scholarly journals Nutritional Immunity, Zinc Sufficiency, and COVID-19 Mortality in Socially Similar European Populations

2021 ◽  
Vol 12 ◽  
Author(s):  
Samer Singh ◽  
Amita Diwaker ◽  
Brijesh P. Singh ◽  
Rakesh K. Singh
Keyword(s):  
Standard Of Care ◽  
Protective Role ◽  
Vulnerable Groups ◽  
P Value ◽  
Negative Effects ◽  
Nutritional Immunity ◽  
Incidence And Mortality ◽  
Standard Of Care Treatment ◽  
The Impact ◽  
European Populations

The impact of zinc (Zn) sufficiency/supplementation on COVID-19-associated mortality and incidence (SARS-CoV-2 infections) remains unknown. During an infection, the levels of free Zn are reduced as part of “nutritional immunity” to limit the growth and replication of pathogen and the ensuing inflammatory damage. Considering its key role in immune competency and frequently recorded deficiency in large sections of different populations, Zn has been prescribed for both prophylactic and therapeutic purposes in COVID-19 without any corroborating evidence for its protective role. Multiple trials are underway evaluating the effect of Zn supplementation on COVID-19 outcome in patients getting standard of care treatment. However, the trial designs presumably lack the power to identify negative effects of Zn supplementation, especially in the vulnerable groups of elderly and patients with comorbidities (contributing 9 out of 10 deaths; up to >8,000-fold higher mortality). In this study, we have analyzed COVID-19 mortality and incidence (case) data from 23 socially similar European populations with comparable confounders (population: 522.47 million; experiencing up to >150-fold difference in death rates) and at the matching stage of the pandemic (March 12 to June 26, 2020; first wave of COVID-19 incidence and mortality). Our results suggest a positive correlation between populations’ Zn-sufficiency status and COVID-19 mortality [r (23): 0.7893–0.6849, p-value < 0.0003] as well as incidence [r (23):0.8084–0.5658; p-value < 0.005]. The observed association is contrary to what would be expected if Zn sufficiency was protective in COVID-19. Thus, controlled trials or retrospective analyses of the adverse event patients’ data should be undertaken to correctly guide the practice of Zn supplementation in COVID-19.

The Impact of L-Carnitine and Coenzyme Q10 as Protection Against Busulfan-Oxidative Stress in the Liver of Adult Rats

2020 ◽  
Vol 10 (5) ◽  
pp. 578-586
Author(s):  
Areeg M. Abdelrazek ◽  
Shimaa A. Haredy
Keyword(s):  
Oxidative Stress ◽  
Coenzyme Q10 ◽  
Protective Role ◽  
Albino Rats ◽  
Distilled Water ◽  
Negative Effects ◽  
Adult Rats ◽  
Stress Damage ◽  
The Impact ◽  
Liver Tissues

Background: Busulfan (Bu) is an anticancer drug with a variety of adverse effects for cancer patients. Oxidative stress has been considered as a common pathological mechanism and it has a key role in the initiation and progression of liver injury by Bu. Aim: The study aimed to evaluate the antioxidant impact of L-Carnitine and Coenzyme Q10 and their protective role against oxidative stress damage in liver tissues. Methods and Material: Thirty-six albino rats were divided equally into six groups. G1 (con), received I.P. injection of DMSO plus 1 ml of distilled water daily by oral gavages; G2 (Bu), received I.P. injection of Bu plus 1 ml of the distilled water daily; G3 (L-Car), received 1 ml of L-Car orally; G4 (Bu + L-Car) received I.P. injection of Bu plus 1 ml of L-Car, G5 (CoQ10) 1 ml of CoQ10 daily; and G6 (Bu + CoQ10) received I.P. injection of Bu plus 1 ml of CoQ10 daily. Results: The recent data showed that Bu induced significant (P<0.05) elevation in serum ALT, AST, liver GSSG, NO, MDA and 8-OHDG, while showing significant (P<0.05) decrease in liver GSH and ATP. On the other hand, L-Carnitine and Coenzyme Q10 ameliorated the negative effects prompted by Bu. Immunohistochemical expression of caspase-3 in liver tissues reported pathological alterations in Bu group while also showed significant recovery in L-Car more than CoQ10. Conclusion: L-Car, as well as CoQ10, can enhance the hepatotoxic effects of Bu by promoting energy production in oxidative phosphorylation process and by scavenging the free radicals.

