An 85-Year-Old Man with Fever, Dyspnea, and Dry Cough Diagnosed with Idiopathic Hypereosinophilic Syndrome, Successfully Treated with High-Dose Corticosteroids.

BACKGROUND Idiopathic hypereosinophilic syndrome (I-HES) is a rare disease diagnosed as absolute eosinophil count >1500 cells/µl and end-organ involvement attributable to tissue eosinophilia with no secondary cause of underlying eosinophilia. The mean age of presentation for I-HES is 44 years. The skin, lungs, and gastrointestinal (GI) system are most common sites of presenting manifestations, including fatigue, cough, dyspnea, myalgias, angioedema, rash, fever, nausea, and diarrhea. Although cardiac and neurologic symptoms are less common at presentation, they can be life-threatening. CASE REPORT We report the case of an 85-year-old man who presented with fever, malaise, and loss of appetite for 3 weeks, followed by dyspnea and dry cough for 2 weeks. His absolute eosinophil count was 9000 cells/µl, which was not responding to empirical antibiotic therapy, with worsening of symptoms, suggesting a non-infective origin. He was then extensively evaluated to establish underlying an etiology for specific treatment, which was negative for common causes like atypical infections, malignancy, and autoimmune disorders. He was then started on corticosteroid therapy to overcome an exaggerated immune response and reduce inflammation-related injury, to which he responded well. On follow-up, hypereosinophilia was fully cured, with reversal of end-organ involvement including myocarditis and pneumonitis. CONCLUSIONS This report shows that idiopathic HES can present with various clinical features and that accurate diagnosis, excluding known causes of eosinophilia, and early management are essential to prevent long-term organ damage. Our patient responded to prompt treatment with high-dose corticosteroids.

Unraveling the intricate relationship: Influence of microbiome on the host immune system in carcinogenesis.

BACKGROUND: Cancer is an outcome of various disrupted or dysregulated metabolic processes like apoptosis, growth, and self-cell transformation. Human anatomy harbors trillions of microbes, and these microbes actively influence all kinds of human metabolic activities, including the human immune response. The immune system which inherently acts as a sentinel against microbes, curiously tolerates and even maintains a distinct normal microflora in our body. This emphasizes the evolutionarily significant role of microbiota in shaping our adaptive immune system and even potentiating its function in chronic ailments like cancers. Microbes interact with the host immune cells and play a part in cancer progression or regression by modulating immune cells, producing immunosuppressants, virulence factors, and genotoxins. RECENT FINDINGS: An expanding plethora of studies suggest and support the evidence of microbiome impacting cancer etiology. Several studies also indicate that the microbiome can supplement various cancer therapies, increasing their efficacy. The present review discusses the relationship between bacterial and viral microbiota with cancer, discussing different carcinogenic mechanisms influenced by prokaryotes with special emphasis on their immunomodulatory axis. It also elucidates the potential of the microbiome in transforming the efficacy of immunotherapeutic treatments. CONCLUSION: This review offers a thorough overview of the complex interaction between the human immune system and the microbiome and its impact on the development of cancer. The microbiome affects the immune responses as well as progression of tumor transformation, hence microbiome-based therapies can vastly improve the effectiveness of cancer immunotherapies. Individual variations of the microbiome and its dynamic variability in every individual impacts the immune modulation and cancer progression. Therefore, further research is required to understand these underlying processes in detail, so as to design better microbiome-immune system axis in the treatment of cancer.

Trends and determinants of tobacco use initiation in India: analysis of two rounds of the Global Adult Tobacco Survey.

