Introduction. The neurobiological mechanisms underlying the chemotherapy-induced neuropathic pain are only partially understood. Among them, microglia activation was identified as the key component of neuropathic pain. The aim of this study was to identify differentially expressed genes (DEGs) and pathways associated with vincristine-induced neuropathic pain by using bioinformatics analysis and observe the effects of oxycodone on these DEG expressions in a vincristine-induced microglia activation model. Methods. Based on microarray profile GSE53897, we identified DEGs between vincristine-induced neuropathic pain rats and the control group. Using the ToppGene database, the prioritization DEGs were screened and performed by gene ontology (GO) and signaling pathway enrichment. A protein-protein interaction (PPI) network was used to explore the relationship among DEGs. Then, we built the vincristine-induced microglia activation model and detected several DEG expressions by real-time polymerase chain reaction (PCR) and western blotting. Meanwhile, the effects of different concentrations of oxycodone on inflammatory response in primary microglia induced by vincristine were observed. Results. A total of 38 genes were differentially expressed between normal and vincristine-treated rats. GO and pathway enrichment analysis showed that prioritization DEGs are involved in cAMP metabolic process, inflammatory response, regulation of cell proliferation, and chemokine pathway. The in vitro studies showed that vincristine had dose-dependent cytotoxic effects in microglia. Compared to the control group, vincristine (0.001 μg/ml) could lead to inflammation in primary microglia induced by vincristine and upregulated the CXCL10, CXCL9, SFRP2, and PF4 mRNA and made an obvious reduction in IRF7 mRNA. At protein levels, oxycodone (50, 100 ng/ml) decreased the expression of CXCL10 and CXCL9 in activated microglia. Conclusion. Our study obtained several DEG expressions and signaling pathways in the vincristine-induced neuropathic pain rat model by bioinformatics analysis. Oxycodone could alleviate the vincristine-induced inflammatory signaling in primary microglia and downregulate some DEGs. Further molecular mechanisms need to be explored in the future.
http://bit.ly/2BtgZEu
Σάββατο 9 Φεβρουαρίου 2019
Investigation of Key Genes and Pathways in Inhibition of Oxycodone on Vincristine-Induced Microglia Activation by Using Bioinformatics Analysis
Pleural effusions induced by human herpesviruses in the immunocompetent host
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http://bit.ly/2I6LTZ4
Comparison of the diagnostic accuracy of markers of the acute phase of inflammation in cats. A preliminary evaluation
Abstract
Markers of acute inflammation are gaining broader acceptance in feline veterinary practice but the criteria of their diagnostic accuracy have mostly not been determined. The goal of this study was to compare the diagnostic accuracy of a variety of markers of inflammation that can be rapidly measured in everyday veterinary practice settings. White blood cell, as well as neutrophil and band cell count, degree of toxic neutrophilia, total proteins, albumin, albumin-to-globulin ratio, fibrinogen, and serum amyloid A protein were measured in 35 cats with acute inflammatory diseases and 16 control cats. The sensitivity, specificity, and receiver operating curves of these markers were then compared. The markers with the highest sensitivities and specificities, as well as areas-under-the-curve of the receiver operating curves > 0.9, were fibrinogen, serum amyloid A, degree of toxic neutrophilia, and albumin-to-globulin ratio. The correlations between the different markers were, with the exception of fibrinogen and SAA, low. SAA, fibrinogen, albumin-to-globulin ratio are a panel of sensitive inflammatory biochemistry biomarkers easily available for non specialist veterinarians improving the rapidity of feline patient assessment.
http://bit.ly/2US8iL1
Phylogenetic typing and virulence gene profile of pathogenic and commensal avian Escherichia coli in Iran: a notable finding
Abstract
The aim of this study was to compare phylogenic groups and virulence genes profiles of Escherichia coli isolated from poultry suffering from Colibacillosis with E.coli in the intestinal flora of healthy poultry. For this purpose, var, tsh, iucd, papc, irp2, and iss virulence genes of E. coli were investigated by multiplex PCR in 70 isolates (35 obtained from healthy samples and the other 35 isolated were attained form those with Colibacillosis) in Ardabil province, northwest of Iran. The phylogenic groups were also determined through use of PCR multiplex. Among them, 32 isolates (91%) of samples taken from poultry with Colibacillosis and 27 isolates (77%) from healthy samples contained papc gene. The results for iucd, var, and irp2 genes were 17 healthy and 20 diseased isolates, 23 healthy and 28 diseased isolates, and 32 healthy and 29 diseased isolates, respectively. In the case of tsh gene, only one isolate from healthy samples included the mentioned gene; while iss gene was observed in none of the isolates. In terms of phylogeny groups, except one, all the isolates belonged to the phylogenic group D. Results of present research revealed that the frequency of virulence genes and the diversity of phylogeny groups in isolates from healthy and diseased samples are not significantly different in the studied area.