scholarly journals STEM-24. RADIATION-INDUCED EXTRACELLULAR VESICLE (EV) RELEASE OF miR-603 PROMOTES IGF1-MEDIATED STEM CALL STATE IN GLIOBLASTOMAS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii201-ii201
Author(s):  
Valya Ramakrishnan ◽  
Beibei Xu ◽  
Johnny Akers ◽  
Thien Nguyen ◽  
Jun Ma ◽  
...  
Keyword(s):  
Recipient Cell ◽  
Alkylating Agents ◽  
Acquired Resistance ◽  
Standard Of Care ◽  
Extracellular Vesicle ◽  
Cross Resistance ◽  
Dna Damages ◽  
Care Treatment ◽  
Standard Of Care Treatment ◽  
The Impact

Abstract INTRODUCTION Release of exosomes and extracellular vesicles (EV) by glioblastomas plays key roles in modulating the tumor microenvironment and therapeutic response. Studies to date have largely focused on the impact of EV and exosomes on the recipient cell. Here, we demonstrate that EV-mediated export of a master-regulatory miRNA has fate-determining impacts on the cell releasing the EVs. METHODS microRNA (miRNA) profiling was performed using clinical glioblastoma specimens from the same patients derived pre- and post-standard of care treatment. Mechanism mediating altered miRNA homeostasis were assessed. RESULTS While the levels of nearly all miRNAs remained unchanged after standard-of-care treatment, decreased levels of few, select miRNAs were observed, including miR-603. In response to ionizing radiation (IR), but not temozolomide (TMZ), glioblastoma cell lines exhibited a time-dependent decrease in miR-603 levels. While miR-603 biogenesis and degradation remained unchanged after IR, IR induced an increase in EV-mediated export of miR-603. Profiling of miR-603 targets revealed that miR-603 repressed the insulin-like growth factor 1 (IGF1) and IGF1 receptor (IGF1R), genes required to maintain the cancer stem cell (CSC) state, as well as MGMT, the gene encoding a DNA repair protein that detoxifies temozolomide (TMZ) induced DNA damages. IR induced export of miR-603 de-repress IGF1/IGF1R to promote radiation resistance and de-repress MGMT to promote cross-resistance to TMZ and CCNU. Ectopic miR-603 expression overwhelmed cellular capacity for miR-603 export and synergized with the tumoricidal effects of IR and temozolomide (TMZ). CONCLUSIONS Radiation stimulated EV-mediated export of miR-603 to facilitate acquired resistance to IR and cross-resistance to DNA alkylating agents.

Tabletop Tsunami Simulator In Tsunami Disaster Preparation To Make Schools Of Disaster Preparedness

2021 ◽  
Vol 9 (1) ◽  
pp. 55-59
Author(s):  
Feri Ekaprasetia ◽  
Guruh Wirasakti
Keyword(s):  
Primary School ◽  
Vulnerable Groups ◽  
P Value ◽  
Attitude Score ◽  
Whitney Test ◽  
Tsunami Disaster ◽  
Knowledge And Attitudes ◽  
Mann Whitney Test ◽  
Post Test ◽  
The Impact

