1- Introduction

2- Materials and methods

3- Results

4- Discussion

References

Abstract

Introduction: Long non-coding RNAs (lncRNAs) are RNA molecules that structurally resemble mRNA but do not encode proteins. Studies have been associated this class of non-coding RNA with the development of several disease, among them the different types of leukemia. However, the results are contradictory. Thus, we performed a systematic review of the literature available in order to better understand the involvement of lncRNAs in the development of leukemia. Materials and Methods: Pubmed and Embase databases were used to identify all studies that evaluated the expression of one or more lncRNA between human samples (peripheral blood, bone marrow) with leukemia (cases) and without leukemia (controls). Results: A total of 3675 articles were found in the databases, and after exclusion of articles that did not meet the eligibility criteria, 86 articles were included in this systematic review. In the 86 included studies, 3927 lncRNAs were differentially expressed between cases and controls. Among these, 110 lncRNAs were reported as being altered in samples from at least 2 studies and only 16 of them in ≥ 3 studies, which were selected for further evaluation. Of these, 12 lncRNAs were consistently dysregulated between cases and controls (CCAT1, CCDC26, CRNDE, HOTAIR, KCNQ5IT1, LINC00265, MALAT1, PVT1, SNHG5,TUG1: increased in cases, MEG3 and NEAT1: decreased in cases) in human samples of patients with some type of leukemia. Conclusion: Our data demonstrate that 12 lncRNAs are dysregulated in leukemia.

Introduction

Leukemia is a type of cancer that affects the blood and bone marrow and is characterized by the uncontrolled production and accumulation of blood cells (1). According to American Cancer Society (2), cancer the second leading cause of deaths among children, adolescents and young adults younger than 20 years, and leukemia is the main type of cancer that affect children. In addition, 381,774 people are living with or in remission from leukemia in the US (2). Radiation exposure, viral infections, ethnicity, gender and genetic mutations are some of the risk factors of leukemia (1). However, more studies are necessary to better understand the development and the pathogenesis of the different types of leukemia. In this context, epigenetic factors, such as non-coding RNAs (ncRNA), have been associated with leukemia development. NcRNAs are a group of regulatory RNAs that are not translated into protein (3). NcRNAs longer than 200 nucleotides are classified as long non-coding RNAs (lncRNAs). LncRNAs are located in nucleus, where they can act as molecular scaffolds, help in alternative splicing or modify chromatin structures. In addition, there are some lncRNAs that have functions in cytoplasm, such as modulating translation, promoting or inhibiting mRNA degradation, and acting as miRNAs sponges (4).

1- Introduction

2- DDS for targeted BC treatment

3- Conclusion and outlook

References

Abstract

Bladder cancer is a severe disease that threatens human health. The high recurrence rate and severe side-effects of traditional bladder cancer therapy require more efficient and higher targeting treatment. Drug delivery systems especially being endowed with the targeting property may provide a feasible means to solve such problems. Herein, we have reviewed the recent progress of the drug delivery systems aiming at bladder cancer therapy especially focusing on their targeting strategies. Additionally, we give some outlook of the design on targeting strategy for more effective anti-cancer applications.

Introduction

Cancer is a category of disease originating from unregulated cell growth and such abnormal cells are able to spread or invade other parts of our body. It is a major public health problem and becomes the second leading cause of death worldwide. Among them, bladder cancer (BC) tops the list of the estimated new cases and deaths [1]. In Europe, BC is the 5th most common cancer type for both sexes affecting rather men than women [2]. In US, BC ranks the 4th most common caner and the 8th in mortality in men [1]. In principle, BC is a rather heterogeneous disease, resulting in a challenge in classification, staging and grading. Generally, 70% of bladder urothelial cell carcinomas represent a superficial disease called nonmuscle-invasive BC, while the other 30% develop a muscle-invasive disease bearing the risk of metastatic spread of the tumor [3]. The standard scheme for superficial BC treatment is surgical transurethal resection with an 80% early success rate. Unfortunately, among them, 70% of those patients develop tumor recurrence within 5 years after surgical transurethal resection [4]. Therefore, chemotherapy still plays an important role in the prevention of tumor recurrence and progression. Although systemic or intravesical chemotherapy using the first-line chemotherapeutic agents (cisplatin, taxanes, gemcitabine, etc.) enables long-term survival in some patients, the high recurrence rate and severe side-effects still hinder BC therapy. Thus, more efficient and higher targeting treatment is in urgent need to improve the quality of the BC patients’ lives.