http://bit.ly/2tdqF1c
Multicentric intrahepatic cholangiocellular carcinoma in a budgerigar ( Melopsittacus undulatus ): a case report
Abstract
Cholangiocarcinoma or intrahepatic bile duct carcinoma is a malignant neoplasm of biliary epithelium which occurs mainly in wild animals rather than domestic ones. An adult 4-year-old male budgerigar was referred with symptoms of lethargy, decreased activity, and vomiting with undigested food in feces. Supportive care was tried for 3 months, but the bird did not show any signs of recovery and was finally euthanized. Necropsy revealed hepatomegaly in one lobe of the liver while the other lobe was dwindled. The remaining large lobe had a multinodular appearance with white to gray, non-umbilicated foci ranging from 2 mm to 3 cm in diameter which was scattered throughout the parenchyma. The histopathological examination revealed multiple foci or masses of less differentiated cholangiocellular carcinoma. The large tumor masses had tubular, acinar, and solid arrangements with a center of necrosis. The masses were composed of neoplastic cells of biliary epithelium similar to the normal cuboidal ductal lining cells with moderate eosinophilic cytoplasm and round to oval vesicular nuclei. Multinuclear tumor giant cells were not seen; however, karyomegaly was rarely observed and infrequently in some foci. Based on histopathological characteristics, multicentric intrahepatic cholangiocellular carcinoma was confirmed. It seems that the probable cause of the tumor in this bird was chronic exposure to toxins such as aflatoxins.
http://bit.ly/2USqTHc
Evaluation of the serum fructosamine concentrations in transition period and its relationship with serum proteins and energy characteristics in dairy cows
Abstract
The relationship between fructosamine (FRUC) and glucose (GLU) amounts in dog was previously reported. On the other hand, no correlations were reported in transition dairy cow and late-pregnant sheep. Similar controversy also existed concerning the relationship between FRUC, albumin (ALB), and total protein (TP) concentrations. Thirty-three healthy Holstein cows were enrolled in to the study. Blood samples were obtained by jugular venipuncture at 3 and 1 weeks before and 1 and 3 weeks after calving. The concentrations of FRUC, GLU, ALB, TP, β hydroxybutyrate (BHBA), and non-esterified fatty acids (NEFA) were measured with automated biochemical analyzer, using commercial kits. SPSS software, version 20 (SPSS Inc., Chicago, USA) was used for data analysis. The mean ± SE of fructosamine for all cows during the study was 355.6 ± 4.5 μmol/l. There was significant difference in the serum concentration of FRUC post-partum, and throughout of trial, but not at pre-partum period. The maximum concentration of FRUC was at W−1 and decreased thereafter. There were significant positive correlations between FRUC and GLU concentrations at pre-partum, post-partum, and overall time of the study. There were significant negative correlations between FRUC and NEFA concentrations at pre-partum, post-partum, and overall time of the study. There were no correlations between FRUC, TP, ALB, and BHBA amounts at pre-partum, post-partum, and overall time of the study. Linear regression analysis between each sampling amount of GLU and three consecutive FRUC concentrations did not reveal significant correlation between GLU and FRUC. According to present results, fructosamine measurement could be considered as a useful indicator of energy economy in transition period.