Introduction: Tsunami in Indonesia become a threat to society, especially for vulnerable groups. Primary school students are one of the vulnerable groups that should have adequate preparedness both in their knowledge and attitudes in facing the tsunami. To support the preparedness, a tabletop tsunami simulator has been developed. Objective: To describe the tsunami preparedness of school-age children and to assess the impact of the tabletop tsunami simulator on the knowledge and attitudes of school children towards tsunamis. Methods: The study design was a one group pre-test – post-test design with a total participant of 157 students. The research instrument used was a tabletop tsunami simulator and a questionnaire to assess knowledge and attitude towards tsunamis. The statistical test used was the Mann Whitney test. The inclusion criteria included primary school 5th and 6th grade students, had a smartphone, and were willing to be participants. The data was collected using Google form and had obtained ethical approval number 62/SDS/KEPK/TL/VI/2020. Result: The Mann Whitney test showed a significant effect between the tabletop tsunami simulator and the participants’ knowledge of tsunamis with a p-value of 0.000 (p-value <0.05). In the attitude variable, an increase in the attitude score between the pre-test and post-test was also observed. The average attitude score increased from 32.99 to 34.97, with a p-value = 0.000. Conclusion: There is a significant effect between the tabletop tsunami simulator with the participants’ knowledge and attitudes in facing the threat of a tsunami.

Use of placebo in cancer medicine: The experience of a National Clinical Trials organization

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6104-6104
Author(s):  
J. L. Pater ◽  
W. Parulekar
Keyword(s):  
Clinical Trials ◽  
Supportive Care ◽  
Study Design ◽  
Standard Of Care ◽  
Phase Iii ◽  
Design Data ◽  
Standard Of Care Treatment ◽  
Prevention Trials ◽  
The Impact ◽  
Phase Iii Studies

6104 Background: The use of placebos in cancer clinical trials requires careful evaluation. Factors that must be considered include the impact of placebo on endpoint measurement, the efficacy of placebo relative to standard of care treatment, patient altruism/acceptance of a non-active intervention and the resulting increase in complexity of study conduct with respect to randomization, drug supply, data management, analysis and the unblinding process. Methods: We reviewed the experience of the National Cancer Institute of Canada Clinical Trials Group with the use of placebo in the randomized phase III setting from 1982–2005. Results: Since 1982, 34 studies were identified that utilized a placebo as part of study design. Data is presented below according to the type of study and date of study activation. The numbers in brackets represent those studies in which placebo was used alone in the control arm. Supportive care studies were the most common type of study employing a placebo as part of study design and constituted almost 50% of our Group’s experience. Therapeutic studies involving placebo were conducted in multiple sites including breast (4), lung (6), myeloma (1), melanoma (1), ovary (1) and pancreas (1). Conclusion: Phase III studies involving a placebo constitute an important part of our clinical trial activity and cross the spectrum of supportive care, therapeutic and prevention trials. The use of placebo in cancer studies may increase due to the relative ease of blinding in studies that evaluate targeted, oral therapies with minimal toxicities as well as the need for unbiased assessment of increasingly used endpoints such as time to progression. [Table: see text] No significant financial relationships to disclose.

The AIM-HN and SEQ-HN study: A pivotal study evaluating the efficacy of tipifarnib in patients with head and neck squamous cell carcinoma (HNSCC) with hras mutations (AIM-HN) and the impact of hras mutations on response to first line systemic therapies for HNSCC (SEQ-HN).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS6593-TPS6593
Author(s):  
Robert I. Haddad ◽  
Kevin Joseph Harrington ◽  
Lisa F. Licitra ◽  
Amanda Psyrri ◽  
Nabil F. Saba ◽  
...  
Keyword(s):  
Final Analysis ◽  
Standard Of Care ◽  
Patient Characteristics ◽  
Unknown Primary ◽  
Missense Mutations ◽  
First Line ◽  
Open Label ◽  
Significance Level ◽  
Standard Of Care Treatment ◽  
The Impact