1- Introduction

2- Methods

3- Results

4- Discussion

5- Conclusions

References

Abstract

Background
Most of the world’s population is not covered by cancer surveillance systems or vital registration, and worldwide/UN-regional cancer incidence is estimated using a variety of methods. Quantifying the cancer burden in children (<15 years) is more challenging than in adults; childhood cancer is rare and often presents with non-specific symptoms that mimic those of more prevalent infectious and nutritional conditions.
Methods
A Baseline Model (BM) was constructed comprising a set of quality assured sex- and age-specific cancer rates derived from the US Surveillance, Epidemiology and End Results (SEER) program, for diagnostic groups of the International Classification of Childhood Cancers (ICCC-3) 3rd edition, and information on a known risk factor for endemic Burkitt lymphoma and Kaposi’s sarcoma. These rates were applied to global country-level population data for 2015 to estimate the global and regional incidence of childhood cancer. Results were compared to GLOBOCAN 2018, extrapolations from the International Incidence of Childhood Cancer (IICC-3) and estimates from the Global Childhood Cancer (GCC) model (based on IICC-3 data combined with information on health care systems and other parameters). Results
The BM estimated 360,114 total childhood cancers occurring worldwide in 2015; 54% in Asia and 28% in Africa. BM estimated standardised rates ranged from ∼178 cases per million in Europe and North America, through to ∼218 cases per million in West and Middle Africa. Totals from GLOBOCAN and extrapolations from the IICC-3 study were lower (44.6% and 34.7% respectively), but the estimate from the GCC model was 10.2% higher. In all models, agreement was good in countries with very high human development index (HDI), but more variable in countries with medium and low HDIs; the discrepancies correlating with registration coverage across these settings.
Conclusion
Disagreements between the BM estimates and other sources occur in areas where health systems are insufficiently equipped to provide adequate access to diagnosis, treatment, and supportive care. Incorporating aetiological evidence into the BM enabled the estimation of the additional burden of Burkitt lymphoma and Kaposi sarcoma; similar adjustments could be applied to other cancers, as and when information becomes available.

Conclusions

Using the original baseline model (BM) we estimated that approximately 360,000 cancers occurred in children in 2015 worldwide. These data were derived by imputing identical background incidence of childhood cancer to all world regions and correcting them for an effect of P. falciparum infection according to the known spread of this exposure. Our approach suggests that up to 45% of incident childhood cancers may be undocumented within existing (childhood) cancer surveillance systems. A majority of the children whose cancer diagnoses are missed reside in countries with lower human development index; indicating a need for improved provision, accessibility and utilisation of appropriate diagnostics and care and documentation of diagnosed cases.

Embolic stroke of undetermined source (ESUS)

Individual risk factors

laboratory work-up

Hypercoagulable profile

Evaluation for malignancy

Genetic considerations for cryptogenic stroke

Substance use and abuse

Infectious considerations

Summary

Disclosure

References

INTRODUCTION

The diagnosis of cryptogenic stroke (CS) is made by exclusion. There are a variety of stroke definitions, advancements in diagnostic technologies, along with differing thoughts on appropriate etiologic investigations, and there are more than 200 known causes of ischemic stroke (IS) requiring elimination. Despite an extensive evaluation the cause of CS cannot be determined in 30% to 40% of cases. It is important to determine the cause of CS to understand the functional prognosis and eliminate the risk of stroke recurrence by providing appropriate secondary stroke prevention. In clinical practice, the diagnosis of CS is considered when the diagnostic assessment is not complete, when a single cause cannot be determined because there are several potential causes, or there is no identifiable cause despite an extensive evaluation. Understanding stroke subtype is essential for managing acute interventions and secondary prevention. One prominently used classification system, designed for the TRIAL of ORG-10172 for Acute Stroke Treatment (TOAST), defined an undetermined stroke as a “brain infarction that is not attributable to a cardio-embolic source, large artery atherosclerosis, or small-vessel disease, despite an extensive vascular, cardiac and serologic evaluation.” As such, the definition is thought of in negative terms, based on the absence of findings.

SUMMARY

The specific cause of stroke in a large number of patients continues to challenge clinicians despite efforts to arrive at a CS diagnosis. Approximately 30% to 40% of ischemic strokes do not have a definitive cause despite specialized, costly testing, that often results in diminishing yield. Understanding the pathogenic mechanism of stroke, lack of Class I evidence, the workup and treatment strategies often vary considerably. CS incorporates a heterogenous group of patients leading to therapeutic implications based on the potential mechanism. In the absence of AFib, antiplatelet therapy continues to be the mainstay of treatment, though scientific evidence to support this is limited. In addition, risk factor management and lifestyle modifications, lead to improved stroke prevention strategies in patients with CS.

