Role of Diffusion-Weighted MRI (DWI-MRI) in the Diagnosis of Brain Complications caused by Heroin Substance Abuse

Background: Magnetic resonance imaging (MRI) offers higher diagnostic accuracy for brain lesions caused by heroin abuse compared to compute tomography (CT) scan. These lesions have a low signal on T1-weighted (T1W) images and a high signal on T2-weighted (T2W) and fluid-attenuated inversion recovery (FLAIR) images. This study aimed to evaluate the role of diffusion-weighted MRI (DWI-MRI) in heroin addicts.Methods: This cross-sectional study was conducted on 20 patients with heroin addiction (vapor inhalation/injection) referring to Imam Reza Hospital of Mashhad, Iran. Patients in whom heroin abuse was only cause of consciousness, loss and neurological symptoms were enrolled in this study. Demographic data of the patients were recorded, including MRI, FLAIR, T1W and T2W images. In addition, DWI of axial and sagittal sections of the brain was performed in the following sequences.Results: In this study, mean age of patients was 40.15±7.673 years, and 95% of patients were male. The most common mode of heroin use was inhalation, and mean duration of addiction was 5.48±3.393 years. Mean daily intake of heroin was 13.4±15.30 grams, and mean duration of heroin abuse was 10.3 and 4.6 years in patients with and without MRI changes, respectively. A significant correlation was observed between MRI changes and duration of heroin use (r=0.721) (p=0.001). In addition, a significant correlation was observed between MRI changes and daily intake of heroin (p=0.006).Conclusion: According to the results of this study, brain lesions caused by heroin abuse have a low signal on T1W images and a high signal on T2W and FLAIR images. Therefore, it could be concluded that heroin intake has significant effects on the brain of users

Identify successful restrictions in suppressing the early outbreak of COVID-19 in Arizona, United States: Interrupted time series analysis

COVID-19 was responsible for many deaths and economic losses around the globe since its first case report. Governments implemented a variety of policies to combat the pandemic in order to protect their citizens and save lives. Early in 2020, the first cases were reported in Arizona State and continued to rise until the discovery of the vaccine in 2021. A variety of strategies and interventions to stop or decelerate the spread of the pandemic has been considered. It is recommended to define which strategy was successful for disease propagation prevention and could be used in further similar situations. This study aimed to evaluate the effect of people's contact interventions strategies which were implemented in Arizona State and their effect on reducing the daily new COVID-19 cases and deaths. Their effect on daily COVID-19 cases and deaths were evaluated using an interrupted time series analysis during the pandemic's first peaks to better understand the onward situation. Canceling the order of staying at home (95% CI, 1718.52 to 6218.79; p<0.001) and expiring large gatherings (95% CI, 1984.99 to 7060.26; p<0.001) on June 30 and August 17, 2020, respectively, had a significant effect on the pandemic, leading to the daily cases to grow rapidly. Moreover, canceling the stay at home orders led to an increase in the number of COVID-19 daily deaths by 67.68 cases (95% CI, 27.96 to 107.40; p<0.001) after about 21 days while prohibiting large gatherings significantly decreased 66.76 (95% CI: 20.56 to 112.96; p = 0.004) the number of daily deaths with about 21 days' lag. The results showed that strategies aimed at reducing people's contact with one another could successfully help fight the pandemic. Findings from this study provide important evidence to support state-level policies that require observance of social distancing by the general public for future pandemics. Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Examining of Thallium in Cigarette Smokers

