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Aim: There are two types of intestinal volvulus: midgut (MGV) and segmental (SV). Patients with different types of intestinal volvulus are often included in the same case series, which may affect the perception of how severe "intestinal volvuli" are. We aimed to compare both types of intestinal volvulus., Methods: This is a retrospective observational study including all patients with MGV and SV up to 28 days of life admitted to a tertiary hospital in Spain over a 20-year-period (1999-2019). A comparison between groups and a logistic regression model for mortality were done., Results: We identified 32 patients: 23 MGV and 9 SV. Malrotation was exclusive of MGV. Prenatal diagnosis, cystic fibrosis, and intestinal resection were significantly more frequent in SV. Surgery was performed at a significantly lower age in SV. The mortality observed in acute MGV with intestinal compromise (41.7%) is four times higher than the mortality of SV (11.1%). The overall mortality of all MGV patients (21.7%) is almost twice that of SV. Mortality was best predicted by the presence of hemodynamic instability (OR 27.5 95% CI 2.50-302.17; p = 0.007)., Conclusion: SV and MGV have a different clinical presentation. Hemodynamic instability is the major risk factor for death., (© 2021 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Background: Transmission of SARS-CoV-2 in health care facilities poses a challenge against pandemic control. Health care workers (HCWs) have frequent and high-risk interactions with COVID-19 patients. We undertook a cost-effectiveness analysis to determine optimal testing strategies for screening HCWs to inform strategic decision-making in health care settings., Methods: We modeled the number of new infections, quality-adjusted life years lost, and net costs related to six testing strategies including no test. We applied our model to four strata of HCWs, defined by the presence and timing of symptoms. We conducted sensitivity analyses to account for uncertainty in inputs., Results: When screening recently symptomatic HCWs, conducting only a PCR test is preferable; it saves costs and improves health outcomes in the first week post-symptom onset, and costs $83,000 per quality-adjusted life year gained in the second week post-symptom onset. When screening HCWs in the late clinical disease stage, none of the testing approaches is cost-effective and thus no testing is preferable, yielding $11 and 0.003 new infections per 10 HCWs. For screening asymptomatic HCWs, antigen testing is preferable to PCR testing due to its lower cost., Conclusions: Both PCR and antigen testing are beneficial strategies to identify infected HCWs and reduce transmission of SARS-CoV-2 in health care settings. IgG tests' value depends on test timing and immunity characteristics, however it is not cost-effective in a low prevalence setting. As the context of the pandemic evolves, our study provides insight to health-care decision makers to keep the health care workforce safe and transmissions low., (© 2022. The Author(s).)

Introduction: Therapeutic hypothermia (TH) improves survival and neurological prognosis in hypoxic-ischemic encephalopathic (HIE) babies, being better the sooner TH is implemented. HIE babies are born more frequently in a non-cooling centre and need to be referred., Methods: Prospective-observational study (April 18 2018 - November 19 2019). Newborns (≥34 weeks of gestational age (GA) and >1800 g) with moderate/severe HIE on non-servocontrolled therapeutic hypothermia by the two neonatal transport teams in Catalonia., Results: 51 newborns. The median stabilisation and transport time were 68 min (p25-75, 45-85 min) and 30 min (p25-75, 15-45 min), respectively. The mean age at arrival at the receiving unit was 4 h and 18 min (SD 96.6). The incubator was set off in 43 (84%), iced-packs 11 (21.5%) and both (11, 21.5%). Target temperature was reached in 19 (37.3%) babies. There were no differences in the overcooling in relation to the measures applied. The transport duration was not related with temperature stabilisation or target temperature reachiness., Conclusions: Rectal temperature monitorisation is compulsory for the stabilisation and the application of non-servocontrolled hypothermia during transport. There is still time for improving in the administration of this treatment during transport. Servo-controlled hypothermia would be a better alternative to improve the management of HIE babies., (Copyright © 2021 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.)

Nondisclosure of prognosis of advanced cancer is commonly practiced in some Asian cultures including India; but research is limited. To describe experiences of Indian oncologists in discussing cancer prognosis with people with cancer and their caregivers, with a focus on barriers and facilitators of prognostic discussions. Thirty oncologists practicing in South India, Hyderabad participated in semi-structured interviews; and analyzed using Interpretative Phenomenological Analysis. Barriers included system-level, patient-level, and physician-level challenges as obstructions to open and honest interactions around cancer prognosis. Most of the barriers focused on communication-related challenges. Lack of communication skills training for providers coupled with over-reliance on use of euphemisms, hesitation in communicating with "weak" patient, and struggles to establish healthcare proxy described communication-related barriers. The study also described factors including family involvement in cancer care and empathic communication as facilitators of honest and open communication about prognosis. In particular, rapport building and getting to know the patient, use of empathic communication, engaging in gradual and individualized disclosure, and balancing hope with honesty were communication-related facilitators that aid open communication with patients with cancer and their caregivers about prognosis and plan of care. Results provide implications for development of communication skills trainings for oncology physicians in India. Adapting, delivering, and evaluating existing communication skills training programs, particularly around discussions of prognosis and goals of care is a requisite step for providing patient-centered and supportive care to patients with cancer and their caregiving families., (© Society of Behavioral Medicine 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The opioid epidemic in the United States has generated a pressing need to enhance access to medications for opioid use disorder (MOUD). This program description illustrates a quality-improvement effort to extend MOUD to primary care and general mental health clinics within the US Department of Veterans Affairs (VA) Connecticut Healthcare system (VACHS), and to examine barriers and facilitators to implementation of MOUD in target clinics., Observations: As part of the national VA Stepped Care for Opioid Use Disorder Train the Trainer (SCOUTT) initiative to improve MOUD access, a VACHS team identified and resolved barriers to MOUD in target clinics. Key interventions were to obtain leadership support, increase waivered prescribers, and develop processes and tools to enhance prescribing. New initiatives included quarterly educational sessions, templated progress notes, and instant messaging for addiction specialist electronic consultations. MOUD receipt and prescriber characteristics were evaluated before and 1 year after implementation. There was a 4% increase in eligible patients receiving MOUD, from 552 (44%) to 582 (48%) ( P = .04). The number of waivered prescribers increased from 67 to 131, and the number of buprenorphine prescribers increased from 35 to 52 over a 6-month span, and the percentage of health care practitioners capable of prescribing within the electronic health record increased from 75% to 89% ( P = .01)., Conclusions: An interdisciplinary team approach to identifying and overcoming barriers to MOUD target clinics expands access. Key interventions include interdisciplinary leadership engagement, proactive education and incentivization of target prescribers, removal of procedural barriers, and development of tools to facilitate and support prescribing. These concrete interventions can help inform other institutions interested in expanding MOUD access., Competing Interests: Author disclosures The authors report no actual or potential conflicts of interest with regard to this article., (Copyright © 2021 Frontline Medical Communications Inc., Parsippany, NJ, USA.)