http://bit.ly/2tcT9s5
Oxidative stress and toxicity effect of Echium amoenum on mice brain
Abstract
Echium amoenum (Boraginaceae) is one of the important medicinal herbs in traditional medicine. It was known for its various effects such as demulcent, anti-inflammatory, and analgesic, especially for common cold, anxiolytic, and sedative. This plant contains small quantities of pyrrolizidine alkaloids that are toxic, and chronic consumption may have adverse effects on the body's organs. The aim of this study is to investigate the role of Echium amoenum plant in neurotoxicity on the brain of mice. In this study, 40 mice were chosen and divided into four groups. Group (1) as control group (without injection), group (2) received 12.5 mg/kg, group (3) received 25 mg/kg, and group (4) received 50 mg/kg body weight plant. Boraginaceae was injected into mice for a month by intraperitoneal injection (i.p). Then, the mice were decapitated and brains were collected to evaluate oxidative stress. The level of lipid oxidation was significant in all groups except among high dose in comparison with control groups, and low with the intermediate dose. Changes in ion-reducing antioxidant capacity assay (CUPRAC) were not significant. The level of total glutathione (GH) increased in high dose. The histopathological study showed high dose leads to the lesion in the brain tissue. Echium amoenum may trigger toxicity in high doses; the authors recommended to avoid over-consumption.
http://bit.ly/2UMPmNS
Combined effects of dietary bovine lactoferrin, Lactobacillus plantarum , and xylooligosaccharide on hemato-immunological and digestive enzymes of silvery-black porgy ( Sparidentex hasta ) fingerlings
Abstract
A 6-week study was conducted to evaluate the effects of the following eight experimental diets, which varied in bovine lactoferrin (LF), xylooligosacharide (XOS), and Lactobacillus plantarum (LP) as probiotic silvery-black porgy (Sparidentex hasta) juveniles including control (diet 1), 400 mg kg−1 LF + 5 g kg−1 XOS (diet 2), 400 mg kg−1 LF + 10 g kg−1 XOS (diet 3), 400 mg kg−1 LF + 1 × 106 CFU g−1 LP (diet 4), 800 mg kg−1 LF + 5 g kg−1 XOS (diet 5), 800 mg kg−1 LF + 10 g kg−1 XOS (diet 6), and 400 mg kg−1 LF + 1 × 106 CFU g−1 LP (diet 7). Growth performance and humoral immune responses were not affected by different experimental groups (P > 0.05). Hematological parameters including red blood cell count, hemoglobin content, and hematocrit increased by supplementing diets with different combinations of immunostimulants (P < 0.05). Fish fed diet supplemented with 800 mg kg−1 LF + 5 g kg−1 XOS had highest total protease (1.0 ± 0.1 U mg protein−1) and α-amylase (34.9 ± 2.3 mg protein−1) activities (P < 0.05). Our results suggest that diets supplemented with selected levels of LF, XOS, and L. plantarum could not improve growth performance and humoral immunity, however improved hematological and digestive enzyme activities in S. hasta fingerlings.
http://bit.ly/2tdqsLs
Effect of Crotalaria lachnosema Stapf . (Fabaceae) extract on biomarkers of hepatic and renal function and oxidative stress in male Wistar rats
Abstract
The aim of this study was to determine the subchronic effect of Crotalaria lachnosema Stapf. (Fabaceae) extract (MLECL) on biochemical and oxidative stress biomarkers in male Wistar rats. The rats were assigned into four groups designated as groups 1(control), 2, 3, and 4, of ten rats each, and were exposed to dose levels of 0, 40, 200, and 1000 mg of MLECL extract per kilogram in feed, respectively, for a period of 6 weeks. At the end of the study period, the surviving rats were sacrificed and blood was collected from each rat via jugular venesection and used for biochemical analysis. Postmortem examination was carried out on euthanized rats after which tissue sections of various organs were harvested for histopathological examination. Exposure to the extract was found to significantly (p < 0.0001) increased the values of urea and creatinine in groups 2, 3, and 4 (urea, 4.32 ± 0.15, 3.92 ± 0.32, 4.14 ± 0.09 mmol/l and creatinine, 68.60 ± 1.99, 89.40 ± 5.61, 71.60 ± 3.67 μmol/l, respectively) when compared with group 1 (urea, 2.62 ± 0.10 mmol/l, creatinine, 42.80 ± 1.59 μmol/l, respectively). Similarly, the extract was found to significantly affect the serum levels of liver enzymes only in group 4 (ALT, 52.80 ± 2.11 IU/L; AST, 49.40 ± 2.25 IU/L; ALP, 92.20 ± 8.24 IU/L), (p < 0.05) than the corresponding values in the control group (ALT, 45.00 ± 1.52 IU/L; AST, 38.00 ± 1.52 IU/L; ALP, 61.60 ± 6.43 IU/L). Exposure to the extract had variable effects on the levels of the oxidative stress biomarkers, Superoxide dismutase (SOD) and catalase (CAT). The SOD levels were significantly (p < 0.05) lower in groups 2 and 3 with mean values of 1.96 ± 0.12 and 1.80 ± 0.07 IU/L, respectively, when compared to the control value of 2.36 ± 0.08 IU/L. The serum CAT value (40.20 ± 1.24 IU/L) was significantly (p < 0.05) lower only in group 3, when compared to the control value (45.80 ± 1.16 IU/L). Microscopic lesions observed in the MLECL-exposed groups were hepatic megalocytosis and severe congestion in the kidneys and lungs. Results from this study showed variable toxic effects induced by MLECL administration to male Wistar rats, especially low dose exposure to rats in groups 2 and 3. This could be attributed to pyrrolizidine alkaloid in MLECL.
