostic Significance in De Novo Acute Lymphoblastic Leukemia.

Presence of additional copies of Philadelphia chromosome (Ph) is characteristic of chronic myeloid leukemia in blast crisis, very rarely observed in de novo acute lymphoblastic leukemia (ALL). Ph positive (Ph+ve) ALL and CML in lymphoid blast crisis (CML-LBC) are biologically different with divergent clinical course. Double Ph+ve ALL has little data available as to its incidence and prognostic significance. We studied five cases of Ph+ve precursor B-cell ALL having an extra copy of Ph chromosome with regard to their clinical and laboratory features. An extensive review of literature was done on prognostic significance and molecular aspects of double Ph in ALL. The study confirms that double Ph was a rare phenomenon in precursor B-cell ALL. It is observed that molecular basis of double Ph positive ALL is less understood compared to CML in blast crisis. The study highlights fundamental role of cytogenetic and molecular studies in diagnosis and management of these patients. Long-term follow-up studies on a larger group of patients are required to understand the prognostic impact of extra Ph in Ph+ve ALL, which is usually resistant to standard chemotherapeutic regimen and often requiring bone marrow transplantation. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-022-01525-1.

Pre-phase strategy to mitigate first cycle effect in diffuse large B cell lymphoma.

CONTEXT: Treatment-related toxicities in DLBCL (diffuse large B cell lymphoma) patients are higher in the initial phase of treatment (first cycle effect). Implementation of pre-phase treatment before definitive chemotherapy had been shown to alleviate some of these side-effects in a non-randomized study conducted earlier in our institute (Lakshmaiah et. al., Eur J Haematol 100:644-8, 2018). AIMS: This study was aimed at validating the role of pre-phase treatment in newly diagnosed DLBCL patients. SETTINGS AND DESIGN: All newly diagnosed patients with DLBCL above the age of 18 years were evaluated for eligibility and prospectively enrolled. A single-arm prospective study was conducted at the Department of Medical Oncology, in our institute from July 2015 to December 2019. METHODS AND MATERIAL: Patients received vincristine and prednisolone as pre-phase treatment for 7 days after which definitive chemotherapy was instituted on day 1. They were followed up for 30 days post-first cycle chemotherapy. STATISTICAL ANALYSIS USED: Paired Student's t tests and Wilcoxon signed-ranks test were used for comparison of various clinical variables as appropriate. P value of less than 0.05 was considered significant. RESULTS: Among the 180 patients who were included in study, performance status improvement was noted in significant number of patients (p < 0.001). 38.4% achieved an ECOG (Eastern Cooperative Oncology Group) performance status of 0 post-pre-phase therapy. Febrile neutropenia was observed in 12.8% in the present cohort as compared to the historical non-pre-phase cohort (34%). CONCLUSIONS: Pre-phase therapy significantly improves the performance status and diminishes neutropenia rates in DLBCL patients.

A Highly Efficient RF-DC Converter for Energy Harvesting Applications Using a Threshold Voltage Cancellation Scheme.

In this paper, a self-threshold voltage (Vth) compensated Radio Frequency to Direct Current (RF-DC) converter operating at 900 MHz and 2.4 GHz is proposed for RF energy harvesting applications. The threshold voltage of the rectifying devices is compensated by the bias voltage generated by the auxiliary transistors and output DC voltage. The auxiliary transistors compensate the threshold voltage (Vth) of the PMOS rectifying device while the threshold voltage (Vth) of the NMOS rectifying device is compensated by the output DC voltage. The proposed RF-DC converter was implemented in 180 nm Complementary Metal-Oxide Semiconductor (CMOS) technology. The experimental results show that the proposed design achieves better performance at both 900 MHz and 2.4 GHz frequencies in terms of PCE, output voltage, sensitivity, and effective area. The peak power conversion efficiency (PCE) of 38.5% at -12 dBm across a 1 MΩ load for 900 MHz frequency was achieved. Similarly, for 2.4 GHz frequency, the proposed circuit achieves a peak PCE of 26.5% at -6 dBm across a 1 MΩ load. The proposed RF-DC converter circuit shows a sensitivity of -20 dBm across a 1 MΩ load and produces a 1 V output DC voltage.

Hyperglycemia-associated Alzheimer's-like symptoms and other behavioral effects attenuated by Plumeria obtusa L. Extract in alloxan-induced diabetic rats.