Colon cancer is one of the most commonly detected pathology and is the third worldwide cause of death in the US and Europe and ranks second with regard to the incidence of malignant tumors in population. Raman spectroscopy and imaging can be used for colon cancer detection and bioanalytical characterization of noncancerous and pathologically changed tissues. These studies included Raman spectroscopy measurement of not fixed and not stained tissues samples. Presented study included patients from Poland, who were ≥18 years of age and underwent colon cancer surgery. Outcomes were measured using confocal Raman microscope, spectroscopy results were compared with traditional histopathology analysis outcomes. DNA, lipids, proteins and carotenoids can be treated as biomarkers of cancerogenesis. Ratios: 751/1156 (DNA/Carotenoids), 1228/1332 (β -sheet/α -helix proteins conformation), 1586/1004 (Phosphorylated proteins/Proteins), 2854/2935 (Lipids/Proteins) can be used to differentiate noncancerous and cancerous human sigmoid colon mucosa based on Raman spectroscopy and imaging. We have proved that Raman spectroscopy and imaging are a powerful technique to distinguish between noncancerous and cancerous human sigmoid colon mucosa and to characterize biochemical composition of multilayer sigmoid colon tissues samples.

Introduction

Nowadays Raman spectroscopy and imaging have been recognized as a powerful tool in bioanalytical, biochemical and medical applications. High sensitivity and specificity, above 90%, especially related to the fingerprint region of Raman spectr a , offer precise identification of biomarkers based on their unique vibrations. The great advantage of Raman spectroscopy and imaging is also related to the fact that samples analysis doesn’t require any staining, which is beneficial in terms of time -consuming protocols and analysis costs . As a consequence , Raman based methods including Raman spectroscopy and imaging have emerged in last years as one of the most important alternative s for traditional ex vivo human tissue examination by H&E staining and highly efficient tool for biomedical applications [ 1 – 11]. A considerable progress in the field of in vivo – clinical assessment, especially due to the spectroscopic fiber technologies is also observed [12, 13]. Colon cancer , one of the most commonly detected pathology is the third worldwide cause of death with mortality around 60% in the United States and Europe and ranks second with regard to the incidence of malignant tumors in population [14]. The main endoscopic examination used in clinical practice for colon cancer screening is colonoscopy. However, colonoscopy has some disadvantages and risk such as colonic perforation occurring in approximately 1 in 1000 cases, or hemorrhagic complications that may occur during or after colonoscopy. When combined with anesthesia, other difficulties may include cardiovascular complications such as a temporary drop in blood pressure, the risk of blood clots, pulmonary embolism or deep vein thrombosis.

1- Introduction

2- Experimental procedures

3- Results

4- Discussion

5- Conclusion

References

Abstract

Exposure of NMDA receptor antagonists during developmental stages leads to behavioral consequences like attention deficit hyperactivity disorder (ADHD). However, the underlying molecular mechanisms have remained poorly understood. Herein, we studied the phosphorylated Akt (pAkt) and caspase-3, the key regulators of neuronal cell survival/death, as the probable downstream targets of MK-801 often used to engender ADHD-like condition. Swiss albino mice at postnatal days (PND) 7, 14 or 21 were injected with a single dose of MK-801 and evaluated for hyperactivity (open field test) and memory deficit at adolescence (PND 30) and adult stages (PND 60). PND 7 or 14 treatment groups (but not PND 21) consistently showed hyperactivity at the adolescence stage. A significant increase in working and reference memory errors in radial arm maze was noted at the adolescence age. PND 7 group continued to display the symptoms even in adulthood. All the treatment groups showed a significant decrease in the percent alterations (Y-maze) and discrimination index (novel object recognition test) at adolescence age. A significant increase in caspase-3 expression was noted in the prefrontal cortex (PFC) and hippocampus, whereas increased pAkt was noticed only in the hippocampus, following a single injection of MK-801 at PND 7. Concurrently, PND 7 treatment group showed significantly decreased neuronal nuclei (NeuN) expression (a marker for mature neurons) in the dentate gyrus, cornu ammonis-3 and PFC, but not in cornu ammonis-1, at adolescence age. We suggest that the observed symptoms of ADHD at adolescence and adulthood stages may be linked to alteration in pAkt and caspase-3 followed MK-801 treatment at PND 7.