http://bit.ly/2tdqqDk
The effects of different doses of onion ( Allium cepa. L) extract on leptin, ghrelin, total antioxidant capacity, and performance of suckling lambs
Abstract
Application of antibiotics in livestock production has been a big concern in the recent years since they can have a vital role in the emergence of antibiotic resistant bacteria. Therefore, scientists and nutritionists have been searching for alternative agents to alter ruminal metabolism and improve feed efficiency and animal productivity. In this respect, the aim of the present study was to evaluate the effects of onion extract on leptin, ghrelin, total antioxidant capacity (TAC), and the performance of suckling lambs. Eighteen Torki Qashqai suckling lambs with 30 days of age were randomly divided into three groups, including (1) control group; basement diet without onion extract + sheep milk, (2) T150 group; basement diet containing 150 mg/kg onion extract + sheep milk, (3) T250 group; basement diet containing 250 mg/kg onion extract + sheep milk. The trial lasted for 60 days and the blood samples were taken on days 30 and 60 of the experiment. The results showed that the addition of onion extract led to an increase in the feed intake and daily weight in lambs. Moreover, onion extract was able to increase the level of ghrelin and reduce leptin hormone in the treatment groups (T150 and T250). In conclusion, it could be said that onion extract has a promising effect as a feed additive in ruminant nutrition and has the ability to improve feed intake in these animals. Moreover, onion extract has a positive effect on concentrations of leptin, ghrelin, TAC, and the performance in lambs.
http://bit.ly/2tf0hnZ
Light and scanning electron microscopic study of the tongue in the guinea fowl ( Numida meleagris )
Abstract
Considering that, in birds, the tongue has an important role in taking food, so its shape and morphology are affected by the nutrition method and the environment of the animal. For this study, six adult female guinea fowl were prepared and, after slaughtering them humanely, their tongues were completely removed from the oral cavity and were completely washed with distilled water. After examining the morphology and measuring the tongue area, the tissue preparation stages were used for light and electron microscopes on each case. Morphological results showed that the tongue of the guinea fowl was triangular-shaped and the average length was 21.91 mm. The tongue consisted of three parts: apex, body, and root. The average length and width of apex were 8 and 6 mm, the average length and width of body were 6 mm and 8 mm, and the average root length and width were 7 and 9 mm, respectively. The examination of the tongue by a light microscope determined that the epithelium in the three parts of the tongue was keratinized stratified squamous, and the amount of keratinized on the ventral surface was more than on the dorsal surface. The connective tissue was of the dense irregular type and the salivary glands were observed in the root and body regions. The electron microscope results showed that the dorsal surface of the tongue contains filiform papillae which were more dense in the lateral edge than middle part of the tongue. A transverse row of giant conical papillae separated the body from the root of the tongue. In the ventral surface, from the root zone to the end region of the body, a concentric transverse fine eminence can be observed to be parallel to each other, and there was a ridge on the ventral surface along the length of the tongue, which has a reduction in its height from the root toward the apex. The glands' openings were mostly located in the root region of the tongue, and the density was higher on the dorsal surface than on the ventral surface.