Diabetes mellitus is a chronic metabolic complaint with numerous short- and long-term complications that harm a person's physical and psychological health. Plumeria obtusa L. is a traditional medicine used in the treatment of diabetes to reduce complications related to behavior. Plumeria is a genus with antipsychotic activities. The objective of this study was to examine the effects of a methanolic extract of Plumeria obtusa L. in the attenuation of diabetes, on symptoms of Alzheimer disease, and on other associated behavioral aspects. A single dose of alloxan was administered to an experimental group of rats to induce development of diabetes (150 mg/kg, intraperitoneal) and the rats were then administered selected doses of methanolic extract of Plumeria obtusa L. (Po.Cr) or glibenclamide (0.6 mg/kg) for 45 consecutive days. Behavioral effects were evaluated using three validated assays of anxiety-related behavior: the open field test, the light and dark test, and the elevated plus maze. Anti-depressant effects of Plumeria obtusa L. were evaluated using the forced swim test (FST) and memory and learning were assessed using the Morris water maze (MWM) task. Po.Cr was also evaluated for phytochemicals using total phenolic content (TPC), total flavonoid content (TFC), and high-performance liquid chromatography assays, and antioxidant capability was assessed through assays of DPPH radical scavenging, total oxidation capacity, and total reducing capacity. In the alloxan-induced model of diabetes, the administration of Po.Cr and glibenclamide for 45 days produced a marked decrease (p < 0.001) in hyperglycemia compared to control animals. Po.Cr treatment also resulted in improvement in indicators, such as body weight and lipid profile (p < 0.05), as well as restoration of normal levels of alanine transaminase (ALT) (p < 0.001), a biomarker of liver function. Diabetic rats presented more Alzheimer-like symptoms, with greater impairment of memory and learning, and increased anxiety and depression compared to non-diabetic normal rats, whereas treated diabetic rats showed significant improvements in memory and behavioral outcomes. These results demonstrate that Po.Cr reversed alloxan-induced hyperglycemia and ameliorated Alzheimer-related behavioral changes, which supports additional study and assessment of conventional use of the plant to treat diabetes and associated behavioral complications.

Primary mucinous carcinomas of the lung: Clinical characteristics and treatment outcomes.

INTRODUCTION: Invasive mucinous adenocarcinoma (IMA) of the lung is a distinct histologic variant of adenocarcinomas comprising about 2%-10% of lung adenocarcinomas. A large proportion of IMAs carry KRAS mutations and only rarely epidermal growth factor receptor (EGFR) mutations or ALK/ROS translocations; thus, most cases are not amenable for targeted therapy at present. This study was conducted to elicit the unique clinicopathological characteristics of IMA. MATERIALS AND METHODS: Medical records of patients diagnosed with IMA by needle biopsy at Kidwai Cancer Institute, Bangalore, from 2013 to 2018, were retrieved and reviewed. Statistical analysis was performed using SPSS version 23.0 (IBM Corp., Armonk, NY, USA). RESULTS: Four hundred and ninety cases of needle biopsy of the lung were diagonosed at our institute between January 2013 and December 2018. Nine cases (1.8%) were diagnosed as IMA. The median age of presentation was 59 years. Six (66.7%) were current smokers with pack-year > 20. Three (33.3%) of the cases were initially misdiagnosed as pneumonia in view of computed tomography findings. The lung was the most common site of metastasis (77.8%). Serum Carcinoembryonic Antigen (CEA) was elevated in six cases (66.7%). None of the cases had any driver mutations in EGFR gene or ALK and ROS1 translocations. All cases were treated with pemetrexed-carboplatin doublet followed by pemetrexed maintenance till progression. The median progression-free survival (PFS) was 15 months (range: 5-18 months). Docetaxel was given as the second-line chemotherapy in all progressed patients. Best response noted was stable disease, seen in 4 (57.1%) cases. The median PFS for docetaxel was 6 months (range: 3-8 months). The median overall survival was 22 months (range: 9-27 months). Patients with initially raised CEA at progression had a serial rise in serum CEA. CONCLUSIONS: IMA is rarely diagnosed on needle biopsies due to insufficient tissue. They mimic pneumonia on imaging, thus delaying diagnosis. EGFR mutations, ALK, and ROS1 translocations are usually negative making them ineligible for tyrosine kinase inhibitors. Response to chemotherapy is modest.

Socioeconomic and administrative factors associated with treatment delay of esophageal and gastric carcinoma: Prospective study from a tertiary care centre in a developing country.