Prenatal alcohol exposure is the leading preventable cause of cognitive deficit in developed countries and can lead to fetal alcohol spectrum disorder (FASD). This term encompasses a wide range of physical, mental, behavioral, and cognitive effects that result from damage caused by exposure to alcohol during intrauterine life. Alcohol consumption among the general population is common in Eastern European countries and especially among women at risk of social exclusion, who are the ones who lose or give up custody of their children. A high number of these children are adopted in Spain and many of them present neurocognitive and behavioral disorders, causing FASD to be a public health problem in our country. In many occasions this clinical spectrum is delayed or under-diagnosed due to the overlapping of neuropsychological symptoms caused by the abandonment. A neurocognitive and behavioral profile specific for FASD has not been defined and all the symptoms are common to other etiologies. The aim of this work is to review the neuropsychological profile in the diagnosis of FASD., (Copyright © 2021 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.)

Objectives: To determine the prevalence of substance abuse among our pregnant women and the characteristics of their pregnancies, deliveries and new-born infants., Methods: Retrospective observational study of infants born between January 1, 2009 and December 31, 2017 in our centre to substance-abusing mothers and compared with our 2002-2008 study., Results: Heroin use is decreasing, while cannabis and methamphetamine use are increasing. We observed a decrease in withdrawal associated with methadone and benzodiazepine use and an increase in breastfeeding in benzodiazepine and cannabis users. The infants of mothers who use heroin and cocaine are discharged to the mother's home less often. We observed a predominance of substance abuse among Spanish women except for methamphetamines, where the majority of users are Filipino., Conclusions: The increase in cannabis use and the decrease in heroin and cocaine use have improved gestational control. Methamphetamine use is associated with serious social risks., (Copyright © 2020 Elsevier España, S.L.U. All rights reserved.)

What Is Known and Objective: Acyclovir and valacyclovir are commonly used antivirals with good general tolerance. Despite their good safety profile, they can cause systemic adverse effects, such as neurotoxicity, which are less frequent and known. The objective of this review was to collect all the reported cases of neurotoxicity associated with acyclovir and valaciclovir published in the literature and characterize their clinical course and interventions., Methods: A systematic review of cases was carried out following the guidelines established by "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" (PRISMA). The research was carried out using the PubMed-Medline and Embase databases, between July 1984 and March 2021., Results and Discussion: A total of 119 cases with neurotoxicity mainly related to acyclovir (n = 88; 73.9%), followed by valaciclovir (n = 35; 29.4%) were analysed. 49.6% (n = 59) were men with a mean age of 59.5 years ± 21.1 (0.5-88). In 83.3% of the cases, renal impairment was documented and 57.1% (n = 68) with end-stage renal disease. The administered dose was higher than the renal adjustment recommendations in 59.7% of the cases. The global mean of onset of symptoms was 3.1 days ± 4.3 (0.2-28) after the start of antivirals. The mean recovery time was 9.8 days ± 21.7 (0.2-180). 74.4% of the patients had a recovery of ≤7 days, 15.9% between 8 and 15 days and 9.8% > 15 days., What Is New and Conclusion: The neurotoxicity induced by acyclovir and its derivative valacyclovir is a poorly known and rare adverse effect that can occur mainly in patients with advanced age and impaired renal function. The most characteristic symptoms are confusion, altered level of consciousness, hallucinations, agitation and dysarthria. The basis of treatment is the discontinuation of the antiviral, and in some cases, it may require additional clearance by dialysis., (© 2021 John Wiley & Sons Ltd.)

Chronic hepatitis B virus (HBV) infection affects more than 250 million people worldwide, which greatly increases the risk for terminal liver diseases, such as liver cirrhosis and hepatocellular carcinoma (HCC). Even though current approved antiviral therapies, including pegylated type I interferon (IFN) and nucleos(t)ide analogs, can effectively suppress viremia, HBV infection is rarely cured. Since HBV exhibits a narrow species tropism and robustly infects only humans and higher primates, progress in HBV research and preclinical testing of antiviral drugs has been hampered by the scarcity of suitable animal models. Fortunately, a series of surrogate animal models have been developed for the study of HBV. An increased understanding of the barriers towards interspecies transmission has aided in the development of human chimeric mice and has greatly paved the way for HBV research in vivo, and for evaluating potential therapies of chronic hepatitis B. In this review, we summarize the currently available animal models for research of HBV and HBV-related hepadnaviruses, and we discuss challenges and future directions for improvement.

Background: In India, caregivers are an integral part of the illness experience, especially in cancer, to the extent that they can become proxy decision-makers for the patient. Further, owing to acute resource constraints in the Indian healthcare system, it may be difficult for oncologists to assess and elicit questions from each patient/caregiver. Consequently, there is a need to address these unique aspects of oncology care in India to improve patient outcomes and understanding of their illness and treatment. This can be achieved through a Question Prompt List (QPL), a checklist used by care recipients during medical consultations., Recent Findings: This narrative review will first introduce research on the development and effectiveness of the QPL, and then it will highlight current gaps in oncology care in India and explore how the QPL may aid in closing these gaps. A literature search of the empirical research focused on the development, feasibility and acceptability of the QPL in oncology settings was conducted. The final review included 40 articles pertaining to QPL research. Additionally, psycho-oncology research in India centered on information needs and experiences was reviewed. Current Indian psycho-oncology research reports patients' want to be actively involved in their cancer care and a need for more illness information. However, a high demand on physicians' resources and the family caregivers' interference can be barriers to meeting patients' information/communication needs. International research demonstrates that a QPL helps structure and decrease consultation time, improves patient satisfaction with care, and improves the quality of communication during medical encounters., Conclusion: QPLs for Indian patients and caregivers may focus on the scope of medical consultations to address patient needs while influencing the course and content of the patient-caregiver-physician interactions. Further, it can address the resource constraints in Indian oncology care settings, thus reducing the physician's burden., (© 2020 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Nondisclosure of a cancer diagnosis and prognosis is a common practice in many family-centric cultures wherein cancer is viewed negatively, resulting in family carers opposing truthful communication to patients. Oncologists comply with this request for diagnosis and/or prognosis nondisclosure owing to the cultural milieu, often choosing to describe the disease in less threatening terms such as "tumor" or "fever." This review provides a snapshot of existing research exploring diagnosis and prognosis disclosure and nondisclosure from the perspectives of the oncologists, family carers, and the patient with a particular focus on the psychological outcomes for patients who are aware versus not aware of their diagnosis and/or prognosis. Further, this review makes recommendations for future research and practice in cancer diagnosis and prognosis communication in India (e.g., communication skills training for family carers and healthcare providers)., Competing Interests: None