http://bit.ly/2UPf8B1
Medical management of conjunctivitis and shell rot in a red-eared slider ( Trachemys scripta elegans )
Abstract
Conjunctivitis and shell rot in a red-eared slider and its successful clinical management are described. The red-eared slider was presented to Veterinary Polyclinic Mannarkkad with swollen eyes and white patches on the carapace. The turtle was treated with enrofloxacin bath for 7 days. Superficial lesions on the carapace were treated by application of chlorhexidine gel. Three percent boric acid was used for washing the eye. Vitamin A was administered orally. Several managemental changes ware also made to hasten the recovery. After 1 week of treatment, improvement in the condition of eye was observed. Within 1 month, the white patches on the carapace completely disappeared and the turtle made an uneventful recovery. The case points towards the importance of managemental changes that plays a significant role in the health of an exotic pet like red-eared slider.
http://bit.ly/2tdsOtV
Vitamin D supplementation enhanced oral glucose tolerance in normoglycemic rats and insulin sensitivity in rats fed high fat emulsion
Abstract
Several reports have suggested possible role of vitamin D deficiency in the pathogenesis of both type 1 and 2 diabetes. However, there is no agreement on the level of vitamin D requirement for optimum glycemic control. This work evaluated the effect of vitamin D supplementation on oral glucose tolerance (OGT) and insulin sensitivity, with the aim of determining the possible supplementation rate of vitamin D required for optimum glycemic control. Oral glucose tolerance was evaluated in normoglycemic rats, with vitamin D supplementation (VDS) at the rate of 0.07, 0.14, and 0.35 μg/kg orally for 28 days. Oral glucose tolerance (OGT) was evaluated by administration of 2000 mg/kg glucose/rat orally and blood glucose determined at 30, 60, and 120 min post glucose administration. Insulin sensitivity was evaluated in normoglycemic rats fed high fat emulsion (HFE) at the rate of 5 ml/kg/rat for 10 days and VDS was at the rate of 0.04, 0.05, 0.07, and 0.35 μg/kg for 38 days. Insulin (0.05 u/kg) was injected intraperitoneally to each rat, and blood glucose level determined at 5, 30, 60, and 120 min post insulin administration. Blood glucose of VDS rats was significantly (p < 0.05) lower than the vitamin D restricted group at 120 min. Significantly, (p < 0.05) higher OGT was recorded in the VDS groups. Insulin sensitivity (K) values showed inverse dose dependency with higher K values at lower vitamin D doses. Vitamin D supplementation enhanced glucose tolerance and insulin sensitivity at lower doses.
http://bit.ly/2UNYthl
Antioxidant effects of Allium cepa and cinnamon on biochemical parameters and ultrastructure of ovarian tissue in extremely low frequency electromagnetic field exposed rats
Abstract
We investigated whether 50 Hz wave (3 mT) extremely low frequency electromagnetic field (ELF-EMF) had effect on ovarian tissue biochemical parameters and whether Allium cepa and cinnamon can reduce potential adverse effects of electromagnetic exposure. Forty female Wistar rats were subdivided into four groups; (1) a control group received 3 cc normal saline (0.9%) daily and was treated for 6 weeks, (2) a group exposed to ELF-EMF of 3 mT for 4 h/day 7 days/week for 6 weeks, (3) a group received Allium cepa and cinnamon (75 mg/kg body weight) daily for 6 weeks, (4) and a group exposed to ELF-EMF and received Allium cepa and cinnamon. On the 42nd day of research, 5 cc blood was collected from all the rats to measure serum malondialdehyde (MDA) levels, glutathione peroxidase (GPX), superoxide dismutase (SOD), and catalase (CAT). Right ovaries were removed and prepared for electron microscopy study. Level of MDA significantly increased in the second group exposed to ELF-EMF (P < 0.05) and decreased in groups that received of Allium cepa and cinnamon (75 mg/kg body weight) (P < 0.05) in comparison to the control group. As well, levels of SOD, GPX, and CAT, significantly decreased in the second group (P < 0.05) and increased in groups that received Allium cepa and cinnamon (P < 0.05). Using Allium cepa and cinnamon as a nutritional supplements has beneficial effects on protection of reproductive systems in this life area population exposed to electromagnetic field.