Abstract Smoking is one of the sources of thallium which is considered as a toxic heavy metal. The aim of this study was to determine urinary thallium levels and related variables in smokers, compared to a control group. The study was conducted on 56 participants who had smoked continuously during the year before they were referred to Kashan Smoking Cessation Clinic. Fifty-three nonsmokers who were family members or friends of the smokers were selected as the control group. Urinary thallium was measured in both groups (n = 109) using atomic absorption spectrophotometry. The mean value (with SD) for urinary thallium in the smokers (10.16 ± 1.82 μg/L) was significantly higher than in the control group (2.39 ± 0.63 μg/L). There was a significant relationship between smoking duration and urinary thallium levels (P = 0.003). In a subgroup of smokers who was addicted to opium and opium residues (n = 9), the mean level of thallium (37.5 ± 13.09 μg/L) was significantly higher than in the other smokers (4.93 ± 4.45; P = 0.001). Multiple regression analysis showed opioid abuse, insomnia, and chronic obstructive pulmonary disease (COPD), together were strong predictors of urinary thallium levels in smokers. There was no significant difference in thallium level in hookah smokers (P = 0.299) or in those with COPD compared to other smokers (P = 0.375). Urinary thallium levels of smokers with clinical signs of depression, sleep disorders, memory loss, and sweating were higher than those of smokers without these signs. Since thallium, as other toxic metals is accumulated in the body, and cigarette smoking also involves carcinogenic exposures and health hazards for passively exposed people, the need for cigarette control policies is emphasized. Keywords: Thallium Smoking Urinary level Poisonin

Oral consumption of α-linolenic acid increases serum BDNF levels in healthy adult humans

Background aims: Dietary omega-6 and omega-3 fatty acids have remarkable impacts on the levels of DHA in the brain and retina. Low levels of DHA in plasma and blood hamper visual and neural development in children and cause dementia and cognitive decline in adults. The level of brain-derived neurotrophic factors (BDNF) changes with dietary omega-3 fatty acid intake. BDNF is known for its effects on promoting neurogenesis and neuronal survival. Methods: In this study, we examined the effect of the oral consumption of α-Linolenic acid (ALA) on blood levels of BDNF and Malondialdehyde (MDA) in healthy adult humans. 30 healthy volunteers, 15 men and 15 women, were selected randomly. Each individual served as his or her own control. Before consuming the Flaxseed oil capsules, 5cc blood from each individual was sampled in order to measure the plasma levels of BDNF and MDA as baseline controls. During the experiment, each individual was given 3 oral capsules of flaxseed oil, containing 500mg of alpha linolenic acid, daily for one week. Then, plasma levels of BDNF and MDA were tested. Results: The plasma levels of BDNF and MDA significantly (P < 0.05) increased in individuals who received the oral capsules of ALA. Plasma levels of BDNF increased more in the women in comparison with the men. Conclusion: ALA treatment could be a feasible approach to reduce size of infarcts in stroke patients. Thus, ALA could be used in adjunction with routine stroke therapies to minimize brain lesions caused by stroke. © 2015 Hadjighassem et al.; licensee BioMed Central

Effects of low-intensity continuous ultrasound on hematological parameters of rats

Background: Low intensity ultrasound (US) has some well-known bio-effects which are of great importance to be considered. Objective: We conducted the present study to investigate the effects of low intensity continuous ultrasound on blood cells count in rat. Methods: Rats were anesthetized and blood samples were collected before US exposure. Then, they were exposed to US with nominal intensity of 0.2 W/cm2 at frequency of 3 MHz for a period of 10 minutes and this protocol was repeated for 7 days. Twenty four hours after the last US exposure, secondary blood samples were collected and the changes in blood parameters were evaluated. Results: Analysis revealed that platelets, hematocrit (HCT) and hemoglobin (HGB) were significantly different between experimental and sham groups but no difference between sham and control groups was observed. The results show that HCT and HGB of exposed rats were significantly reduced. Conclusion: This study shows that low intensity US may lead to side effects for hematological parameters such as reduction in the levels of HGB and HCT. © 2016 Shiraz University of Medical Sciences. All rights reserved

Correction to: Comparison of Vitamin B12, Vitamin D, and Folic Acid Blood Levels in Plumbism Patients and Controls in Eastern Iran (Biological Trace Element Research, (2021), 199, 1, (9-17), 10.1007/s12011-020-02119-6)