Introduction

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by hyperactivity, impaired attention and impulsiveness (Sroubek et al., 2013). Individuals with ADHD also show poor working memory and executive function (Holmes et al., 2014). ADHD is highly prevalent during childhood and frequently persists into adulthood (Kooij et al., 2010). It affects approximately 5–10% of children worldwide (Willcutt, 2012). Several studies correlate dysregulation in the neurotransmission of dopamine, norepinephrine, glutamate and serotonin systems with the appearance of ADHD symptoms (Russell, 2002; Sagvolden et al., 2005; Feldman and Reiff, 2014). Imaging studies showed the involvement of frontal-motor cortex circuitry in ADHD patients (Giedd et al., 2001; Clark et al., 2007). Previous reports indicate an involvement of multiple genetic factors as the etiological basis of ADHD, however, exposure to various environmental agents during neuronal development have been suggested as causal factors (Brondum, 2007; Faraone and Larsson, 2019). It is also reveal that ADHD is not a single pathophysiological entity, but involves multiple interacting factors (Faraone et al., 2015). Exposure to various pharmacological agents (ethanol, phencyclidine, ketamine, nitrous oxide, barbiturates, benzodiazepines, halothane, isoflurane and propofol) during synaptogenesis triggers apoptosis throughout the brain and leads to psychiatric disorders later in life (Ikonomidou et al., 1999; Olney et al., 2000). Largely synaptogenesis and other constructive anatomical developments occur during the first three weeks in the life of rodents.

1- INTRODUCTION

2- PATIENTS AND METHODS

3- RESULTS

4- DISCUSSION

References

Abstract

Acute undifferentiated leukemia (AUL) is rare and defined by the absence of bona fide myeloid and lymphoid markers. Little is known about its incidence, survival and optimal management in the recent time period. Based on a case observed in our clinic, we queried the Surveillance, Epidemiology, and End Results database between 2000 and 2016. A total of 1,888 cases of AUL were diagnosed (1.34 per million person-years). The incidence of AUL has significantly decreased over time. Compared to other acute leukemias, patients with AUL have the highest median age (74 years); in contrast to acute myeloid leukemia (AML, 65) and acute lymphoblastic leukemia (ALL, 12). Excluding patients with preexisting malignancies, 1,444 patients with AUL were analyzed for survival. Only 35% of AUL patients had received chemotherapy. Comparatively, 94% of ALL and 71% of AML cases received chemotherapy. Among AUL patients who received chemotherapy, the median survival was 12 months as opposed to 1 month in the group who did not receive chemotherapy (or unknown status). Among adults, AUL patients had the worst prognosis, with a median overall survival (OS) of 9 months, compared to 27 months in ALL and 13 months in AML. Among children, the median OS was superior for all three groups of leukemias, the OS of AUL patients being better than in AML and very similar to ALL. On multivariate analysis, older age and time period were associated with worse outcome. We describe here the largest series of cases with AUL published to date.

INTRODUCTION

The last three or four decades have seen significant progress in the diagnosis and treatment of acute leukemias. No longer a universally fatal disease, acute leukemia has become treatable and, in many instances, curable. Using immunologic and molecular markers, many different prognostic types of acute leukemia are recognized. Acute undifferentiated leukemia (AUL) is rare and has neither lymphoid nor myeloid lineage specific markers. In the 2016 update of the World Health Organization (WHO) classification of myeloid neoplasms, AUL is listed as a subcategory of mixed phenotype acute leukemia. In an earlier epidemiologic study, an incidence of 1.6 cases per 1 million person-years was described. Based on a case of AUL observed in our clinic, we queried the Surveillance, Epidemiology, and End Results (SEER) registry database and reviewed the pertinent literature.

1- Introduction

2- Method

3- Results

4- Discussion

5- Conclusion

References

Abstract

Purpose: To examine whether rest intervals of different durations (“High Rest, Low Frequency” v. “Low Rest, High Frequency”), and load at different force exertion levels with different repetition frequencies (“High Load, Low Repetition” v. “Low Load, High Repetition”) have an impact on muscle micro-trauma, as such micro-trauma over repetitive loading and long-term muscle overuse can lead to musculoskeletal disorders (MSDs).
Method: Twenty-four adult males (mean age: 24.1 years; 3.6 SD) were randomly assigned to one of 4 bicep muscle eccentric exercise treatment groups (n = 6; “High Load, Low Repetition; High Rest, Low Frequency”, “High Load, Low Repetition; Low Rest, High Frequency”, “Low Load, High Repetition; High Rest, Low Frequency”, or “Low Load, High Repetition; Low Rest, High Frequency”) with non-dominant arm to induce muscle micro-trauma reactions in serum. Subjects in all treatment groups had equivalent total work volume, total rest duration and total work duration for comparison of muscle micro-trauma between and within the treatment groups. Muscle micro-trauma biomarker serum Creatine Kinase (CK) level was measured pre-exercise (Day 0) and post-exercise on Days 1, 2, 4, and 8. ANOVA with repeated measures was used to examine significance of rest and load-repetition combination over pre and post experiment days, as well as possible interactions.
Result: CK levels fluctuated significantly across different “Day” (P = 0.0115). Interaction was disordinal and significant between “Day” and “Rest” (P = 0.0000), and “Load” and “Rest” (P = 0.0322). Under “High Load, Low Repetition” condition, CK levels on Day 4 were significantly higher than on Days 0 and 2; CK levels on Day 8 were significantly higher than Day 0. CK level peaked on Day 4. Under “Low Rest” Condition, CK level on Days 4 and 8 are significantly higher than Day 0.
Conclusion: Shorter but more frequent rest intervals led to more extreme muscle micro-traumatic responses than the longer but less frequent ones, especially under “High Load, Low Repetition” condition when non-dominant bicep brachii was subscribed with eccentric exercise regimen.
Relevance: to industry The exploration of how rest scheduling affects progression of microtrauma from a biomechanical and molecular level in this study furthers current understanding of the early stage development of WMSDs. With future studies’ further research and confirmation, the findings of this study may be able to serve as a first attempt to guide shift scheduling and job design at manufacturing facilities.