http://bit.ly/2tf0ckb
Impairment of neuro-renal cells on exposure to cosmopolitan polluted river water followed by differential protection of Launea taraxacifolia in male rats
Abstract
Neuron-nephron toxicity (NNT) has been associated with the development of Alzheimer's disease and mental disorders. We hypothesized that increased neuronal cholinesterase activities and oxidative stress play significant roles in kidney injury and that methanolic fraction from Launea taraxacifolia (LTME) could differentially promote brain-kidney wellness after sub-chronic exposure to metropolitan Surulere polluted river water (SPRW). The animals were divided into six groups (n = 8). Group I was orally given 1 ml of distilled water only; group II received 1 ml of SPRW only; group III (pre-treated) received 200 mg/kg LTME before + 1 ml of SPRW after; group IV (Co-treated) received 200 mg/kg LTME + 1 ml of SPRW; group V (post-treated) received 1 ml of SPRW before + 200 mg/kg LTME after; and group VI received 200 mg/kg LTME only. The experiment lasted for 28 days. Exposed animals to SPRW exhibited impairment to neuronal and nephritic cells with elevated cholinesterase activities and significant (p < 0.05) alteration in cerebral and renal antioxidants. There was also brain-kidney depletion in lactate dehydrogenase (LDH) activity. Differential treatment from LTME prevented the sub-chronic SPRW intoxication in brain-kidney of male rat. Conclusively, LTME differentially attenuates the key indicators of neuron-nephritis and restores the endogenous antioxidant molecules via reduction of AChE and BuChE activities.
http://bit.ly/2ULrYjG
Health status of indigenous and exotic chickens sold in live bird markets
Abstract
Live bird markets (LBMs) contain pool of various birds of different breeds, species, types, and ages, and from different sources and have been identified as impending cores of diseases' incubation and transmission. From the point of food safety concern, it is highly empirical to document the health status and possible disease invasion in such markets to control the market for disease-free chicken so as to ensure supply of safe food for the consumers. One hundred twenty birds comprising of exotic and indigenous breeds of cockerels and layers were surveyed in three LBMs within Abeokuta Metropolis, Ogun State, Nigeria, using a 2 × 2 × 3 factorial arrangement of breed, types of chickens, and market. Data were collected on pulse rate (PR), respiratory rate (RR), body temperature (BT) for vital signs; packed cell volume (PCV), hemoglobin (Hb), and red blood cell (RBC) for hematological indices; and basophil, eosinophil, neutrophil, lymphocytes, and heterophil-lymphocytes (H:L) ratio for white blood cell differentials (WBCD) and analyzed using ANOVA. Indigenous chickens and cockerels recorded highest (p < 0.05) PR (224.5 bpm and 224.63 bpm, respectively). Market had significant (p < 0.05) influence on RR and BT of the chickens. Chicken types had no significant (p > 0.05) influence on PCV, RBC, and Hb while breed influenced (p < 0.05) the RBC. Market had significant influence on all the hematological parameters. Breed and chicken types significantly (p < 0.05) influenced white blood cell differentials. Indigenous breed of chickens had the highest (p < 0.05) eosinophil (1.67%), neutrophil (35.83%), lymphocyte (58.00%), monocyte (4.5%), and H:L (0.71), while cockerels recorded highest (p < 0.05) of 1.5%, 38.23%, 56.13%, 4.13%, and 0.77%, respectively, for these parameters. The study concluded that breed and types of chickens had significant influence on vital signs. Also, market had influence on RR, BT, hematology, neutrophil, and H:L ratio of the birds sold at LBMs. Therefore, markets should be controlled for the right breed and type of chickens for the supply and consumption of healthy chicken and chicken products (meat and egg).
http://bit.ly/2tnkZ5b
Students Introduce the 2019 Marquette Challenge
Marquette Challenge student coordinators kick off the 2019 campaign at CSM
https://www.youtube.com/watch?v=PxsCS9W6oV4
"J BUON"[jour]; +24 new citations
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http://bit.ly/2BsemTu
#APTACSM: Education, Inspiration, Community
APTA's Combined Sections Meeting is the biggest physical therapy conference in the country! Thanks to the nearly 17,000 people who attended #APTACSM 2019 in Washington, DC!
https://www.youtube.com/watch?v=ve4b9HnJQSI
The White House PT
PT for former President Barack Obama on what a typical day was like.
https://www.youtube.com/watch?v=qP2kvp14D34
Entrepreneurship in Physical Therapy
The founders of PhysioU discuss the evolution of their app, their growth as entrepreneurs and more!