TPS6593 Background: HRAS mutations define a unique molecular subset of ~ 5% of HNSCC. Evidence suggests that these tumors respond poorly to standard systemic therapy but the impact of HRAS missense mutations on clinical outcomes has not been formally characterized. Tipifarnib is a potent and selective inhibitor of farnesyltransferase, a critical enzyme for HRAS activity. Phase 2 Proof of concept for tipifarnib in HRAS mutant HNSCC was recently achieved in study KO-TIP-001 (NCT02383927, Ho et. al. ESMO 2018). Methods: The AIM-HN and SEQ-HN Study (KO-TIP-007, NCT03719690) is an ongoing international, multicenter, open-label, 2 cohort (AIM-HN and SEQ-HN), pivotal trial designed to determine the Overall Response Rate (ORR) of tipifarnib in patients (pts) with HRAS mutant HNSCC (AIM-HN). SEQ-HN will retrospectively investigate how the ORR to first line treatment compares between the accrued HRAS mutant pts to matched-case control HRAS wild type (wt) HNSCC pts. Information on subsequent lines of therapy for HRAS mutant and wt pts will also be collected. AIM-HN will enroll at least 59 pts (oral cavity, pharynx, larynx, sinonasal, nasopharyngeal, or unknown primary) who are refractory or have relapsed from at least one prior line of systemic platinum-based therapy and have measurable disease by RECIST 1.1. AIM-HN pts must have tumors with >35% HRAS mutant variant allele frequency (VAF) or >20% VAF if serum albumin is >3.5 g/l. AIM-HN pts will receive treatment with tipifarnib at 600 mg bid on days 1-7 and 14-21 of 28-day cycles. Using Simon's Two-Stage Minimax design, if true ORR is > 30%, the study will have 80% power to detect ORR > 15% at 0.025 significance level. Both interim (after first 31 pts) and final analysis, 2-sided 95% CI on ORR, will be performed on the modified intent to treat population. The SEQ-HN observational cohort will enroll ~225 control pts who will receive standard of care treatment. A subset of SEQ-HN pts will be matched to the HRAS mutant AIM-HN pts according to defined patient characteristics and compared for responses to therapy. Clinical trial information: NCT02383927 .

scholarly journals Effects of Covid-19 lockdown on mental health and sleep disturbances, results from an Italian survey

2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
G Voglino ◽  
M R Gualano ◽  
G Lo Moro ◽  
F Bert ◽  
R Siliquini
Keyword(s):  
Mental Health ◽  
Chronic Conditions ◽  
Sleep Disturbances ◽  
Peer Pressure ◽  
Anxiety Symptoms ◽  
Vulnerable Groups ◽  
P Value ◽  
Italian Population ◽  
High Prevalence ◽  
The Impact

Abstract Background The Covid-19 pandemic is affecting different aspects of our society and brand-new conditions are expected after the lockdown. Italy was the first European country that entered a nationwide lockdown during the COVID-19 pandemic. Since quarantine can impact on mental health, this study aimed to estimate the prevalence of depressive symptoms, anxiety symptoms and sleeping disturbances in the Italian population during lockdown. The factors that might influence such outcomes were explored. Methods The COvid COllateral ImpactS (COCOS) project was a national cross-sectional survey performed during the last 14 days of the Italian lockdown. Questionnaires were online and included items on socio-demographics, behaviours, and healthcare access. Depression was assessed through the Patient Health Questionnaire-2, anxiety through the Generalized Anxiety Disorder-2. Participants referring sleep disturbances completed the Insomnia Severity Index. Descriptive analyses, univariable and multivariable logistic regressions were performed (p-value&lt;0.05 significant). Results The sample size was 1515. Females were 65.6%, and the median age was 42 years (IQR=23). Depression and anxiety symptoms prevalence were 24.7% and 23.2%. The 42.2% had sleep disturbances and, among them, 17.4% reported moderate/severe insomnia. Being female, increased time spent on internet, and avoidance of activities for peer pressure increased the likelihood of at least one of mental health outcomes. Increasing age, not experiencing work-related troubles, being married/cohabitant reduced such probability. Females and participants with chronic conditions resulted positively associated with sleep disturbances. Conclusions The results showed a high prevalence of mental health issues. Since the impact might be long-lasting, it is crucial to study effective interventions, specifically planning strategies for more vulnerable groups, e.g. youths, and considering the role of internet. Key messages A high prevalence of mental issues and sleep disturbances was recorded during the last week of the lockdown. Age, gender, marital status and the time spent on internet affected mental health while gender and presence of chronic conditions were predictors of sleep disturbances.