Introduction

The US Department of Labor defines work-related Musculoskeletal Disorders (WMSDs) as musculoskeletal system and connective tissue diseases and disorders, involving overexertion, repetitive motion and vibration that lead to living tissue sprains, strains, tears, as well as pain, swelling, and numbness. MSDs represent one of the leading causes of lost workdays in industry and are associated with major economic costs. Occupational Safety and Health Administration (OSHA) estimated that “work-related MSDs in the United States account for over 600,000 injuries and illnesses and 34 percent of all lost workdays reported to the Bureau of Labor Statistics (BLS, 2016). These disorders now account for one out of every three dollars spent on workers’ compensation. It is estimated that employers spend as much as 20 billion dollars a year (U.S.) on direct costs for MSD-related workers’ compensation, and up to five times that much for indirect costs, such as those associated with hiring and training replacement workers” (OSHA, 2014).

1- Introduction

2- Methods

3- Results

4- Discussion

5- Conclusion

References

Abstract

Transmissible vaccines may provide a promising solution for improving the control of infectious disease, particularly zoonotic pathogens with wildlife reservoirs. Although it is well known that heterogeneity in pathogen transmission impacts the spread of infectious disease, the effects of heterogeneity on vaccine transmission are largely unknown. Here we develop and analyze a mathematical model that quantifies the potential benefits of a transmissible vaccine in a population where transmission is heterogeneous between two subgroups. Our results demonstrate that the effect of heterogeneity on the benefit of vaccine transmission largely depends on the vaccine design and the pattern of vaccine administration across subgroups. Specifically, our results show that in most cases a transmissible vaccine designed to mirror the transmission of the pathogen is optimal. If the vaccination effort can be preferentially biased towards a given subgroup, a vaccine with a pattern of transmission opposite to that of the pathogen can become optimal in some cases. To better understand the consequences of heterogeneity on the effectiveness of a transmissible vaccine in the real world, we parameterized our model using data from Sin Nombre virus in deer mice (Peromyscus maniculatus). The results of this analysis reveal that when a vaccination campaign is limited in vaccine availability, a traditional vaccine must be administered primarily to males for the spread of Sin Nombre virus to be prevented. In contrast, a transmissible vaccine remains effective even when it cannot be preferentially administered to males.

Introduction

Zoonoses, particularly those circulating in wildlife populations, are a primary source of pathogens that infect humans [1]. The burden of such pathogens on human populations can be profound, as demonstrated in the 2014–2015 West African Ebola virus epidemic. The virus was transmitted from wild animal populations such as fruit bats and apes [2], and resulted in over 11,000 human deaths and cost over 3.6 billion dollars [3]. Such outbreaks highlight the need to develop costeffective strategies that mitigate zoonotic spillover into human populations. One strategy for reducing the spillover potential of zoonoses is to decrease the prevalence of infectious disease within wildlife reservoir populations. Both culling [4] and mass vaccination [4,5] have been used to control pathogens in wildlife reservoir populations. Though both strategies have been successful in some cases [4], the costs of implementation and the difficulties of delivering vaccine to wild animals limit their scope of applicability [6]. Transmissible vaccines are a novel tool that might overcome some of these challenges, allowing for pathogen reduction or even the prevention of pathogen spread in wildlife reservoirs.