https://www.youtube.com/watch?v=65qISPnK2Kk
How To Know If A Residency Is For You
APTA staff expert on residencies gives insight on how to know if you're the best fit for a residency.
https://www.youtube.com/watch?v=71sJTe0Jsxs
APTA’s 2019-2020 Public Policy Priorities
APTA vice president Matt Hyland, PT, PhD, MPA, discusses APTA's newly released public policy priorities for 2019-2020.
https://www.youtube.com/watch?v=h0jiAswNpYo
People With Parkinson Disease Keep Moving Through Telerehabilitation
PTJ editor in chief Alan Jette, PT, PhD, and Terry Ellis, PT, PhD, Board-Certified Clinical Specialist in Neurologic Physical Therapy, discuss the effectiveness of rehab and exercise interventions in modifying the progress of disease and disability in people with Parkinson disease, including the use of mobile health technologies and soft robotic systems.
https://www.youtube.com/watch?v=1PbhE4VfK_c
Getting Involved as a Student, You Won't Regret It
One student speaking for many on how student involvement changed his student experience and professional trajectory.
http://bit.ly/2TD2KUt
https://www.youtube.com/watch?v=tzhLN33HLxk
PT Licensure Compact: What Students Need To Know
We're talking about the PT Licensure Compact and what PTs and students need to know.
https://www.youtube.com/watch?v=QHsv2dBhvpU
Student Leaders On Involvement and Engagement
APTA Student Assembly Board members on the importance of student involvement.
http://bit.ly/2TD2KUt
https://www.youtube.com/watch?v=s7VbgO-xu-Y
Anxiety Diaries My Whole Body is a Nervous System
The struggle with anxiety, stress, and depression is real for some in PT and PTA school, but this student is here to tell you it gets better and you have a support system.
https://www.youtube.com/watch?v=7bzrQKuT6Vo
Changes to Payment for PTs
Particularly if you're in private practice, home health, or a skilled nursing facility, you need to be aware payment changes that have arrived or are just around the corner.
https://www.youtube.com/watch?v=vXjtidH5uP0
APTA Releases a New 3-Year Strategic Plan
APTA is approaching its centennial in 2021 and has a new, data-driven strategic plan to lead the way.
https://www.youtube.com/watch?v=8maIfzSkk6U
Cadmium in Groundwater Consumed in the Rural Areas of Gonabad and Bajestan, Iran: Occurrence and Health Risk Assessment
Abstract
Evidences show that high levels of cadmium intake may be contributing to a wide range of deleterious health effects. This study was performed to estimate the concentration of cadmium and the health risk to human by cadmium through the ingestion of groundwater in 39 rural areas of Gonabad and Bajestan, eastern Iran. The mean cadmium concentrations in groundwater in the studied rural areas of Gonabad and Bajestan ranged from 0.087 to 14.32 μg/L and from 0.417 to 18.36 μg/L, respectively. Health risk quotient for cadmium contamination for 16 and 38% of children and infants in rural areas of Gonabad and Bajestan, respectively, was more than 1 which causes non-carcinogenic risk to the local population. The carcinogenic risk of cadmium in drinking water for adults, children, and infants in 16, 33, and 33% of studied rural areas of Gonabad and Bajestan, respectively, was higher than the safe limit of 1.0 × 10−4. For rural areas of Bajestan, the cancer risk in 42, 52, and 52% of adults, children, and infants was above the safe limit. It was strongly suggested that the accessible procedures of treatment should be taken for a portion of contaminated rural areas before the distribution of the groundwater for the local population.
http://bit.ly/2ULVJkD
Genomic Characterization of the Zinc Transcriptional Regulatory Element Reveals Potential Functional Roles of ZNF658
Abstract
The zinc transcriptional regulatory element (ZTRE) is a newly reported binding motif for human zinc finger protein ZNF658, which alters gene expression in response to cellular zinc. The ZTRE has two nucleotide components—the palindromic flanking pairs and the bridging "N" bases between these flanks that range in number from 0 to 100. There are 12 pairs of ZTRE flanks (designated A-L). Three thousand five hundred twenty-five genes contain one or more ZTREs − 1000 to + 200 bp from their transcriptional start site (TSS). ZTRE-E is observed at a greater frequency, and ZTRE containing 25 bridging bases are less frequent, within − 200 bp from the TSS. The genes with ZTREs in this range are enriched in processes that may compensate zinc deficiency, while other genes with ZTREs outside this range are enriched in transcriptional activation processes. The division of ZTREs into two groups may imply a dual role of ZNF658, similar to the homologous yeast protein Zap1, via binding to low or high affinity sequences dependent upon cellular zinc. The KLF/Sp1-family binding motif is prevalent within the ZTRE "N" bridging bases, suggesting ZNF658 may compete with Sp1-like transactivators to suppress transcription.