OBJECTIVES: Early initiation of tobacco use can lead to lifelong addiction and increases tobacco-attributable morbidity and mortality. This study assesses trends in tobacco use initiation and factors associated with tobacco use initiation using disaggregated data from two rounds of the Global Adult Tobacco Survey India (GATS; 2009-2010 (GATS 1) and 2016-2017 (GATS 2)). DESIGN: Secondary analysis of repeated cross-sectional studies. SETTINGS AND PARTICIPANTS: The study involved data from 69 296 individuals and 76 069 households in GATS 1 and 74 037 individuals and 77 170 households in GATS 2, two rounds of a nationally representative survey in India. OUTCOME MEASURES: Mean age of initiation (as recalled by the participants) of smoked and smokeless tobacco (SLT) use (dependent variable) was compared and analysed across different sociodemographic variables (independent factors). We assessed change in mean age of initiation of tobacco usage on a daily basis between GATS 1 and GATS 2, and investigated the factors associated with early tobacco use initiation in the GATS 2 dataset (reported using adjusted ORs (aORs) with 95% CIs). RESULTS: The mean age of initiation of smoked tobacco and SLT in GATS 2 was 20.9±8.5 and 22.3±10.6 years, compared with 18.5±9.7 and 19.7±12.0 years in GATS 1. The mean age of initiation increased with age and among those who were better aware of the adverse effects of tobacco. As per GATS 2, males initiated smoked tobacco and SLT use earlier (20.6±7.4 and 21.7±9.1) than females (23.3±14.2 and 23.2±12.6 years). Younger participants (15-24 years) reported earlier initiation of SLT (15.5±4.2 years) compared with others. Binary logistic regression depicted variables associated with early initiation of tobacco. Awareness about the harms caused by tobacco affected the odds of SLT (aOR 1.4, 95% CI 1.3 to 1.7) and dual usage initiation (1.8, 1.6 to 2.0), but not of initiation of smoked tobacco products (1.1, 0.9 to 1.2). CONCLUSIONS: More robust health advocacy campaigns that communicate the harmful effects of tobacco on health could be useful to delay tobacco initiation, along with reducing the ease of access and affordability of tobacco products among vulnerable groups.

Interferon-expressing oncolytic adenovirus + chemoradiation inhibited pancreatic cancer growth in a hamster model.

Past clinical trials of adjuvant therapy combined with interferon (IFN) alpha, fluorouracil, cisplatin, and radiation improved the 5-year survival rate of pancreatic ductal adenocarcinoma (PDAC). However, these trials also revealed the disadvantages of the systemic toxicity of IFN and insufficient delivery of IFN. To improve efficacy and tolerability, we have developed an oncolytic adenovirus-expressing IFN (IFN-OAd). Here, we evaluated IFN-OAd in combination with chemotherapy (gemcitabine + nab-paclitaxel) + radiation. Combination index (CI) analysis showed that IFN-OAd + chemotherapy + radiation was synergistic (CI <1). Notably, IFN-OAd + chemotherapy + radiation remarkably suppressed tumor growth and induced a higher number of tumor-infiltrating lymphocytes without severe side toxic effects in an immunocompetent and adenovirus replication-permissive hamster PDAC model. This is the first study to report that gemcitabine + nab-paclitaxel, the current first-line chemotherapy for PDAC, did not hamper virus replication in a replication-permissive immunocompetent model. IFN-OAd has the potential to overcome the barriers to clinical application of IFN-based therapy through its tumor-specific expression of IFN, induction of antitumor immunity, and sensitization with chemoradiation. Combining IFN-OAd with gemcitabine + nab-paclitaxel + radiation might be an effective and clinically beneficial treatment for PDAC patients.

Awareness regarding the antitobacco laws and perceptions regarding interventions for effective tobacco control among young adults of Haryana, India.

Background: Tobacco is one of the major behavioral risk factors for noncommunicable diseases in India. Tobacco control depends on public awareness regarding prevalent antitobacco measures. Objectives: The present study documents the understanding of young adults (<25 years) regarding the antitobacco laws and their perception regarding interventions for effective tobacco control. Methods: A cross-sectional study was conducted in two districts of Haryana. A semistructured questionnaire was used to assess tobacco use, participants' awareness of sections 4, 5, 6 (a), and 8 of the Cigarette and Other Tobacco Products Act (COTPA, 2003), sources of information about antitobacco laws, and their implementation. The perception of participants about the effectiveness of laws and provisions was assessed using a three-point Likert scale. Results: Of the 1470 participants, 517 (35.2%) smoked or used smokeless products. They reported the media (84.6%) to be the most critical source of information about antitobacco laws, followed by the health department (57.6%) and family/peer group (44.9%). Most participants were aware of the prohibition of smoking in offices or banks, educational institutions, hospitals, and other public places. Both tobacco users and nonusers perceived health education programs to be an effective intervention to reduce tobacco use (P < 0.01). Conclusion: The awareness regarding COTPA has increased among the general population. The media could be a powerful tool to counteract the pro-tobacco cues in society. The need of the hour is to focus on improving compliance with antitobacco laws at the population level to achieve a tobacco-free India.