This study was aimed to analyze the spectrum of time intervals, from the onset of symptoms to the commencement of treatment in esophagogastric cancers. Factors influencing these time delays and correlation between these time points with variables including socioeconomic strata, educational level, histopathology, location of tumor and the initial modality of treatment were assessed. STUDY SETTING AND METHODS: A prospective analysis of patients with esophagogastric cancer presenting to a single tertiary care unit over a period of 12 months was performed. Histopathology other than adenocarcinoma and squamous cell were excluded. RESULTS: 202 patients were enrolled in the study. Most patients presented with advanced disease, i.e. 91.5 % of esophageal and 90 % of gastric malignancies belonged to either stage 3 or stage 4 as per American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system. The median delay from the appearance of the first symptoms to initiation of treatment was 15 weeks (range 4-64). Patient related factors contributed to a significant delay [median of 5 weeks (range 1-24)]. Administrative factors were responsible for median delay of 3 weeks (range 0.5-20). Curative multimodality treatment was administered in 62.5 % of patients. Significant longer delay was influenced by socioeconomic strata, educational level, evaluation by non-specialist (p < 0.05). No relationship was noted between histopathology, location of tumor or initial modality of treatment. CONCLUSIONS: Delays in our setting is much more than that is seen in Western and even some Asian countries. An important component of delay is administrative related factors. These may be intervened at the hospital level compared to other factors which may need long term community oriented approaches.

Follicular lymphoma transforming to DLBCL and reverting back to follicular lymphoma at relapse-a case report.

BACKGROUND: Transformation of low-grade follicular lymphoma to high-grade diffuse large B cell lymphoma (DLBCL) is known. However, the opposite is not commonly reported. In this report, we present a case of follicular lymphoma that underwent transformation to DLBCL. Three years after treatment for histologic transformation, the patient presented again with low-grade follicular lymphoma at the same site which is unusual in the natural history of follicular lymphoma. CASE PRESENTATION: A 50-year-old female patient presented to us with complaints of slowly progressing swelling in the neck on the left side for a duration of 1 year. Past history of the patient revealed a diagnosis of follicular lymphoma in 2004 for which the patient had taken prednisolone and chlorambucil. Details of staging were not available with the patient. After a complete work-up, she was diagnosed as DLBCL, stage IIIE. She was treated with 6 cycles of CHOP regimen. She had very good response to chemotherapy. However, she defaulted and was lost to follow-up. She presented again after 3 years with history of painless progressive swelling in the right side of the neck for the last 1 year. Examination revealed cervical lymph nodes and ascites. This time, a repeat biopsy and immunohistochemistry was suggestive of follicular lymphoma. In view of significant ascites, she was started on chemotherapy with CVP regimen. After 6 cycles, she has good partial response and resolution of ascites. She is currently on follow-up. CONCLUSIONS: We have presented a case of FL that has transformed to DLBCL after 10 years of diagnosis. After HT, she was treated with CHOP chemotherapy and the patient relapsed again after 3 years with follicular lymphoma histology. This case highlights the unique and varied natural history of follicular lymphoma that may be attributed to different subclones of malignant cells that may have arisen from a common progenitor FL cell and differential effect of chemotherapy on these subclones.

The Material Efforts for Quantized Hall Devices Based on Topological Insulators.

A topological insulator (TI) is a kind of novel material hosting a topological band structure and plenty of exotic topological quantum effects. Achieving quantized electrical transport, including the quantum Hall effect (QHE) and the quantum anomalous Hall effect (QAHE), is an important aspect of realizing quantum devices based on TI materials. Intense efforts are made in this field, in which the most essential research is based on the optimization of realistic TI materials. Herein, the TI material development process is reviewed, focusing on the realization of quantized transport. Especially, for QHE, the strategies to increase the surface transport ratio and decrease the threshold magnetic field of QHE are examined. For QAHE, the evolution history of magnetic TIs is introduced, and the recently discovered magnetic TI candidates with intrinsic magnetizations are discussed in detail. Moreover, future research perspectives on these novel topological quantum effects are also evaluated.

Vision-related quality of life: 12-month aflibercept treatment in patients with treatment-resistant neovascular age-related macular degeneration.