1- Introduction

2- Methods

3- Results

4- Discussion

References

Abstract

Stress hormones have been shown to be important mediators in driving malignant growth and reducing treatment efficacy in breast cancer. Glucocorticoids can induce DNA damage through an inducible nitric oxide synthase (iNOS) mediated pathway to increase levels of nitric oxide (NO). Using an immune competent mouse breast cancer model and 66CL4 breast cancer cells we identified a novel role of NOS inhibition to reduce stress-induced breast cancer metastasis. On a mechanistic level we show that the glucocorticoid cortisol induces expression of keys genes associated with angiogenesis, as well as pro-tumourigenic immunomodulation. Transcriptomics analysis confirmed that in the lungs of tumour-bearing mice, stress significantly enriched pathways associated with tumourigenesis, some of which could be regulated with NOS inhibition. These results demonstrate the detrimental involvement of NOS in stress hormone signalling, and the potential future benefits of NOS inhibition in highly stressed patients.

Introduction

Psychological stress induces an increase in the circulating levels of stress hormones, including the glucocorticoid cortisol [1]. Epidemiological evidence has associated negative psychosocial factors, including chronic stress, with increased incidence and poorer survival in breast cancer patients [2]. Furthermore, multiple studies have linked psychological stress with biological processes involved in metastasis [3–5], findings of particular importance since the primary cause of breast cancer-related death is metastatic spread [6]. Glucocorticoid signalling, mediated through the glucocorticoid receptor (GR), has been shown to promote tumourigenesis and drug-resistance in triple negative breast cancer (TNBC) [7], and increases in expression of GR in breast tumours have been correlated with decreased survival [8]. GR antagonism has also previously been shown to induce apoptosis and, in combination with conventional chemotherapies, reduce tumour size in models of TNBC [9]. We have previously explored the mechanistic actions of psychological stress in breast cancer, and shown that stress hormone exposure can induce DNA damage in breast cancer through the generation of reactive oxygen and nitrogen species (ROS/RNS). We have also previously shown that glucocorticoids mediate a non-genomic effect on inducible nitric oxide synthase (iNOS), the enzyme that generates NO, and increase nitric oxide (NO) signalling in breast cancer cells [10]. Although iNOS is expressed in both ER+ and ER-breast cancers [11,12], expression of iNOS has been found to correlate with tumour progression and poor survival in basal-like breast cancers [13,14], indicating that NO activity may drive malignant growth and spread. As such, iNOS represents a potential target to abrogate the detrimental effects of psychological stress hormone signalling. Nitric oxide (NO) is an important signalling molecule modulating a range of functions within the cell, however the role of NO in tumour biology is complex and multifaceted [15]. Aspects of tumourigenic transformation can be driven by prolonged inflammation and exposure to high concentrations of NO, resulting in an increase in oxidative stress and subsequent DNA damage [16]. It is thought that NO may also be capable of driving transformation through the induction of angiogenesis and migration [17]. The highest concentrations of NO are produced by iNOS, and expression of iNOS has been shown to be positively correlated with tumour grade, stage and metastasis in breast cancer [11,18–20]. Several studies have shown that induction of iNOS expression in tumour cells promotes an increase in angiogenesis, and subsequently an increase in invasiveness and progression [16,21,22].

Methods

Results

Discussion

Conclusions and Implications

References

Abstract

Background: Pressure ulcers pose an important quality-of-care challenge in nursing homes, with serious consequences for residents’ health. We assessed the scalability of the On-Time Pressure Ulcer Prevention (On-Time) intervention strategy, developed by the Agency for Healthcare Research & Quality, in nursing homes nationwide.
Intervention: On-Time uses electronic health record reports to identify changes in resident pressure ulcer risk and facilitate multidisciplinary input into clinical decision making. Objective: To assess the scalability and impact of On-Time on pressure ulcer incidence in nursing homes.
Design: We used quasi-experimental methods, employing a difference-in-differences design, to compare the pre-post trends in pressure ulcer incidence in the treatment and comparison homes. Setting and participants: The study population included long-stay residents at high risk for developing pressure ulcers in 47 nursing homes and matched comparison homes in 17 states.
Measures: Stage 2 to 4 pressure ulcer incidence among long-stay residents who met the criteria for high risk, identified using an algorithm adapted from the Minimum Data Set 3.0 Percent of High-Risk Residents with Pressure Ulcers (Long Stay) measure.
Results: The overall decline in pressure ulcer rates for treatment relative to matched comparison homes was statistically insignificant (P > .05). A subgroup of heterogeneous homes experienced a statistically significant decline of 3.24 percentage points (61.0% relative decrease) in pressure ulcer rates relative to matched comparison homes, but no uniting characteristic common across homes readily explained their success.
Conclusions/Implications: Scalability of future health information technologyebased quality improvement interventions in nursing home settings requires nuanced implementation support, particularly around electronic health record report accessibility and accuracy.