Ankyloglossia, or tongue-tie, is a congenital anomaly in which a short lingual frenulum or a highly attached genioglossus muscle restricts tongue movement. The reported prevalence of neonatal ankyloglossia varies between less than 1 and 12.1% depending upon the study population and criteria used to define and grade ankyloglossia. Our hypothesis was that ankyloglossia had a higher prevalence among our newborn population than previously reported. We conducted an observational, transversal cross-sectional study which included all neonates born in our center between January 1 and December 31, 2018, and actively assessed for tongue-tie. We considered "clinically significant" or "symptomatic" ankyloglossia using the Hazelbaker tool for appearance and function when the mother experienced nipple pain or bruises, or when the neonate had difficulty latching onto the breast. A total of 1392 neonates were born at our center in 2018. Tongue-tie was identified in 645 infants (46.3%), of which 453 were symptomatic (70.2%). Thus, clinically significant ankyloglossia was present in 32.5% of the neonates born in 2018. Their distribution according to Coryllos's types were as follows: 45 type 1 (7.0%), 230 type 2 (35.6%), 321 type 3 (49.8%), and 42 type 4 (6.5%).Conclusion: The prevalence of symptomatic ankyloglossia in our population is higher (32.5%) than studies have reported to date. Actively assessing for tongue-tie increases its diagnosis. What is Known: • There are four types of tongue-tie according to Coryllos (1, 2, 3, and 4), of which the two anterior types (1 and 2) are the most apparent and easy to diagnose. • The reported prevalence of ankyloglossia generally varies from < 1 to 12.1%, although some recent studies report a higher prevalence. What is New: • We found a prevalence of neonatal ankyloglossia of 46.3%, of which 70.2% was symptomatic (clinically significant ankyloglossia was present in 32.5% of the neonates born in 2018 at our hospital). • Actively assessing for ankyloglossia and posterior tongue-ties, which are likely more often undiagnosed, increases its diagnosis.

Measurement of transcutaneous bilirubin (TcB) is widely used to estimate serum bilirubin (SB). However, its reliability depending on skin tone is still controversial. Ethnic classification does not correlate well with skin tone. We aimed to determine the reliability of transcutaneous bilirubin in a multiethnic population based on skin color according to our neonatal skin color scale. We conducted a prospective, observational study comparing SB and TcB among different skin colors. With the blood sample routinely obtained at 48-72 h for the screening of inborn errors of metabolism, we determined SB and TcB with a jaundice meter. We obtained data from 1359 newborns (color 1 337, color 2 750, color 3 249, color 4 23) and analyzed 1549 dyads SB/TcB. Correlation between TcB and serum bilirubin was very good (R 2 = 0.908-0.956), globally and by color group, with slight differences between darker and lighter skin colors. Bland-Altman plots showed different mean bias depending on skin color. Conclusions: Our study not only supports the reliability of TcB to assess SB regardless of skin color, but also supports the fact that TcB tends to overestimate SB in a higher degree in dark-skinned neonates. This may help reduce the number of blood samples for newborns. What is Known: • Jaundice meters are extensively used to diagnose neonatal hyperbilirubinemia, although controversies exist on their reliability depending on skin color. • Only a few studies have analyzed their accuracy in multiethnic populations, but none has used a validated neonatal skin color scale. What is New: • We verified correlation between serum and transcutaneous bilirubin in a multiethnic population depending on skin color after classifying our neonates into color groups with our own validated neonatal skin color scale.

Iron oxide nanoparticles (IONPs) are employed as MRI contrast agents and as effective drug delivery vehicles. However, the limited solubility and biodegradability of these nanoparticles need to be improved for safer biomedical applications. In an attempt to improve the bottlenecks associated with IONPs, the current study focuses on the synthesis of folic acid conjugated, galactoxyloglucan-iron oxide nanoparticles (FAPIONPs), for the loading and controlled release of the encapsulated chemotherapeutic agent doxorubicin (DOX). The as-designed DOX@FAPIONPs induced a dose-dependent increase in cytotoxicity in folate receptor-positive cells through a caspase-mediated programmed cell death pathway while bare DOX demonstrated a non-targeted toxicity profile. Using LC-MS/MS analysis, several major biological processes altered in treated cells, from which, cell cycle, cellular function and maintenance were the most affected. Detailed toxicity studies in healthy mice indicated the absence of any major side effects while bare drugs created substantial organ pathology. Gadolinium-based contrast agents have a risk of adverse effects, including nephrogenic systemic fibrosis overcome by the administration of DOX@FAPIONPs in xenograft mice model. Tumor-targeted biodistribution pattern with a favorable DOX pharmacokinetics will be the driving factor behind the appealing tumor reduction capacity and increased survival benefits demonstrated on solid tumor-bearing mice., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Before choosing psycho-oncology, there was a juncture in my life when I had to select my specialization for further education. It was overwhelming to choose one from all the areas available at that time and be solely responsible for this decision as it had a bearing on not just me, but also on my family. In 2013 (when I decided on my area of specialization), psycho-oncology was a new field. With just a belief to hold onto, that one day psycho-oncology would be widespread and welcomed in Indian cancer care, I pursued this field with dedication and passion. Despite knowing the risk of choosing a career of a barely trodden path, I took the plunge because I believed in its need and that I could contribute to this field meaningfully. Persistent efforts to integrate psycho-oncology into mainstream oncology are being made by psychologists, policymakers, oncologists, social workers and palliative care professionals and I will continuously strive to add my bit to this field. Cancer, as is commonly known, is an illness of the patient, as well as the family. Cancer impacts patients, caretakers, and oncologists. I observed that factors such as culture, age, caretakers beliefs, their perceptions about the illness, society, and the stigma associated with the illness are some of the barriers to truthful disclosure. This is an area within psycho-oncology that interests me and I have dedicated the past few years of my research to knowing it in depth. In this narration, I share with you an encounter with a patient which propelled me certainly and went deeply into psycho-oncology., Competing Interests: None

Shapelets are discriminative segments used to classify time-series instances. Shapelet methods that jointly learn both classifiers and shapelets have been studied in recent years because such methods provide both interpretable results and superior accuracy. The partial area under the receiver operating characteristic curve (pAUC) for a low range of false-positive rates (FPR) is an important performance measure for practical cases in industries such as medicine, manufacturing, and maintenance. In this article, we propose a method that jointly learns both shapelets and a classifier for pAUC optimization in any FPR range, including the full AUC. In addition, we propose the following two extensions for shapelet methods: (1) reducing algorithmic complexity in time-series length to linear time and (2) explicitly determining the classes that shapelets tend to match. Comparing with state-of-the-art learning-based shapelet methods, we demonstrated the superiority of pAUC on UCR time-series data sets and its effectiveness in industrial case studies from medicine, manufacturing, and maintenance.