PURPOSE: To assess changes in vision-related quality of life (VR-QoL) among patients with treatment-resistant neovascular age-related macular degeneration (nAMD) following intravitreal aflibercept treatment over 48 weeks. METHODS: We conducted a prospective study in which 49 patients with nAMD resistant to anti-vascular endothelial growth factor therapy were switched to intravitreal aflibercept. Patients were treated with three loading doses every 4 weeks followed by injections every 8 weeks, for a total of 48 weeks. Ophthalmic examinations performed at each visit included best-corrected visual acuity (BCVA) and central macular thickness (CMT) measurement. The National Eye Institute Visual Functioning Questionnaire 25 (NEI VFQ-25) was used to assess VR-QoL at baseline and weeks 24 and 48. Changes in NEI VFQ-25 composite and subscale scores were analyzed using paired t tests. The relationship between the change in VR-QoL and changes in BCVA and CMT, and the impact of the better-seeing eye (BSE, defined as the eye reading the greater number of letters at baseline) vs. the worse-seeing eye (WSE, the fellow eye to the BSE) were assessed. RESULTS: Mean NEI VFQ-25 composite scores improved significantly at weeks 24 and 48 compared to baseline (4.5 ± 9.2 and 4.4 ± 11.8, respectively, all p < 0.01). Among subscales, general vision and near and distance activities showed significant improvements at weeks 24 and 48 (all p < 0.05). Improvement in the NEI VFQ-25 composite score was significantly associated with increased BCVA at week 48 (ß coefficient = 0.43, p = 0.029), but not with change in CMT (ß coefficient = -0.007, p = 0.631). There was no association between VR-QoL changes and BSE or WSE. CONCLUSION: Despite previous anti-VEGF treatment in this cohort, overall VR-QoL improved following aflibercept therapy over 48 weeks. This improvement was related to improved vision in treatment eyes regardless of whether they were the BSE or WSE.

Evaluation of Nonperfused Retinal Vessels in Ischemic Retinopathy.

PURPOSE: Retinal ischemia has been traditionally assessed by fluorescein angiography, visualizing perfused vessels. However, this method does not provide any information about nonperfused vessels, and although it is often assumed that vessels in ischemic areas regress, we know little about how nonperfused retinal vessels change over time. Here, we aim to learn more about the long-term fate of nonperfused vessels in the retinal vasculature. METHODS: Optical coherence tomography (OCT) was used to visualize perfusion as well as structural properties of the retinal vasculature in patients suffering from retinal vascular occlusions. In addition, postmortem tissue from a patient with long standing (6 years) central retinal vein occlusion (CRVO) was investigated, using immunohistochemistry on whole-mount retina and paraffin sections to visualize blood vessel components. RESULTS: Comparing OCT angiography with enface OCT images revealed that in ischemic areas of the retina, nonperfused, larger vessels could be detected as hyperreflective structures in enface OCT images. Furthermore, analysis of a postmortem tissue sample from a CRVO patient with a large nonperfused region in the macula, revealed preservation of the basement membrane from all retinal vessels, including nonperfused, acellular vessels of all calibers. CONCLUSIONS: Our data suggests long-term preservation of vascular basement membrane in ischemic retina. This has implications for therapeutic approaches aiming to alleviate retinal ischemia via the regeneration of damaged vessels.

Thromboelastography--does it impact blood component transfusion in pediatric heart surgery?

BACKGROUND: The administration of blood products during pediatric cardiac surgery is common. We sought to determine if thromboelastography (TEG) is a cost-effective tool to reduce blood product transfusion in open pediatric cardiac surgery. MATERIALS AND METHODS: A retrospective case-control study was undertaken for 150 pediatric cardiac patients requiring cardiopulmonary bypass from January 2010-May 2012, in a University-affiliated pediatric hospital. Fifty sequential patients operated on when TEG was used were compared with 100 control patients before TEG availability. Groups were matched 2:1 for age and risk adjustment for congenital heart surgery score. Blood product utilization was compared between groups, as were outcomes metrics such as postoperative complications, length of stay, and hospital costs of transfusions. RESULTS: Demographic variables, risk adjustment for congenital heart surgery score classifications, and cardiopulmonary bypass times were similar between groups. Red cell and plasma transfusion were comparable between groups. TEG patients saw a substantial reduction in the administration of platelet (1 versus 2.2 U; P < 0.0001) and cryoprecipitate (0.7 versus 1.7 U; P < 0.0001) transfusions. A greater than 50% reductions in hospital costs of platelet ($595 versus $1309) and cryoprecipitate ($39 versus $94) transfusions were observed in the TEG group. Mortality, length of stay, ventilator requirements, postoperative bleeding, and thrombotic events were equivalent. CONCLUSIONS: Intraoperative TEG use reduced platelet and cryoprecipitate transfusions without an increase in postoperative complications. TEG is a cost-effective method to direct blood product replacement.