Conclusions and Implications

Despite the lack of an overall effect, the study was able to increase understanding of the scalability and associated challenges of this EHRbased intervention in nursing homes. Specifically, this study shows that nursing home readiness to undertake EHR-dependent quality improvement is a function of staff commitment and preparation, and EHR vendor engagement. In the case of On-Time, the intervention really begins when the reports are accessible to staff to use within the change teams, something that is not easily achieved. Additional research is needed to understand how best to reduce the investment required to prepare (both for the facility and for the EHR vendor) so that the promise of EHR-based interventions to reduce the incidence of adverse effects can be realized.

Much effort is currently being placed into developing new blood tests for cancer diagnosis in the hope of moving cancer diagnosis earlier and by less invasive means than current techniques, e.g., biopsy. Current methods are expected to diagnose and begin treatment of cancer within 62 days of patient presentation, though due to high volume and pressures within the NHS in the UK any technique that can reduce time to diagnosis would allow reduction in the time to treat for patients. The use of vibrational spectroscopy, notably infrared (IR) spectroscopy, has been under investigation for many years with varying success. This technique holds promise as is would combine a generally well accepted test (a blood test) with analysis that is reagent free and cheap to run. It has been demonstrated that, when asked simple clinical questions (i.e., cancer vs. no cancer), results from spectroscopic studies are promising. However, in order to become a clinically useful tool, it is important that the test differentiates a variety of cancer types from healthy patients. This study has analysed plasma samples with attenuated total reflection Fourier-transform IR spectroscopy (ATR-FTIR), to establish if the technique is able to distinguish normal from primary or metastatic brain tumours. We have shown that when asked specific questions, i.e., highgrade glioma vs. low-grade glioma, the results show a significantly high accuracy (100%). Crucially, when combined with meningiomas and metastatic lesions, the accuracy remains high (88–100%) with only minimal overlap between the two metastatic adenocarcinoma groups. Therefore in a clinical setting, this novel technique demonstrates potential benefit when used in conjuction with existing diagnostic methods.

Introduction

Blood testing for cancer diagnostics is a popular ideal. It uses an acceptable patient test, i.e., a blood test, which is minimally-invasive and machine analysed, can be run on a mass scale, and can target specific markers circulating in the blood. Whilst some cancers can be identified by the use of biomarkers, there are currently no such markers for primary or metastatic brain tumours, nor are any biomarkers yet involved in a mass-screening programme [1]. Brain tumours, both primary and metastatic, often present with a range of non-specific symptoms. The diagnostic process involves a combination of history taking, examination and radiology to determine the presence of a tumour and its possible origin [2]. There are specific radiological appearances that can help differentiate between primary and metastatic brain tumours; however, these rules do not always hold true [3]. A brain tumour may also be the first presentation of a metastatic cancer from elsewhere within the body; this accounts for up to a quarter of brain tumours [4]. Currently, a combination of radiological imaging and histology is used to detect the primary origin of a brain tumour. When metastatic, pathologists can apply immunohistochemical stains to formalin-fixed paraffin-embedded (FFPE) tissue, within which a combination of positive and negative stains can help determine a primary site of origin. Over recent years the potential of vibrational spectroscopy has been touted as an ‘inexpensive, high throughput and reagent-free’ cancer diagnostic tool. In vivo studies have shown great promise using both tissue and blood component analysis with detection of cancer vs. non-cancer in many pilot studies showing promising results [5,6]. When considering biofluids, predominantly serum has been analysed for brain cancer, using attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy, with varying sample methods used [7]. This is due to the erythrocyte component in whole blood providing a strong interfering spectroscopic signal, likely masking the underlying changes seen in cancer vs. non-cancer patients [8]. The main limitations of these studies focus around different methods of sample preparation and analysis.