Nanotechnology-based drug delivery research has largely focused on developing well efficient localized delivery therapeutic agents to overcome the limitations of non-specificity and toxicity of conventional chemotherapy. Herein, we constructed a nanoplatform based on a self-assembled polysaccharide-protein conjugate to deliver anti-tumor drug doxorubicin and gold nanoparticles (DOX@PST-BSA AuNPs) for cancer therapy. The self-assembled DOX@PST-BSA AuNPs exhibited higher stability and thermal properties which enable them for drug delivery via passive targeting. The fluorescent property of the drug contributes to the self-monitoring of NPs Biodistribution in vitro and in vivo. Furthermore, the NPs showed negligible cytotoxicity and tissue accumulation in normal cells in vivo. Importantly, the NPs could load the anti-tumor drug with high encapsulation efficiency and competently delivered into the tumor microenvironment thereby inhibit tumor growth significantly through apoptotic induction. Notably, DOX@PST-BSA AuNPs exhibits low systemic toxicity and very few side effects in vivo. Based on the explored features, these NPs could serve as a promising multifunctional drug delivery nanoplatform for cancer therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ethnic classification does not correlate well with skin tone. As there are no neonatal skin color scales, we aimed to create and validate one of our own. After creating the scale and briefly training our staff, we conducted a prospective, observational study to assess reproducibility and correlation of each scale color with the melanin and erythema indexes and transcutaneous bilirubin. The reliability of our color scale was measured using Kappa agreement (and its 95% confidence interval) and the concordance index by comparing inter-observer classification of neonatal skin color. We also calculated inter-rater agreement with the intraclass correlation coefficient (ICC). The Kendall tau-b correlation coefficient was used to test the correlation between our color scale and the Mexameter® MX 18. We obtained data from 258 newborns. Inter-observer agreement on color assignment was 83.2%. Median melanin index was significantly different among the 4 color groups, whereas erythema index and transcutaneous bilirubin were not.Conclusions: Our proposed neonatal skin color scale correlates well with the melanin index at 24 h of life, increasing from colors 1 to 4, and the only chromophore different among our four color groups is melanin. Scale color assignment is reproducible. Therefore, it can be used to classify neonatal skin color. Further research is warranted to assess the clinical relevance of these findings. What is known: • Classifying neonates by skin color is difficult because to date there are no skin color scales available based on real skin tone regardless of ethnicity or country of origin. • Skin color differs among individuals from a given ethnic group and depends, among others, on melanin and hemoglobin. What is new: • We created a neonatal skin color scale based on real skin color. • We conducted a study to validate it, and confirmed a good inter-observer agreement in color assignment as well as a good correlation between each color in the scale and the median melanin level.

In many legumes, the colonization of roots by rhizobia is via "root hair entry" and its molecular mechanisms have been extensively studied. However, the nodulation of peanuts ( Arachis hypogaea L.) by Bradyrhizobium strains requires an intercellular colonization process called "crack entry," which is understudied. To understand the intercellular crack entry process, it is critical to develop the tools and resources related to the rhizobium in addition to focus on investigating the mechanisms of the plant host. In this study, we isolated a Bradyrhizobium sp. strain, Lb8 from peanut root nodules and sequenced it using PacBio long reads. The complete genome sequence was a circular chromosome of 8,718,147 base-pair (bp) with an average GC content of 63.14%. No plasmid sequence was detected in the sequenced DNA sample. A total of 8,433 potential protein-encoding genes, one rRNA cluster, and 51 tRNA genes were annotated. Fifty-eight percent of the predicted genes showed similarity to genes of known functions and were classified into 27 subsystems representing various biological processes. The genome shared 92% of the gene families with B. diazoefficens USDA 110 T . A presumptive symbiosis island of 778 Kb was detected, which included two clusters of nif and nod genes. A total of 711 putative protein-encoding genes were in this region, among which 455 genes have potential functions related to symbiotic nitrogen fixation and DNA transmission. Of 21 genes annotated as transposase, 16 were located in the symbiosis island. Lb8 possessed both Type III and Type IV protein secretion systems, and our work elucidated the association of flagellar Type III secretion systems in bradyrhizobia. These observations suggested that complex rearrangement, such as horizontal transfer and insertion of different DNA elements, might be responsible for the plasticity of the Bradyrhizobium genome., (Copyright © 2020 Paudel, Liu, Wang, Crook, Maya, Peng, Kelley, Ané and Wang.)

Glutamate excitotoxicity plays a crucial role in the pathogenesis behind the development and progression of several neurodegenerative diseases. The study aimed to investigate the neuroprotective activity of Gallic acid (GA) against glutamate-induced neurotoxicity in primary rat cortex neurons (RCN). Treated the RCNs with GA 25 & 50 μg/ml for 2 h and later treated the cells with 100 μM glutamate (GLU) and incubated for 24 h at 37 °C. The results demonstrated that, the GA improved the antioxidant profile in the cortex neurons and inhibited the production of the proinflammatory cytokine. GA also maintained the Ca 2+ homeostasis, IGF-1 expression, and protected the neurons from glutamate-induced neuronal toxicity. The neuroprotective activity of GA has further confirmed from the results of N-acetylaspartate and expression of microtubule-associated protein-2 expression. The reports suggest that, GA is significantly attenuated the glutamate-induced neurotoxicity and protected neurons from various chemical events that are involved in the pathogenesis of neurotoxicity., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Galactomannan isolated from the fruit rind of Punica granatum was previously reported to have excellent antioxidant, immunomodulatory and anticancer properties against both human and murine cancer cells. This polysaccharide was proved to be an anticancer agent either alone or as an adjuvant to chemotherapy. An exploration leads to the fabrication of silver nanoparticles with an average size around 30 nm and a negative surface charge of 35.2 mV using this biopolymer which acted both as reducing and capping agent and displayed good stability and biocompatibility. UV-vis spectrum of the aqueous medium containing silver nanoparticles showed an absorption peak at around 440 nm. The nanoparticles displayed an upgraded and selective cytotoxicity towards human adenocarcinoma, colorectal carcinoma and hepatocellular carcinoma cells. The induction of cancer cell toxicity was proved to be through the induction of programmed cell death pathway mediated with the active involvement of caspases. The significant anti-metastatic properties will further favour the safer in vivo application of these silver nanoparticles against neoplasia. The nontoxic nature of polysaccharide endowed the resultant silver nanoparticles with excellent biocompatibility towards red blood cells and extended the biomedical potential of this candidate. Hence, the surfactant-free green method mediated orchestration of biogenic silver nanoparticles resembled a potential theransonstic nano-construct with synergistic anticancer and immunomodulatory potential in a single platform., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: There is evidence that delivery room resuscitation of very preterm infants often deviates from internationally recommended guidelines. There were no published data in Spain regarding the quality of neonatal resuscitation. Therefore, we decided to evaluate resuscitation team adherence to neonatal resuscitation guidelines after birth in very preterm infants., Methods: We conducted an observational study. We video recorded resuscitations of preterm infants < 32 weeks' gestational age and evaluated every step during resuscitation according to a score-sheet specifically designed for this purpose, following Carbine's method, where higher scores indicated that more intense resuscitation maneuvers were required. We divided the score achieved by the total possible points per patient to obtain the percentage of adherence to the algorithm. We also compared resuscitations performed by staff neonatologists to those performed by pediatricians on-call. We compared percentages of adherence to the algorithm with the Chi-square test for large groups and Fisher's exact test for smaller groups. We compared assigned Apgar scores with those given after analyzing the recordings and described them by their median and interquartile range. We measured the interrater agreement between Apgar scores with Cohen's kappa coefficient. Linear and logarithmic regressions were drawn to characterize the pattern of algorithm adherence. Statistical analysis was performed using SPSS V.20. A p-value < 0.05 was considered significant. Our Hospital Ethics Committee approved this project, and we obtained parental written consent beforehand., Results: Sixteen percent of our resuscitations followed the algorithm. The number of mistakes per resuscitation was low. Global adherence to the algorithm was 80.9%. Ventilation and surfactant administration were performed best, whereas preparation and initial steps were done with worse adherence to the algorithm. Intubation required, on average, 2.2 attempts; success on the first attempt happened in 33.3% of cases. Only 12.5% of intubations were achieved within the allotted 30 s. Many errors were attributable to timing. Resuscitations led by pediatricians on-call were performed as correctly as those by staff neonatologists., Conclusions: Resuscitation often deviates from the internationally recognized algorithm. Perfectly performed resuscitations are infrequent, although global adherence to the algorithm is high. Neonatologists and pediatricians need intubation training.