The original version of this article unfortunately contained mistakes. & The name of �Namam Ali Azadi� is now corrected in the author group & Fourth to seventh sentence of the Abstract section should be �The results indicated that the mean vitamin B12, vitamin D, and folic acid levels for the case group were 517.3 ± 419.4 pg/ml, 25.1 ± 10.8 ng/ml, and 9.2 ± 6.1 ng/ml, respectively. Mean folic acid level in the case group was significantly lower than control group (Fisher exact test, P < 0.001), whereas the mean of the vitamin D levels at the case group was no significantly higher than the control group (Fisher exact test, P = 0.059). Moreover, mean vitamin B12 levels were significantly different between the case and control groups (Fisher exact test, P = 0.009). In the control group, three patients had folic acid below normal level (< 6 ng/mL), while twelve subjects at case group had folic acid below normal level (P < 0.05).Also, none of the control group had low vitamin B12 concentrations (< 180 pg/ml), while seven subjects of case group had vitamin B12 below normal level (P < 0.05).� & In page 6, Discussion part, 4th paragraph: We found that mean blood folate levels in the lead-poisoned patients, who had a mean BLL of 66 ± 37. 3 µg/dl, were significantly lower than in healthy subjects (9.2 ± 6.1 ng/ml vs. 12.70 pg/ml). © 2020, Springer Science+Business Media, LLC, part of Springer Nature

Cathepsin D protects colorectal cancer cells from acetate-induced apoptosis through autophagy-independent degradation of damaged mitochondria

Acetate is a short-chain fatty acid secreted by Propionibacteria from the human intestine, known to induce mitochondrial apoptotic death in colorectal cancer (CRC) cells. We previously established that acetate also induces lysosome membrane permeabilization in CRC cells, associated with release of the lysosomal protease cathepsin D (CatD), which has a well-established role in the mitochondrial apoptotic cascade. Unexpectedly, we showed that CatD has an antiapoptotic role in this process, as pepstatin A (a CatD inhibitor) increased acetate-induced apoptosis. These results mimicked our previous data in the yeast system showing that acetic acid activates a mitochondria-dependent apoptosis process associated with vacuolar membrane permeabilization and release of the vacuolar protease Pep4p, ortholog of mammalian CatD. Indeed, this protease was required for cell survival in a manner dependent on its catalytic activity and for efficient mitochondrial degradation independently of autophagy. In this study, we therefore assessed the role of CatD in acetate-induced mitochondrial alterations. We found that, similar to acetic acid in yeast, acetate-induced apoptosis is not associated with autophagy induction in CRC cells. Moreover, inhibition of CatD with small interfering RNA or pepstatin A enhanced apoptosis associated with higher mitochondrial dysfunction and increased mitochondrial mass. This effect seems to be specific, as inhibition of CatB and CatL with E-64d had no effect, nor were these proteases significantly released to the cytosol during acetate-induced apoptosis. Using yeast cells, we further show that the role of Pep4p in mitochondrial degradation depends on its protease activity and is complemented by CatD, indicating that this mechanism is conserved. In summary, the clues provided by the yeast model unveiled a novel CatD function in the degradation of damaged mitochondria when autophagy is impaired, which protects CRC cells from acetate-induced apoptosis. CatD inhibitors could therefore enhance acetate-mediated cancer cell death, presenting a novel strategy for prevention or therapy of CRC.FEDER through POFC – COMPETE and by Fundação para a Ciência e Tecnologia through projects PEst-OE/BIA/UI4050/2014 and FCT ANR/BEX-BCM/0175/201

The N-Terminal, Polybasic Region Is Critical for Prion Protein Neuroprotective Activity

Several lines of evidence suggest that the normal form of the prion protein, PrPC, exerts a neuroprotective activity against cellular stress or toxicity. One of the clearest examples of such activity is the ability of wild-type PrPC to suppress the spontaneous neurodegenerative phenotype of transgenic mice expressing a deleted form of PrP (Δ32–134, called F35). To define domains of PrP involved in its neuroprotective activity, we have analyzed the ability of several deletion mutants of PrP (Δ23–31, Δ23–111, and Δ23–134) to rescue the phenotype of Tg(F35) mice. Surprisingly, all of these mutants displayed greatly diminished rescue activity, although Δ23–31 PrP partially suppressed neuronal loss when expressed at very high levels. Our results pinpoint the N-terminal, polybasic domain as a critical determinant of PrPC neuroprotective activity, and suggest that identification of molecules interacting with this region will provide important clues regarding the normal function of the protein. Small molecule ligands targeting this region may also represent useful therapeutic agents for treatment of prion diseases