scholarly journals Calcitriol Suppression of Parathyroid Hormone Fails to Improve Skeletal Properties in an Animal Model of Chronic Kidney Disease

2016 ◽  
Vol 43 (1) ◽  
pp. 20-31 ◽  
Author(s):  
Christopher L. Newman ◽  
Nannan Tian ◽  
Max A. Hammond ◽  
Joseph M. Wallace ◽  
Drew M. Brown ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Chronic Kidney Disease ◽  
Parathyroid Hormone ◽  
Kidney Disease ◽  
Mineral Metabolism ◽  
Standard Of Care ◽  
Negative Effects ◽  
Increased Risk ◽  
The Impact ◽  
Normal Controls

Background: Chronic kidney disease (CKD) leads to complex metabolic changes and an increased risk of fracture. Currently, calcitriol is the standard of care as it effectively suppresses parathyroid hormone (PTH) levels in CKD patients. While calcitriol and its analogs improve BMD and reduce fractures in the general population, the extension of these benefits to patients with advanced kidney disease is unclear. Here, the impact of calcitriol on the skeleton was examined in the setting of reduction in PTH. Methods: Male Cy/+ rats, a PKD-like CKD model, were treated with either vehicle or calcitriol for 5 weeks. Their normal littermates served as controls. Animals were assessed for changes in mineral metabolism and skeletal parameters (microCT, histology, whole bone mechanics and bone quality). Results: PTH levels were significantly higher (12-fold) in animals with CKD compared to normal controls. CKD animals also exhibited negative changes in bone structural and mechanical properties. Calcitriol treatment resulted in a 60% suppression of PTH levels in animals with CKD. Despite these changes, it had no impact on bone volume (cortical or cancellous), bone turnover, osteoclast number or whole bone mechanical properties. Conclusions: These data indicate that while calcitriol effectively lowered PTH in rats with CKD, it did little to prevent the negative effects of secondary hyperparathyroidism on the skeleton.

scholarly journals RELATIONSHIP OF ADOLESCENTS BEHAVIOR TO CONSUMPTION OF SOFT DRINKS IN SMPN 5 PEKANBARU YEAR 2016

1930 ◽  
Vol 7 (02) ◽  
pp. 53-60
Author(s):  
Alhidayati ◽  
Nurhapipa ◽  
Rahma Putri
Keyword(s):  
Negative Impact ◽  
Calcium Deficiency ◽  
Soft Drinks ◽  
The Body ◽  
P Value ◽  
Negative Effects ◽  
Chi Square ◽  
Cross Sectional ◽  
The Impact

Behavior consumption of soft drinks are the actions or deeds regarding how often consume soft drinks per week is calculated. Carbonated drinks consumption habits will have a negative impact when it accumulates in the long term. Have been many studies that explain the negative effects of soft drinks, including carcinogenic benzene in soft drinks is very high, high phosphate content of vital minerals in the body that can trigger heart disease (magnesiumdeficiency), osteoporosis (calcium deficiency) and more. Based on the survey results of the sale of soft drinks in the cafeteria, 5 schools with the highest sales level, is SMP N 5 Pekanbaru selling 6-7 boxes per month. This type of research is quantitative with cross sectional design which was held on 16-18 May 2016 in SMP N 5 Pekanbaru. The population of this research is all student grades 7 and 8 SMP N 5 Pekanbaru which amounted to 541 people, with a sample size of 115 people. Data collected technique by stratified random sampling use questionnaire measuring instrument. Univariate data analysis and use your bivariate chi-square test. The results showed that there was a relationship between the knowledge obtained value (p value = 0.001 value POR = 2.14), Effect of friends (p value = 0.006 value POR = 3.45), Access (p value = 0.029 value POR = 2.70), And advertisement (p value = 0:01 value POR = 3.20) with the consumption of soft drinks. Suggested to the relevant instance, that is SMP N 5 Pekanbaru to provide education and information to as many students on the impact of consuming soft drinks for health when consumed in the long term and excessive, and form healthy canteen, or supervise the beverage products , to minimize the beverage products are bad for health.