Al exposure causes an alteration in the several ions in the body and causes toxicity. Such as apoptosis, oxidative stress, disruption in neuronal transport, mitochondrial damage, excitotoxicity, generation of inflammatory mediators, and microglial activation. These multiple mechanisms lead to the several neurodegenerative diseases, including sporadic amyotrophic lateral sclerosis (sALS). The study aims to unravel the mechanisms behind the neuroprotective effects of wedelolactone (WL) and gallic acid (GA) against aluminium-induced neurodegeneration and thereby to unlock a platform to find a cure for sALS. We studied the neuroprotective effects of WL (100 & 200 mg/kg) and GA (100 & 200 mg/kg) using aluminium chloride (AlCl 3 )-induced neurodegeneration model. The study was conducted using male Wistar rats. We assessed the effects of WL and GA on motor learning ability, motor coordination, locomotor activity, cytokine production, BDNF, glutathione peroxidase (GPx), m-calpain, caspase-3 inhibition and L-glutamate level. The study suggests that the treatment with WL and GA could protect the motor neurons from the toxicity that caused by Al via improving the antioxidant status, BDNF, and by preventing glutamate excitotoxicity. Also, WL and GA are found to be effective in inhibiting caspase-3 activation and downregulating inflammatory cytokines. WL and GA also found effective in improving the motor learning abilities and motor coordination in rats. The protective effects of the WL and GA were further confirmed from histopathological results. WL and GA prevent the neurofibrillary tangle formation and neuronal damage. The study concluded that the WL and GA were dose-dependently effective in managing the AlCl 3 -induced neurodegeneration., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: Prenatal methamphetamine exposure is related to prematurity, fetal growth restriction, neurobehavioral effects and long-term motor and cognitive sequelae., Patient Presentation: We report the case of a newborn from a Filipina with no prenatal care with a complex brain malformation. Methamphetamine was identified in maternal and neonatal urine and in maternal hair, raising our suspicion of methamphetamine as a cause of this malformation., Discussion: Methamphetamine abuse is a growing problem worldwide. There are little data on its effect on the fetus. To our knowledge, no fetal brain abnormalities have been associated with its use. In our case, the lack of antenatal control does not allow us to date when this malformation appeared., Conclusion: The aim of our report is to generate awareness of the possible association between methamphetamine abuse during pregnancy and central nervous system malformations.

Sugarcane ( Saccharum spp.) is an important economic crop, contributing up to 80% of table sugar used in the world and has become a promising feedstock for biofuel production. Sugarcane production has been threatened by many diseases, and fungicide applications for disease control have been opted out for sustainable agriculture. Orange rust is one of the major diseases impacting sugarcane production worldwide. Identifying quantitative trait loci (QTLs) and developing diagnostic markers are valuable for breeding programs to expedite release of superior sugarcane cultivars for disease control. In this study, an F 1 segregating population derived from a cross between two hybrid sugarcane clones, CP95-1039 and CP88-1762, was evaluated for orange rust resistance in replicated trails. Three QTLs controlling orange rust resistance in sugarcane (qORR109, qORR4 and qORR102) were identified for the first time ever, which can explain 58, 12 and 8% of the phenotypic variation, separately. We also characterized 1,574 sugarcane putative resistance ( R ) genes. These sugarcane putative R genes and simple sequence repeats in the QTL intervals were further used to develop diagnostic markers for marker-assisted selection of orange rust resistance. A PCR-based Resistance gene-derived maker, G1 was developed, which showed significant association with orange rust resistance. The putative QTLs and marker developed in this study can be effectively utilized in sugarcane breeding programs to facilitate the selection process, thus contributing to the sustainable agriculture for orange rust disease control.

We present a computational investigation of binding affinity of different types of drugs with chitin nanocarriers. Understanding the chitn polymer-drug interaction is important to design and optimize the chitin based drug delivery systems. The binding affinity of three different types of anti-bacterial drugs Ethionamide (ETA) Methacycline (MET) and Rifampicin (RIF) with amorphous chitin nanoparticles (AC-NPs) were studied by integrating computational and experimental techniques. The binding energies (BE) of hydrophobic ETA, hydrophilic MET and hydrophobic RIF were -7.3kcal/mol, -5.1kcal/mol and -8.1kcal/mol respectively, with respect to AC-NPs, using molecular docking studies. This theoretical result was in good correlation with the experimental studies of AC-drug loading and drug entrapment efficiencies of MET (3.5±0.1 and 25± 2%), ETA (5.6±0.02 and 45±4%) and RIF (8.9±0.20 and 53±5%) drugs respectively. Stability studies of the drug encapsulated nanoparticles showed stable values of size, zeta and polydispersity index at 6°C temperature. The correlation between computational BE and experimental drug entrapment efficiencies of RIF, ETA and MET drugs with four AC-NPs strands were 0.999 respectively, while that of the drug loading efficiencies were 0.854 respectively. Further, the molecular docking results predict the atomic level details derived from the electrostatic, hydrogen bonding and hydrophobic interactions of the drug and nanoparticle for its encapsulation and loading in the chitin-based host-guest nanosystems. The present results thus revealed the drug loading and drug delivery insights and has the potential of reducing the time and cost of processing new antibiotic drug delivery nanosystem optimization, development and discovery., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Tunable pH and redox responsive polymer was prepared using γ-polyglutamic acid (γ-PGA) with linker 3-mercaptopropionic acid (3-MPA) (γ-PGA&#95;SH) via oxidation to obtain redox responsive disulfide (γ-PGA&#95;SS) backbone and adipic acid dihydrazide (ADH) (γ-PGA&#95;SS&#95;ADH) with hydrazide functional group for pH responsiveness. Further curcumin (Cur) was conjugated through hydrazone bond of the γ-PGA&#95;SS&#95;ADH via Schiff base reaction to obtain (γ-PGA&#95;SS&#95;ADH&#95;Cur). The prepared systems were characterized by Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, Electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-Qq-TOF-MS/MS) and Solid state nuclear magnetic resonance (SS NMR) techniques. γ-PGA&#95;SS&#95;ADH&#95;Cur formed self-assembled core shell nanoparticles (NPs) in existence of stabilized aqueous medium. γ-PGA&#95;SS&#95;ADH&#95;Cur NPs maintained its stability in physiological condition. NPs tunable Cur release and cytotoxicity were observed for γ-PGA&#95;SS&#95;ADH&#95;Cur NPs in both acidic and redox conditions mimicking the cancer microenvironment. γ-PGA&#95;SS&#95;ADH&#95;Cur NPs uptake study showed via endocytosis mechanism resulted in the lysosomal entrapment of these NPs within the cell. γ-PGA&#95;SS&#95;ADH&#95;Cur NPs exhibited a dual stimuli responsive drug delivery and can be used as a smart and potential drug delivery system in cancer microenvironment., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: The protocol for the management of mild cranioencephalic trauma in the emergency department was changed in July 2013. The principal innovation was the replacement of systematic X-ray in infants with clinical observation. The aims of this study were to determine whether there was, 1) a reduction in the ability to detect traumatic brain injury (TBI) in the initial visit to Emergency, and 2) a change in the number of requests for imaging tests and hospital admissions., Methodology: This was a retrospective, descriptive, observational study. Two periods were established for the study: Period 1 (1/11/2011-30/10/2012), prior to the implementing of the new protocol, and Period 2 (1/11/2013-30/10/2014), following its implementation. The study included visits to the emergency department by children≤2 years old for mild cranioencephalic trauma (Glasgow Scale modified for infants≥14) of ≤24hours onset., Results: A total of 1,543 cases were included, of which 807 were from Period 1 and 736 from Period 2. No significant differences were observed as regards sex, age, mechanism, or risk of TBI. More cranial fractures were detected in Period 1 than in Period 2 (4.3% vs 0.5%; P<.001), without significant changes in the detection of TBI (0.4% vs 0.3%; P=1). However, there were more cranial X-rays (49.7% vs 2.7%; P<.001) and more ultrasounds (2.1% vs 0.4%; P<.001) carried out, and also fewer hospital admissions (8.3% vs 3.1%; P<.001). There were no significant differences in the number of computerised tomography scans carried out (2% vs 3%; P=.203)., Conclusions: The use of clinical observation as an alternative to cranial radiography leads to a reduction in the number of imaging tests and hospital admissions of infants with mild cranioencephalic trauma, without any reduction in the reliability of detecting TBI. This option helps to lower the exposure radiation by the patient, and is also a more rational use of hospital resources., (Copyright © 2016 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.)