Therapeutic metformin/AMPK activation blocked lymphoma cell growth via inhibition of mTOR pathway and induction of autophagy

Adenosine monophosphate-activated protein kinase (AMPK) acts as a major sensor of cellular energy status in cancers and is critically involved in cell sensitivity to anticancer agents. Here, we showed that AMPK was inactivated in lymphoma and related to the upregulation of the mammalian target of rapamycin (mTOR) pathway. AMPK activator metformin potentially inhibited the growth of B- and T-lymphoma cells. Strong antitumor effect was also observed on primary lymphoma cells while sparing normal hematopoiesis ex vivo. Metformin-induced AMPK activation was associated with the inhibition of the mTOR signaling without involving AKT. Moreover, lymphoma cell response to the chemotherapeutic agent doxorubicin and mTOR inhibitor temsirolimus was significantly enhanced when co-treated with metformin. Pharmacologic and molecular knock-down of AMPK attenuated metformin-mediated lymphoma cell growth inhibition and drug sensitization. In vivo, metformin induced AMPK activation, mTOR inhibition and remarkably blocked tumor growth in murine lymphoma xenografts. Of note, metformin was equally effective when given orally. Combined treatment of oral metformin with doxorubicin or temsirolimus triggered lymphoma cell autophagy and functioned more efficiently than either agent alone. Taken together, these data provided first evidence for the growth-inhibitory and drug-sensitizing effect of metformin on lymphoma. Selectively targeting mTOR pathway through AMPK activation may thus represent a promising new strategy to improve treatment of lymphoma patients

Frequent expression loss of Inter-alpha-trypsin inhibitor heavy chain (ITIH) genes in multiple human solid tumors: A systematic expression analysis

<p>Abstract</p> <p>Background</p> <p>The inter-alpha-trypsin inhibitors (ITI) are a family of plasma protease inhibitors, assembled from a light chain – bikunin, encoded by <it>AMBP </it>– and five homologous heavy chains (encoded by <it>ITIH1</it>, <it>ITIH2</it>, <it>ITIH3</it>, <it>ITIH4</it>, and <it>ITIH5</it>), contributing to extracellular matrix stability by covalent linkage to hyaluronan. So far, ITIH molecules have been shown to play a particularly important role in inflammation and carcinogenesis.</p> <p>Methods</p> <p>We systematically investigated differential gene expression of the <it>ITIH </it>gene family, as well as <it>AMBP </it>and the interacting partner <it>TNFAIP6 </it>in 13 different human tumor entities (of breast, endometrium, ovary, cervix, stomach, small intestine, colon, rectum, lung, thyroid, prostate, kidney, and pancreas) using cDNA dot blot analysis (Cancer Profiling Array, CPA), semiquantitative RT-PCR and immunohistochemistry.</p> <p>Results</p> <p>We found that <it>ITIH </it>genes are clearly downregulated in multiple human solid tumors, including breast, colon and lung cancer. Thus, <it>ITIH </it>genes may represent a family of putative tumor suppressor genes that should be analyzed in greater detail in the future. For an initial detailed analysis we chose <it>ITIH2 </it>expression in human breast cancer. Loss of <it>ITIH2 </it>expression in 70% of cases (n = 50, CPA) could be confirmed by real-time PCR in an additional set of breast cancers (n = 36). Next we studied ITIH2 expression on the protein level by analyzing a comprehensive tissue micro array including 185 invasive breast cancer specimens. We found a strong correlation (p < 0.001) between ITIH2 expression and estrogen receptor (ER) expression indicating that ER may be involved in the regulation of this ECM molecule.</p> <p>Conclusion</p> <p>Altogether, this is the first systematic analysis on the differential expression of <it>ITIH </it>genes in human cancer, showing frequent downregulation that may be associated with initiation and/or progression of these malignancies.</p