Higher baseline natural killer cell counts are associated with a lower 8-day blast count and lower day 33 minimal residual disease in children with pediatric B-acute lymphoblastic leukemia.

INTRODUCTION: Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Despite advancements in treatment, a significant proportion of children relapse. Recently, immunotherapy has gained momentum and is becoming popular, especially for relapsed and refractory cases. NK cells are an important part of tumor immunity and are involved in the direct killing of tumor cells. Their role in B-ALL has not been explored. Therefore, this study was conducted to correlate the number of NK cells with standard prognostic parameters in B-ALL. METHODS: 25 subjects with newly diagnosed B-ALL between 0-14 years were recruited for the study from Pediatric OPD or emergency of the hospital. Along with a complete hemogram and peripheral smear examination, immunophenotyping by flow cytometry was done at the time of diagnosis for NK cell enumeration. The number of NK cells was correlated with standard prognostic parameters using the spearman correlation coefficient. RESULTS: Baseline NK cell percentage demonstrated a significant negative correlation with Prednisone poor day 8 blast response (P value = 0.02, r value = -0.44) and positive MRD (P value = 0.01, r value = -0.49) at day 33. A negative correlation was also noticed between NK cell percentage and unfavorable cytogenetics (hypodiploidy), although it was not significant (P value = 0.06, r value = -0.38). The number of NK cells did not correlate with age, gender and WBC count. Therefore, evaluating NK cells at diagnosis may serve as a simple and useful parameter for prognostication and risk stratification. CONCLUSION: It may be assumed that a higher percentage of NK cells is associated with improved outcomes and probably a better prognosis. NK numbers may serve as an early independent parameter predicting prognosis and survival in children with B-ALL, thus helping to decide individual therapeutic regimens.

Neutron Activation Analysis: An Excellent Nondestructive Analytical Technique for Trace Metal Analysis.

For proper functioning of the human body, several metals are required in different concentrations but if their concentration slightly elevates, because of any metal-contaminated environment or of other food sources, which leads to high toxicity and different chronic health issues. Different analytical techniques like atomic absorption spectroscopy, X-ray fluorescence, inductively coupled plasma- mass spectroscopy (ICP-MS) and flame atomic absorption spectroscopy are used for metals analysis present in different samples in different fields but nowadays neutron activation analysis (NAA) is preferred over other analytical techniques because it is an efficient, multi-elemental, nondestructive analytical technique having an ultralow minimum detection limit, therefore it can detect heavy metals (HMs) even if at a very trace level parts per billion (ppb) with a quite simple sample preparation technique. This technique is known as "referee technique" because of its accuracy and trustworthiness. There is a widespread use of this technique in biomedical science like in Alzheimer's disease, cancer, arthritis, metabolism study, brain tumor and in many more conditions where metals are actively present. For its typical sample sizes and due to a multitude of additional benefits, it also helps in mapping of pathophysiology of the disease. Besides all, mainly in biomedical science the biological samples can easily be analyzed irrespective of any form. In recent years NAA is preferred over other analytical techniques in several research fields, so this article focuses on the analytical technique, its general principle and recent applications.

Minor tropical fruits as a potential source of bioactive and functional foods.

Tropical fruits are defined as fruits that are grown in hot and humid regions within the Tropic of Cancer and Tropic of Capricorn, covering most of the tropical and subtropical areas of Asia, Africa, Central America, South America, the Caribbean and Oceania. Depending on the cultivation area covered, economic value and popularity these tropical fruits are divided into major and minor tropical fruits. There is an annual increment of 3.8% in terms of commercialization of the tropical fruits. In total 26 minor tropical fruits (Kiwifruit, Lutqua, Carambola, Tree Tomato, Elephant apple, Rambutan, Bay berry, Mangosteen, Bhawa, Loquat, Silver berry, Durian, Persimon, Longan, Passion fruit, Water apple, Pulasan, Indian gooseberry, Guava, Lychee, Annona, Pitaya, Sapodilla, Pepino, Jaboticaba, Jackfruit) have been covered in this work. The nutritional composition, phytochemical composition, health benefits, traditional use of these minor tropical fruits and their role in food fortification have been portrayed.

Evolution of tobacco control in India: a narrative review of the legislative and regulatory approach.