Aluminium (Al) is the most common metal and widely distributed in our environment. Al was first isolated as an element in 1827, and its use began only after 1886. Al is widely used for industrial applications and consumer products. Apart from these it is also used in cooking utensils and in pharmacological agents, including antacids and antiperspirants from which the element usually enters into the human body. Evidence for the neurotoxicity of Al is described in various studies, but still the exact mechanism of Al toxicity is not known. However, the evidence suggests that the Al can potentiate oxidative stress and inflammatory events and finally leads to cell death. Al is considered as a well-established neurotoxin and have a link between the exposure and development of neurodegenerative diseases, including Amyotrophic Lateral Sclerosis (ALS), Alzheimer's disease (AD), dementia, Gulf war syndrome and Parkinsonism. Here, we review the detailed possible pathogenesis of Al neurotoxicity. This review summarizes Al induced events likewise oxidative stress, cell mediated toxicity, apoptosis, inflammatory events in the brain, glutamate toxicity, effects on calcium homeostasis, gene expression and Al induced Neurofibrillary tangle (NFT) formation. Apart from these we also discussed animal models that are commonly used for Al induced neurotoxicity and neurodegeneration studies. These models help to find out a better way to treat and prevent the progression in Al induced neurodegenerative diseases., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Colon cancer is one of the major causes of cancer deaths worldwide. Even after surgical resection and aggressive chemotherapy, 50% of colorectal carcinoma patients develop recurrent disease. Thus, the rationale of developing new therapeutic approaches to improve the current chemotherapeutic regimen would be highly recommended. There are reports on the effectiveness of combination chemotherapy in colon cancer and it has been practiced in clinics for long time. These approaches are associated with toxic side effects. Later, the drug delivery research had shown the potential of nanoencapsulation techniques and active targeting as an effective method to improve the effectiveness of chemotherapy with less toxicity. This current focus article provides a brief analysis of the ongoing research in the colon cancer area using the combinatorial nanomedicines and its outcome., (© 2015 Wiley Periodicals, Inc.)

The processes of ossification sequences are poorly investigated for birds in general, even for domestic and experimental species and when it comes to the waterfowl it is almost negligible. Such sequences constitute a rich source of data on character evolution, and may even provide phylogenetic information. A pre-hatch developmental study on ossification sequences of axial and appendicular skeletal system in Kuttanad duck embryos was undertaken using 78 viable embryos. From day 3 to day 7 of incubation no ossification densities were seen both by alizarin red staining and computerized radiography. The first indication of ossification as small ossification centers in skull bones, clavicle, scapula, humerus, radius and ulna in forelimb and ilium, pubis femur and fibula in hind limb were observed on the 9(th) day of incubation. The ossification of the body of the ribs started at the 11(th) day of incubation towards the proximal extremity. On day 13(th) the ossification process of vertebrae was started from cervical end. The variation in appearance of the ossification centers in different bones at different stages of incubation period suggests relative importance of phylogeny to the sequences.

Aim: To observe the light and scanning electron microscopy (SEM) of the caprine tubal tonsil., Materials and Methods: The study was conducted on six crossbred male goats of 6 months of age. From the median sections of the head, tissue pieces from the nasopharynx around the auditory tube were collected and fixed for histology and SEM., Results: Tonsillar lymphoid tissue was located in the nasopharynx ventral to the auditory tube opening in the lateral wall of the pharynx. The height of the surface epithelium of the tubal tonsil measured 80.17±1.08 µm and was a pseudostratified ciliated columnar type with basal, supporting, and goblet cells. Above the dome of lymphoid nodules, the epithelium was modified into a follicle associated epithelium (FAE), also called lympho-epithelium or reticular epithelium and was characterized by the absence of goblet cells and cilia, reduced number of cell layers, and a large number of lymphoid cells due to interrupted basement membrane. The height of FAE was smaller than that of the surface epithelium and measured 34.33±0.92 µm. The surface of tubal tonsil showed folds and invaginations, which formed crypts. The lamina propria-submucosa underneath the epithelium was formed by the meshwork of reticular and, thin and loose collagen fibers with dome-like accumulation of lymphoid nodules. In the secondary lymphoid nodules, a corona, parafollicular area, and interfnodular area were observed. The average number of lymphoid nodules counted per field under low power magnification of microscope was 1.17±0.17, and the internodular distance was 34.00±4.37 µm. The mean diameter of lymphoid nodules was 566.67±11.45 µm and the lymphocyte count per nodule was 14741.67±174.36. The number of plasma cells counted per field under low power was 44.38±2.90 below the surface epithelium. The tubal tonsil was not encapsulated. In SEM, the surface epithelium of the tubal tonsils presented ciliated cells, microvillus (MV) cells, and goblet cells. The region of FAE possessed Type-I and Type-II MV cells and microfold (M) cells in between., Conclusion: It was concluded that the tubal tonsils were well developed in goats, which might serve as a means of protection against the spread of infection to the middle ear cavity.