مقدمه

در حال حاضر تلاش های زیادی بابت توسعه ی آزمایش های جدید خونی برای تشخیص سرطان در حال انجام است بدین امید که بتوانیم پیش از وقوع، سرطان را تشخیص دهیم و از روش هایی کمتر تهاجمی به غیر از شیوه های فعلی مانند بیوپسی استفاده کنیم. انتظار می رود با روش های فعلی، سرطان را تشخیص و طی 62 روز از زمان معرفی بیمار، درمان سرطان را شروع کنیم، هر چند به علت حجم زیاد و فشارها در درون نهاد خدمات سلامت همگانی انگلستان (NHS)، هر شیوه ای که بتواند زمان تشخیص سرطان را کاهش دهد، باعث کاهش زمان درمان بیماران می شود. استفاده از طیف سنجی ارتعاشی، به ویژه طیف سنجی مادون قرمز (IR)، برای سالیان سال و با موفقیت های گوناگون بررسی شده است. در شرایط فعلی این شیوه موفقیت آمیز بوده است و به طور کلی آزمایشی کاملاً قابل قبول (آزمایش خون) را با تجزیه و تحلیلی عاری از واکنشگر و کم هزینه در اجرا ادغام کرده است. ثابت شده است که وقتی پرسش های بالینی ساده پرسیده می شود (یعنی سرطان در برابر عدم وجود سرطان)، نتایج مطالعات طیف نمایی امیدوار کننده هستند. با این حال، به منظور تبدیل شدن به یک ابزار بالینی مفید، مهم است که آزمایش از میان بیماران غیرسرطانی، گونه های مختلف سرطان را تشخیص دهد. این پژوهش، نمونه های پلاسما را با طیف سنجی بازتاب کلی تضعیف شده و طیف سنجی ﻣﺎﺩﻭﻥ ﻗﺮﻣﺰ ﺑﺎ ﺗﺒﺪﻳﻞ ﻓﻮﺭﻳﺮ (ATR-FTIR) آزمایش می کند تا این موضوع مشخص شود که آیا این شیوه قادر به تشخیص تومورهای مغزی طبیعی، اولیه و یا فراگستر است. نشان داده ایم که وقتی سوالات خاصی پرسیده می شود، یعنی گلیومای بسیار پیشرفته در مقابل گلیومای خفیف ، به طور چشمگیری، نتایج، دقت بالا (100٪) را نشان می دهند. دقت نتایج در مواردی که با مننژیوم ها و ضایعات فراگستر ادغام می شود، به شکل بسیار مهمی بالا می ماند (88 الی 100 درصد) و دو گروه آدنوکارسینوم فراگستر تنها همپوشانی کمی دارند. بنابراین، در یک محیط بالینی، این شیوه ی نوین، مزایای بالقوه ای را در هنگام استفاده با روش های موجود تشخیصی نشان می دهد.

1- Introduction

2- Methods

3- Results

4- Discussion

5- Conclusions

References

Abstract

Although epidemiological studies have identified an association between hearing loss and cognitive impairment, there is a lack of biological evidence detailing the mechanisms underlying this association. The present study investigated the effects of hearing loss on cognitive impairment using an at-risk model. In this animal model, amyloid-β (Aβ) was administered to the brain to such an extent that it did not cause cognitive impairments but made the brain vulnerable to risk factors. This study included four experimental groups based on hearing level and Aβ administration. Behavioral tests were conducted to evaluate cognitive function, and synaptic protein levels were measured in the hippocampus and prefrontal cortex. The group with hearing loss and Aβ administration showed significantly greater deficits on cognitive tests associated with the hippocampus than the other three groups (only Aβ administration, only hearing loss, and without hearing loss or Aβ administration). The hearing loss and Aβ administration group also had significantly lower levels of synaptic proteins in the hippocampus than the other groups. The present results suggest that hearing loss may act as a risk factor for cognitive impairment in Alzheimer’s disease. Additionally, the present findings indicate hearing loss may cause hippocampal synapses to be more vulnerable to Aβ-induced damage.

Introduction

In 2016, approximately 43.8 million people suffered from dementia worldwide. Furthermore, the worldwide death rate associated with dementia was 2.4 million people, which made it the fifth leading cause of death [1]. The leading cause of dementia is Alzheimer’s disease (AD) [2] and, therefore, there is an urgent need for the development of treatments for AD. Although much research has been conducted in this area, the currently available treatments for AD have yet to achieve significant clinical efficacy in that they can partially stabilize the symptoms of this disease but not correct it [3]. It is also important to identify risk factors for AD, as this information will allow us to develop methods preventing AD development or slowing disease progression. Age, family history, and heredity are the most important risk factors of AD [4] and can be used to predict its occurrence. However, these factors cannot be modified and, thus, cannot contribute to the prevention of AD. Recent epidemiological evidence suggests that there is an association between hearing loss and cognitive impairment [5–8] and other studies have shown that hearing loss may be a potentially modifiable risk factor of AD [9]. Approximately one-third of elderly people 65 years of age and older have hearing loss, which can be ameliorated by hearing aids and cochlear implants. Therefore, if hearing loss is a risk factor of cognitive impairment and its mechanisms can be identified, then the treatment of hearing loss can contribute to the prevention of AD. However, the causal relationship between hearing loss and AD remains controversial. For example, it has been suggested that the association between hearing loss and AD exists due to difficulties in cognitive function tests that patients with hearing loss experience due to poor verbal communication. Furthermore, the biological mechanisms that underlie this association have yet to be elucidated.