Tobacco is the only consumer product that kills half its users yearly. The challenges posed by tobacco control are limitless especially in a country like India where in addition to smoked forms, other smokeless forms of tobacco are also highly prevalent. Apart from being a health hazard tobacco is also a great environmental hazard. Policies for controlling tobacco use also include policy to prevent people from second hand smoke, which is aimed at improvement of air quality. According to the National Non-Communicable Disease Monitoring Survey, 2017-18, daily tobacco use was 32.8% in adults (18-69 years) and 3.1% in adolescents (15-17 years). Overall reduction in tobacco users by 8.1 Million was seen from GATS-1 to GATS-2, and prevalence amongst youth decreased from 18.4 to 12.4%. GYTS-4 (2019) revealed that 8.5% of students, 9.6% of boys and 7.4% of girls-currently used any tobacco products. This makes tobacco control a priority in India. Tobacco control consists of different approaches such as educational, healthcare, legislative, regulatory and fiscal. In the present article we traverse nearly five decades and decode the evolution of legislative, regulatory and fiscal approaches to Tobacco Control in India. A critical evaluation of all these approaches is described in the format of the MPOWER strategy for Tobacco Control which stands for Monitoring Tobacco use, Preventing people from Second Hand Smoke, Offering help to quit, Waring regarding ill effects of tobacco, Enforcing bans and Raising taxes on tobacco products.

Minnelide synergizes with conventional chemotherapy by targeting both cancer and associated stroma components in pancreatic cancer.

Addition of nab-paclitaxel to gemcitabine offers a survival benefit of only 6 weeks over gemcitabine alone at a cost of increased toxicity in PDAC. The goal of the present study is to evaluate the efficacy of Minnelide, a water-soluble prodrug of triptolide, in combination with the standard of care regimen for chemotherapy with the added advantage of reducing the doses of these drugs to minimize toxicity. Pancreatic cancer cell lines were implanted subcutaneously or orthotopically in athymic nude or C57BL/6J mice. Subsequently, animals were randomized and received saline or minnelide or full dose chemotherapy or low dose chemotherapy or minnelide in combination with low dose chemotherapy. Our results show that a combination of low doses of Minnelide with Gemcitabine + nab-paclitaxel significantly inhibited tumor progression and increased the survival of tumor-bearing mice in comparison with conventional chemotherapy alone. Moreover, combination therapy significantly reduced cancer-related morbidity by decreasing ascites and metastasis and effectively targeted both cancer and the associated stroma. In vitro studies with a combination of low doses of triptolide and paclitaxel significantly decreased the cell viability, increased apoptosis and led to significantly increased M-phase cell cycle arrest in various pancreatic cancer cell lines as compared to either drug alone. Our results show that Minnelide synergizes with conventional chemotherapy leading to a significant reduction in the doses of these toxic drugs, all the while achieving better efficacy in the treatment of PDAC. This combination effectively targeted both the cancer and the associated stromal components of pancreatic cancer.

Targeting nanoparticles to malignant tumors.

Nanomaterials are at the forefront of health research and development. Among different nanomaterials, nanoparticles are especially promising for cancer theranostics. However, despite great potential, the clinical translation of nano-based applications continues to face obstacles. A major hurdle to the localized eradication of tumors is the efficient targeting of nanomaterials to the desired tissues and cells. In particular, nanoparticle properties and the route of administration impact the efficacy of precision nanomedicine. This review focuses on nanoparticles that have been produced for the detection and treatment of cancer. Common and tissue-specific barriers that limit the accumulation of nanoparticles in malignant tumors are discussed. The in-depth discussion focuses on the physicochemical properties of nanoparticles and the surface modifications that achieve efficient accumulation at tumor sites. Furthermore, limitations of current strategies and open questions are presented. The review concludes with an outlook on future directions and the trajectories that will drive the field forward to advance nano-oncology in the clinic.

Hypoxia-Driven Oncometabolite L-2HG Maintains Stemness-Differentiation Balance and Facilitates Immune Evasion in Pancreatic Cancer.