Nanogels are hydrogels having size in nanoregime, which is composed of cross-linked polymer networks. The advantages of nanogels include stimuli-responsive nature, easy drug loading, and higher drug-loading capacity, physical stability, versatility in design, stability of entrapped drug, and controlled release of the anti-inflammatory, antimicrobial, protein, peptide and anticancer drugs. Stimuli-responsive nature of nanogel is of particular importance in anticancer and anti-inflammatory drug delivery, as cancer and inflammation are associated with acidic pH, heat generation, and change in ionic content. Nanogels composed of muco-adhesive polymers provide prolonged residence time and increase the ocular availability of loaded drugs. By forming suitably sized complex with proteins or by acting as artificial chaperones, they thus help to keep the proteins and enzymes in proper confirmation necessary for exerting biological activity; nanogels can increase the stability and activity of protein/peptide drugs. Better drug penetrations achieved by prolonged contact with skin contribute much in transdermal drug delivery. When it comes to cancer drug delivery, the presence of multiple interactive functional groups in nanogels different targeting agents can be conjugated for delivery of the selective drugs. This review focuses on applications of nanogels in cancer drug delivery and imaging, anti-inflammatory, anti-psoriatic, transdermal, ocular and protein/peptide drug delivery and therapy., (© 2015 Wiley Periodicals, Inc.)

Polymorphonuclear leukocytes (PMNs) provide the primary host defence against invading pathogens by producing reactive oxygen species (ROS) and microbicidal products. However, few pathogens can survive for a prolonged period of time within the PMNs. Additionally their intracellular lifestyle within the PMNs protect themselves from the additional lethal action of host immune systems such as antibodies and complements. Antibiotic delivery into the intracellular compartments of PMNs is a major challenge in the field of infectious diseases. In order to deliver antibiotics within the PMNs and for the better treatment of intracellular bacterial infections we synthesized rifampicin (RIF) loaded amorphous chitin nanoparticles (RIF-ACNPs) of 350±50 nm in diameter. RIF-ACNPs nanoparticles are found to be non-hemolytic and non-toxic against a variety of host cells. The release of rifampicin from the prepared nanoparticles was ∼60% in 24 h, followed by a sustained pattern till 72 h. The RIF-ACNPs nanoparticles showed 5-6 fold enhanced delivery of RIF into the intracellular compartments of PMNs. The RIF-ACNPs showed anti-microbial activity against Escherichia coli, Staphylococcus aureus and a variety of other bacteria. In summary, our results suggest that RIF-ACNPs could be used to treat a variety of intracellular bacterial infections., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Salmonella Paratyphi A is a food-borne Gram-negative pathogen and a major public health challenge in the developing world. Upon reaching the intestine, S. Paratyphi A penetrates the intestinal epithelial barrier; and infects phagocytes such as macrophages and dendritic cells. S. Paratyphi A surviving within macrophages is protected from the lethal action of antibiotics due to their poor penetration into the intracellular compartments. Hence we have developed chloramphenicol loaded chondroitin sulfate (CS-Cm Nps) and dextran sulfate (DS-Cm Nps) nanoparticles through ionotropic-gelation method for the intracellular delivery of chloramphenicol. The size of these nanoparticles ranged between 100 and 200 nm in diameter. The encapsulation efficiency of both the nanoparticles was found to be around 65%. Both the nanoparticles are found to be non-hemolytic and non-toxic to fibroblast and epithelial cells. The prepared nanoparticles exhibited sustained release of the drug of up to 40% at pH 5 and 20-25% at pH 7.0 after 168 h. The anti-microbial activities of both nanoparticles were tested under in vitro and ex vivo conditions. The delivery of DS-Cm Nps into the intracellular compartments of the macrophages was 4 fold more compared to the CS-Cm Nps which lead to the enhanced intracellular antimicrobial activity of Ds-Cm Nps. Enhanced anti-microbial activity of Ds-Cm Nps was further confirmed in an ex vivo chicken intestine infection model. Our results showed that Cm loaded DS Nps can be used to treat intracellular Salmonella infections., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Lung cancer, associated with the up-regulated epidermal growth factor receptor (EGFR) led to the development of EGFR targeted anticancer therapeutics. The biopolymeric nanoparticles form an outstanding system for the targeted delivery of therapeutic agents. The present work evaluated the in vitro effects of chitosan cross-linked γ-poly(glutamic acid) (γ-PGA) nanoparticles (Nps) loaded with docetaxel (DTXL) and decorated with Cetuximab (CET), targeted to EGFR over-expressing non-small-cell-lung-cancer (NSCLC) cells (A549). CET-DTXL-γ-PGA Nps was prepared by ionic gelation and CET conjugation via EDC/NHS chemistry. EGFR specificity of targeted Nps was confirmed by the higher uptake rates of EGFR +ve A549 cells compared to that of EGFR -ve cells (NIH3T3). The cytotoxicity of Nps quantified using cell based (MTT/LDH) and flowcytometry (Cell-cycle analysis, Annexin V/PI and JC-1) assays showed superior antiproliferative activity of CET-DTXL-γ-PGA Nps over DTXL-γ-PGA Nps. The A549 cells treated with CET-DTXL-γ-PGA NPs underwent a G2/M phase cell cycle arrest followed by reduction in mitochondrial membrane potential of A549 cells, inducing apoptosis and necrosis resulting in enhanced cancer cell death. CET-DTXL-γ-PGA Nps exhibited enhanced cellular internalization and therapeutic activity, by actively targeting EGFR on NSCLC cells and hence could be an effective alternative to non-specific, conventional chemotherapy by increasing its efficiency by many folds., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Receptor targeted therapy is advantageous in overcoming the toxicity burden of conventional cancer chemotherapeutics. Over expression of epidermal growth factor receptor (EGFR) on cancer cells and its role in metastasis, malignancy and drug resistance in many human cancers lead to its selection as a promising target for cancer treatment. The present work investigated the preparation and characterization of docetaxel (DTXL) loaded gamma-poly (glutamic acid) (gamma-PGA) nanoparticles (Nps) conjugated with EGFR antibody (Cetuximab, CET) targeted to colon cancer cells (HT-29), highly over expressing EGFR. The flow cytometric analysis revealed two fold increased cellular uptake of CET-DTXL-gamma-PGA Nps by HT-29 (EGFR +ve) cells compared to that of IEC-6 (EGFR-ve) cells confirming the active targeting. Cytotoxicity assays (MTT and LDH) showed superior anti-proliferative activity of CET-DTXL-gamma-PGA NPs over DTXL-gamma-PGA Nps against HT-29 cells. The cell cycle analysis indicated that CET-DTXL-gamma-PGA NPs induced cell death in enhanced percentage of HT-29 cells by undergoing cell cycle arrest in G2/M phase compared to that of DTXL-gamma-PGA Nps. The mechanism of cancer cell death was analyzed via apoptotic and mitochondrial membrane potential assays and showed that targeted Nps treatment reduced the mitochondrial membrane potential thereby inducing enhanced HT-29 cell death (apoptosis and necrosis). The biodistribution of targeted and non-targeted Nps were analyzed in vivo in Swiss albino mice using NIR imaging. ICG-CET-DTXL-gamma-PGA Nps (targeted) and ICG-DTXL-gamma-PGA Nps (non-targeted) followed the similar biodistribution pattern in vivo, but with different elimination time. In short, CET-DTXL-gamma-PGA nanoparticles enhance the tumor selective therapeutic efficacy for colon cancer.