scholarly journals The potential impact of the COVID-19 pandemic on tuberculosis: a modelling analysis

2020 ◽  
Author(s):  
Lucia Cilloni ◽  
Han Fu ◽  
Juan F Vesga ◽  
David Dowdy ◽  
Carel Pretorius ◽  
...  
Keyword(s):  
Negative Impact ◽  
Negative Effects ◽  
High Burden ◽  
Targeted Interventions ◽  
Modelling Analysis ◽  
Incidence And Mortality ◽  
Negative Impacts ◽  
Epidemiological Impact ◽  
The Impact

Background Routine services for tuberculosis (TB) are being disrupted by stringent lockdowns against the novel SARS-CoV-2 virus. We sought to estimate the potential long-term epidemiological impact of such disruptions on TB burden in high-burden countries, and how this negative impact could be mitigated. Methods We adapted mathematical models of TB transmission in three high-burden countries (India, Kenya and Ukraine) to incorporate lockdown-associated disruptions in the TB care cascade. The anticipated level of disruption reflected consensus from a rapid expert consultation. We modelled the impact of these disruptions on TB incidence and mortality over the next five years, and also considered potential interventions to curtail this impact. Results Even temporary disruptions can cause long-term increases in TB incidence and mortality. We estimated that a 3-month lockdown, followed by 10 months to restore normal TB services, would cause, over the next 5 years, an additional 1.92 million TB cases (Crl 1.74 - 2.15) and 488,000 TB deaths (CrI 449 - 541 thousand) in India, 48,000 (33,400 - 72,320) TB cases and 16,800 deaths (11.9 - 21.9 thousand) in Kenya, and 9,100 (6,980 - 11,200) cases and 1,960 deaths (1,620 - 2,350) in Ukraine. However, any such negative impacts could be averted through supplementary 'catch-up' TB case detection and treatment, once restrictions are eased. Interpretation Lockdown-related disruptions can cause long-lasting increases in TB burden, but these negative effects can be mitigated with targeted interventions implemented rapidly once lockdowns are lifted.

scholarly journals Type 2 diabetes mellitus and sepsis: state of the art, certainties and missing evidence

2021 ◽  
Author(s):  
Elisa Costantini ◽  
Massimiliano Carlin ◽  
Massimo Porta ◽  
Maria Felice Brizzi
Keyword(s):  
Glycemic Control ◽  
Current Knowledge ◽  
Kidney Injury ◽  
Protective Role ◽  
Control Treatment ◽  
Diabetic Patients ◽  
Incidence And Mortality ◽  
Pubmed Search ◽  
Severe Infections ◽  
The Impact

AbstractDiabetes and sepsis are important causes of morbidity and mortality worldwide, and diabetic patients represent the largest population experiencing post-sepsis complications and rising mortality. Dysregulated immune pathways commonly found in both sepsis and diabetes contribute to worsen the host response in diabetic patients with sepsis. The impact of diabetes on mortality from sepsis is still controversial. Whereas a substantial proportion of severe infections can be attributed to poor glycemic control, treatment with insulin, metformin and thiazolidinediones may be associated with lower incidence and mortality for sepsis. It has been suggested that chronic exposure to high glucose might enhance immune adaptation, leading to reduced mortality rate in septic diabetic patients. On the other hand, higher risk of acute kidney injury has been extensively documented and a suggested lower risk of acute respiratory distress syndrome has been recently questioned. Additional investigations are ongoing to confirm the protective role of some anti-diabetic treatments, the occurrence of acute organ dysfunction, and the risk/benefit of less stringent glycemic control in diabetic patients experiencing sepsis. Based on a MEDLINE/PubMed search from inception to December 31, 2020, the aim of this review is therefore to summarize the strengths and weaknesses of current knowledge on the interplay between diabetes and sepsis.

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