In pancreatic cancer, the robust fibroinflammatory stroma contributes to immune suppression and renders tumors hypoxic, altering intratumoral metabolic pathways and leading to poor survival. One metabolic enzyme activated during hypoxia is lactate dehydrogenase A (LDHA). As a result of its promiscuous activity under hypoxia, LDHA produces L-2 hydroxyglutarate (L-2HG), an epigenetic modifier, that regulates the tumor transcriptome. However, the role of L-2HG in remodeling the pancreatic tumor microenvironment is not known. Here we used mass spectrometry to detect L-2HG in serum samples from patients with pancreatic cancer, comprising tumor cells as well as stromal cells. Both hypoxic pancreatic tumors as well as serum from patients with pancreatic cancer accumulated L-2HG as a result of promiscuous activity of LDHA. This abnormally accumulated L-2HG led to H3 hypermethylation and altered gene expression, which regulated a critical balance between stemness and differentiation in pancreatic tumors. Secreted L-2HG inhibited T-cell proliferation and migration, suppressing antitumor immunity. In a syngeneic orthotopic model of pancreatic cancer, inhibition of LDH with GSK2837808A decreased L-2HG, induced tumor regression, and sensitized tumors to anti-PD1 therapy. In conclusion, hypoxia-mediated promiscuous activity of LDH produces L-2HG in pancreatic tumor cells, regulating the stemness-differentiation balance and contributing to immune evasion. Targeting LDH can be developed as a potential therapy to sensitize pancreatic tumors to checkpoint inhibitor therapy. SIGNIFICANCE: This study shows that promiscuous LDH activity produces L-2HG in pancreatic tumor and stromal cells, modulating tumor stemness and immune cell function and infiltration in the tumor microenvironment.

PGMD/curcumin nanoparticles for the treatment of breast cancer.

The present study aims at developing PGMD (poly-glycerol-malic acid-dodecanedioic acid)/curcumin nanoparticles based formulation for anticancer activity against breast cancer cells. The nanoparticles were prepared using both the variants of PGMD polymer (PGMD 7:3 and PGMD 6:4) with curcumin (i.e. CUR NP 7:3 and CUR NP 6:4). The size of CUR NP 7:3 and CUR NP 6:4 were found to be ~ 110 and 218 nm with a polydispersity index of 0.174 and 0.36, respectively. Further, the zeta potential of the particles was - 18.9 and - 17.5 mV for CUR NP 7:3 and CUR NP 6:4, respectively. The entrapment efficiency of both the nanoparticles was in the range of 75-81%. In vitro anticancer activity and the scratch assay were conducted on breast cancer cell lines, MCF-7 and MDA-MB-231. The IC50 of the nanoformulations was observed to be 40.2 and 33.6 µM at 48 h for CUR NP 7:3 and CUR NP 6:4, respectively, in MCF-7 cell line; for MDA-MB-231 it was 43.4 and 30.5 µM. Acridine orange/EtBr and DAPI staining assays showed apoptotic features and nuclear anomalies in the treated cells. This was further confirmed by western blot analysis that showed overexpression of caspase 9 indicating curcumin role in apoptosis.

Diosgenin Loaded Polymeric Nanoparticles with Potential Anticancer Efficacy.

This study aims to determine the anticancer efficacy of diosgenin encapsulated poly-glycerol malate co-dodecanedioate (PGMD) nanoparticles. Diosgenin loaded PGMD nanoparticles (variants 7:3 and 6:4) were synthesized by the nanoprecipitation method. The synthesis of PGMD nanoparticles was systematically optimized employing the Box-Behnken design and taking into account the influence of various independent variables such as concentrations of each PGMD, diosgenin and PF-68 on the responses such as size and PDI of the particles. Mathematical modeling was done using the Quadratic second order modeling method and response surface analysis was undertaken to elucidate the factor-response relationship. The obtained size of PGMD 7:3 and PGMD 6:4 nanoparticles were 133.6 nm and 121.4 nm, respectively, as measured through dynamic light scattering (DLS). The entrapment efficiency was in the range of 77-83%. The in vitro drug release studies showed diffusion and dissolution controlled drug release pattern following Korsmeyer-Peppas kinetic model. Furthermore, in vitro morphological and cytotoxic studies were performed to evaluate the toxicity of synthesized drug loaded nanoparticles in model cell lines. The IC50 after 48 h was observed to be 27.14 µM, 15.15 µM and 13.91 µM for free diosgenin, PGMD 7:3 and PGMD 6:4 nanoparticles, respectively, when administered in A549 lung carcinoma cell lines.

Stroma secreted IL6 selects for "stem-like" population and alters pancreatic tumor microenvironment by reprogramming metabolic pathways.