Tenosynovial giant cell tumor (TGCT) is a benign proliferative lesion of unclear etiology. It is predominantly monoarticular and involves the synovium of the joint, tendon sheath, and bursa. TGCT of the temporomandibular joint (TMJ) is rare and aggressive resulting in destruction of surrounding structures. The diagnosis may be suggested by imaging, mainly by the MR features and PET/CT, and confirmed by histopathology. We describe the case of a 50-year-old man who presented with right-sided hearing loss, tinnitus and TMJ pain. Pathology revealed tenosynovial giant cell tumor with chondroid metaplasia. Six years later he developed a recurrence, which was documented to our knowledge for the first time with CT, MR and FDG PET/CT imaging.

Nanogels are hydrogels with nanometer-scale three-dimensional networks of physically or chemically cross-linked chains. Nanogels have attracted much interest in recent years for various biomedical applications such as drug delivery systems and bioimaging owing to their specific properties of size tunability and intrinsic hydrophilic surfaces. Nanogels are generally classified either as natural polymer-based or synthetic polymer-based nanogels. Natural polymer-based nanogels are considered better candidates for drug delivery than synthetic polymer-based nanogels. This review summarizes the role of natural polymer-based nanogels, especially carbohydrate-based nanogels as drug and gene delivery systems.

Nanoparticle mediated delivery of antineoplastic agents, functionalized with monoclonal antibodies has achieved extraordinary potential in cancer therapy. The objective of this study was to develop a drug delivery system comprising O-carboxymethyl chitosan (O-CMC) nanoparticles, surface-conjugated with Cetuximab (Cet) for targeted delivery of paclitaxel (PTXL) to Epidermal Growth Factor Receptor (EGFR) over-expressing cancer cells. Nanoparticles around 180±35nm and negatively charged were prepared through simple ionic gelation technique. The alamar blue assay indicated that these targeted nanoparticles displayed a superior anticancer activity compared to non-targeted nanoparticles. The nanoformulation triggered enhanced cell death (confirmed by flow cytometry) due to its higher cellular uptake. The selective uptake of Cet-PTXL-O-CMC nanoparticles by EGFR +VE cancer cells (A549, A431 and SKBR3) compared to EGFR -VE MIAPaCa-2 cells confirms the active targeting and delivery of PTXL via the targeted nanomedicine. Cet-PTXL-O-CMC nanoparticles can be used a promising candidate for the targeted therapy of EGFR over expressing cancers., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Nanogels are nanosized hydrogel particles formed by physical or chemical cross-linked polymer networks. The advantageous properties of nanogels related to the ability of retaining considerable amount of water, the biocompatibility of the polymers used, the ability to encapsulate and protect a large quantity of payload drugs within the nanogel matrix, the high stability in aqueous media, their stimuli responsively behavior potential, and the versatility in release drugs in a controlled manner make them very attractive for use in the area of drug delivery. The materials used for the preparation of nanogels ranged from natural polymers like ovalbumin, pullulan, hyaluronic acid, methacrylated chondroitin sulfate and chitosan, to synthetic polymers like poly (N-isopropylacrylamide), poly (Nisopropylacrylamide- co-acrylic acid) and poly (ethylene glycol)-b-poly (methacrylic acid). The porous nanogels have been finding application as anti-cancer drug and imaging agent reservoirs. Smart nanogels responding to external stimuli such as temperature, pH etc can be designed for diverse therapeutic and diagnostic applications. The nanogels have also been surface functionalized with specific ligands aiding in targeted drug delivery. This review focus on stimuli-sensitive, multi-responsive, magnetic and targeted nanogels providing a brief insight on the application of nanogels in cancer drug delivery and imaging in detail.

Intracellular bacterial infections are recurrent, persistent and are difficult to treat because of poor penetration and limited availability of antibiotics within macrophages and epithelial cells. We developed biocompatible, 200 nm sized tetracycline encapsulated O-carboxymethyl chitosan nanoparticles (Tet-O-CMC Nps) via ionic gelation for its sustained delivery of Tet into cells. S. aureus binds and aggregates with Tet-O-CMC Nps increasing drug concentrations at the infection site. Tet-O-CMC Nps were sixfold more effective in killing intracellular S. aureus compared to Tet alone in HEK-293 and differentiated THP1 macrophage cells proving it to be an efficient nanomedicine to treat intracellular S. aureus infections., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Chitosan (CS) and its carboxymethyl derivatives are smart biopolymers that are non-toxic, biocompatible and biodegradable, and, hence, suitable for various biomedical applications, such as drug delivery, gene therapy and tissue engineering. Curcumin is a major chemotherapeutic agent with antioxidant, anti-inflammatory, anti-proliferative, anticancer and antimicrobial effects. However, the potential of curcumin as a chemotherapeutic agent is limited by its hydrophobicity and poor bioavailability. In this work, we developed a nanoformulation of curcumin in a carboxymethyl chitosan (CMC) derivative, N,O-carboxymethyl chitosan (N,O-CMC). The curcumin-loaded N,O-CMC (curcumin-N,O-CMC) nanoparticles were characterized using DLS, AFM, SEM, FT-IR and XRD. DLS studies revealed nanoparticles with a mean diameter of 150 ± 30 nm. AFM and SEM confirmed that the particles have a spherical morphology within the size range of 150 ± 30 nm. Curcumin was entrapped with in N,O-CMC nanopartcles with an efficiency of 80%. The in vitro drug-release profile was studied at different pH (7.4 and 4.5) at 37°C for different incubation periods with and without lysozyme. Cytotoxicity studies using MTT assay indicated that curcumin-N,O-CMC nanoparticles showed specific toxicity towards cancer cells and non-toxicity to normal cells. Cellular uptake of curcumin-N,O-CMC nanoparticles was analyzed by fluorescence microscopy and was reconfirmed by flow cytometry. Overall, these results indicate that like previously reported curcumin loaded O-CMC nanoparticles, N,O-CMC will also be an efficient nanocarrier for delivering curcumin to cancer cells.

Six thermophilic enzymes from Thermus thermophilus were used to construct an 'artificial bio-synthetic pathway' for the production of 2-deoxyribose 5-phosphate from fructose. By a simple operation using six recombinant Escherichia coli strains producing the thermophilic enzymes, respectively, fructose was converted to 2-deoxyribose 5-phosphate with a molar yield of 55%., (Copyright 2010 Elsevier B.V. All rights reserved.)

We have assessed the accuracy of a representative set of currently available approximate kinetic-energy functionals used within the frozen-density embedding scheme for the NgAuF (Ng=Ar, Kr, Xe) molecules, which we partitioned into a Ng and a AuF subsystem. Although it is weak, there is a covalent interaction between these subsystems which represents a challenge for this subsystem density functional theory approach. We analyzed the effective-embedding potentials and resulting electron density distributions and provide a quantitative analysis of the latter from dipole moment differences and root-mean-square errors in the density with respect to the supermolecular Kohn-Sham density functional theory reference calculation. Our results lead to the conclusion that none of the tested approximate kinetic-energy functionals performs well enough to describe the bond between the noble gas and gold adequately. This observation contributes to the growing evidence that the current procedure to obtain approximate kinetic-energy functionals by reparametrizing functionals obtained via the "conjointness" hypothesis of Lee, Lee, and Parr [Phys. Rev. A 44, 768 (1991)] is insufficient to treat metal-ligand interactions with covalent character.