Pancreatic adenocarcinoma is a devastating disease with an abysmal survival rate of 9%. A robust fibro-inflammatory and desmoplastic stroma, characteristic of pancreatic cancer, contribute to the challenges in developing viable therapeutic strategies in this disease. Apart from constricting blood vessels and preventing efficient drug delivery to the tumor, the stroma also contributes to the aggressive biology of cancer along with its immune-evasive microenvironment. In this study, we show that in pancreatic tumors, the developing stroma increases tumor initiation frequency in pancreatic cancer cells in vivo by enriching for CD133 + aggressive "stem-like" cells. Additionally, the stromal fibroblasts secrete IL6 as the major cytokine, increases glycolytic flux in the pancreatic tumor cells, and increases lactate efflux in the microenvironment via activation of the STAT signaling pathway. We also show that the secreted lactate favors activation of M2 macrophages in the tumor microenvironment, which excludes CD8 + T cells in the tumor. Our data additionally confirms that the treatment of pancreatic tumors with anti-IL6 antibody results in tumor regression as well as decreased CD133 + population within the tumor. Furthermore, inhibiting the lactate efflux in the microenvironment reduces M2 macrophages, and makes pancreatic tumors more responsive to anti-PD1 therapy. This suggests that stromal IL6 driven metabolic reprogramming plays a significant role in the development of an immune-evasive microenvironment. In conclusion, our study shows that targeting the metabolic pathways affected by stromal IL6 can make pancreatic tumors amenable to checkpoint inhibitor therapy.

Poly-(Lactic-co-Glycolic) Acid Nanoparticles for Synergistic Delivery of Epirubicin and Paclitaxel to Human Lung Cancer Cells.

Combination therapy using chemically distinct drugs has appeared as one of the promising strategies to improve anticancer treatment efficiency. In the present investigation, poly-(lactic-co-glycolic) acid (PLGA) nanoparticles electrostatically conjugated with polyethylenimine (PEI)-based co-delivery system for epirubicin and paclitaxel (PLGA-PEI-EPI-PTX NPs) has been developed. The PLGA-PEI-EPI-PTX NPs exhibited a monodispersed size distribution with an average size of 240.93 ± 12.70 nm as measured through DLS and 70.8-145 nm using AFM. The zeta potential of 41.95 ± 0.65 mV from -17.45 ± 2.15 mV further confirmed the colloidal stability and PEI modification on PLGA nanoparticles. Encapsulation and loading efficiency along with in vitro release of drug for nanoparticles were done spectrophotometrically. The FTIR analysis of PLGA-PEI-EPI-PTX NPs revealed the involvement of amide moiety between polymer PLGA and PEI. The effect of nanoparticles on the cell migration was also corroborated through wound healing assay. The MTT assay demonstrated that PLGA-PEI-EPI-PTX NPs exhibited considerable anticancer potential as compared to the naïve drugs. Further, p53 protein expression analysed through western blot showed enhanced expression. This study suggests that combination therapy using PLGA-PEI-EPI-PTX NPs represent a potential approach and could offer clinical benefits in the future for lung cancer patients.

Study of internet addiction and its association with depression and insomnia in university students.

INTRODUCTION: Use of internet has increased exponentially worldwide with prevalence of internet addiction ranging from 1.6% to 18 % or even higher. Depression and insomnia has been linked with internet addiction and overuse in several studies. AIMS AND OBJECTIVES: Present study has looked in to pattern and prevalence of internet addiction in university students. This study has also explored the association of internet addiction with depression and insomnia. MATERIAL AND METHODS: In this cross sectional study 954 subjects were enrolled who had been using internet for past 6 months. Information regarding pattern of use and socio demographic characteristics were recorded. Internet addiction Test (IAT), PHQ-9,and insomnia Severity Index (ISI) were applied to measure internet addiction, depression and insomnia respectively. RESULTS: Among 954 subjects, 518 (60.59%) were male and 376 (39.41%) were female with mean age of 23.81 (SD ± 3.72). 15.51% study subjects were internet addicts and 49.19% were over users. Several parameters including graduation level, time spent per day on line, place of internet use, smoking and alcohol had significant association with internet addiction. Internet addiction was predominantly associated with depression and insomnia. CONCLUSION: Internet addiction is a rising concern among youth. Several parameters including gender, time spent on line, alcohol, smoking predicts higher risk of internet addiction. Depression and insomnia are more common in internet addicts and overusers.

Oncolytic Adenoviruses: Strategies for Improved Targeting and Specificity.

Cancer is a major health problem. Most of the treatments exhibit systemic toxicity, as they are not targeted or specific to cancerous cells and tumors. Adenoviruses are very promising gene delivery vectors and have immense potential to deliver targeted therapy. Here, we review a wide range of strategies that have been tried, tested, and demonstrated to enhance the specificity of oncolytic viruses towards specific cancer cells. A combination of these strategies and other conventional therapies may be more effective than any of those strategies alone.

Effectiveness of a culturally appropriate nutrition educational intervention delivered through health services to improve growth and complementary feeding of infants: A quasi-experimental study from Chandigarh, India.

BACKGROUND: Malnutrition is a major public health problem in India, especially among urban poor children. The objective of the study was to determine the effectiveness of a culturally appropriate nutrition educational intervention that can be delivered through health services and digitized child undernutrition tracking module for health workers to improve complementary feeding of infants of age six months to 12 months in Chandigarh, North India, to prevent malnutrition in infants. METHODS: A quasi-experimental study was conducted in a non-randomized intervention (Burail) and control area (Maloya) among a vulnerable population in Chandigarh, North India. The mother-infant dyads (MIDs) in the intervention group(n = 202) received culturally appropriate nutrition educational intervention, were supported individually by trained health workers in infant feeding and followed up for six months. Health workers were monitored through a digitized tracking module. The MIDs in the control group (n = 202) received routine care under the national health program. The mean (±S.D.) age of infants in the intervention and control group was 5.4 (±0.8) months and 5.5 (±0.7) months, respectively. The data was collected using a pre-tested semi-structured questionnaire and anthropometry of infants at baseline and end line. The primary outcome was a mean change in weight. The effectiveness of the intervention was measured by conducting the difference in difference (DID) analysis in mean change in weight between intervention and control group. RESULT: At baseline, the mean (±S.D.) weight of infants was 6.6(±0.64) kg and 6.6 (±0.52) kg in the intervention and control group. The mean (±S.D.) length of infants was 64.3 (±2.0) cm in the intervention group and 65.1 (±1.7) cm in the control group. Out of 404, 190 and 191 MIDs in the intervention and control group completed the study, respectively. A significantly higher number of infants in the intervention group were started on complementary feeding at six months of age (72.6% versus45.5%, p<0.01) and received foods having thick consistency (82.1% versus 41.9%, p<-0.01). There was significant weight gain in intervention group infants (DID means = 0.27 kg, p<0.01) and length gain (DID means = 0.9 cm, p<0.01) from the baseline. Also, there was significant decline in the proportion of undernourished (10% versus18.8%, OR = 0.47, p = 0.01) and wasted infants (7.3% versus15.7%, OR = 0.42, p = 0.01) in the intervention group. CONCLUSION: Community-based nutrition educational intervention delivered through the routine health services and digitized tracking of malnourished children can effectively improve the complementary feeding and growth of children six months to one year among vulnerable populations.

Targeting tumor-intrinsic hexosamine biosynthesis sensitizes pancreatic cancer to anti-PD1 therapy.

Pancreatic ductal adenocarcinoma (PDAC) is considered to be a highly immunosuppressive and heterogenous neoplasm. Despite improved knowledge regarding the genetic background of the tumor and better understanding of the tumor microenvironment, immune checkpoint inhibitor therapy (targeting CTLA4, PD1, PDL1) has not been very successful against PDAC. The robust desmoplastic stroma, along with an extensive extracellular matrix (ECM) that is rich in hyaluronan, plays an integral role in this immune evasion. Hexosamine biosynthesis pathway (HBP), a shunt pathway of glycolysis, is a metabolic node in cancer cells that can promote survival pathways on the one hand and influence the hyaluronan synthesis in the ECM on the other. The rate-limiting enzyme of the pathway, glutamine-fructose amidotransferase 1 (GFAT1), uses glutamine and fructose 6-phosphate to eventually synthesize uridine diphosphate N-acetylglucosamine (UDP-GlcNAc). In the current manuscript, we targeted this glutamine-utilizing enzyme by a small molecule glutamine analog (6-diazo-5-oxo-l-norleucine [DON]). Our results showed that DON decreased the self-renewal potential and metastatic ability of tumor cells. Further, treatment with DON decreased hyaluronan and collagen in the tumor microenvironment, leading to an extensive remodeling of the ECM and an increased infiltration of CD8+ T cells. Additionally, treatment with DON sensitized pancreatic tumors to anti-PD1 therapy, resulting in tumor regression and prolonged survival.