http://bit.ly/2WXg3l0
Dietary Intake of Cadmium, Chromium, Copper, Nickel, and Lead through the Consumption of Meat, Liver, and Kidney and Assessment of Human Health Risk in Birjand, Southeast of Iran
Abstract
This study aimed to evaluate the mean concentration of cadmium (Cd), chromium (Cr), copper (Cu), nickel (Ni), and lead (Pb) in the meat and offal of cow and sheep. Also, the estimated daily intake (EDI) and health risk of these metals were calculated. Analysis of metals was undertaken by the use of an inductively coupled plasma-optic emission spectroscopy (ICP-OES). All samples were contaminated with all metals. Principal component analysis (PCA) showed a clear differentiation of cow and sheep in both the kidney and liver samples. In the liver and kidney, level of Cd, Cu, and Pb were positively correlated. The highest target hazard quotients (THQs) were calculated for Pb. Cd level in cow kidney had the highest carcinogenic rate (CR). Although, hazard index (HI) was lower than one, consumption of muscle especially in children should be noticed in both national and international consumers due to higher level of HI.
http://bit.ly/2RJEfU3
Selenium Levels in Community Dwellers with Type 2 Diabetes Mellitus
Abstract
Selenium (Se) is an essential micronutrient required by the human body and exerts biological functions through selenoproteins. The relationship between Se and diabetes remains ambiguous. This study aimed at, through measurements of serum selenoprotein P (SelP), glutathione peroxidase (GPx3), and Se content in serum and hair, evaluating Se levels in community dwellers with type 2 diabetes mellitus (T2DM). A total of 336 subjects, including 176 T2DM patients (65.5 ± 8.7 years old) and 160 healthy residents (63.7 ± 9.8 years old, as controls), were recruited in this cross-sectional community-based study performed in Suzhou. Samples of fasting venous blood and hair were collected for measurements of Se levels, glycometabolism, and biochemistry parameters. We found that the serum Se level and SelP concentration in T2DM patients were substantially higher than those in healthy residents (p < 0.05). There was no significant difference in GPx3 activity and hair Se level between the two groups of subjects (p > 0.05). Serum Se was positively correlated with both GPx3 and hair Se in T2DM patients (r = 0.167 and 0.164, respectively, p < 0.05) and negatively correlated with SelP in healthy controls (r = − 0.293, p < 0.05). In conclusion, this study showed significantly higher levels of serum Se and SelP in community dwellers with T2DM than in matched healthy residents.
http://bit.ly/2TxiVmk
Cadmium Exposure and Blood Telomere Length in Female University Students in Japan
Abstract
Cadmium is a toxic metal found ubiquitously throughout the world. Our study evaluated whether cadmium exposure was associated with telomere length in 73 female university students. Determination of telomere length was performed by quantitative polymerase chain reaction using DNA in blood. Urinary cadmium concentration was measured by inductively coupled plasma mass spectrometry. The students' physiological attributes and lifestyle were surveyed by means of a self-administered questionnaire. The geometric mean of urinary cadmium concentration was 0.312 μg/g creatinine, which was lower than the levels previously reported for Japan. Urinary cadmium concentration was not significantly associated with telomere length, though the exposure level of the present subjects was similar to that of previous study subjects which found significantly negative associations. It is possible that other factors affected telomere length in this study population.
http://bit.ly/2SruQFa
Is the Cooking Salt Safe in China? Assessment of Chemical Contaminants in Cooking Salt
Abstract
Global environmental pollution is becoming more serious, and most dietary salts come from nature. We postulated that chemical pollutants could affect the quality of salt. Forty-five different types of salt were collected from supermarkets, convenience stores, and online retailers in Shanghai, 2015. These comprised more than 90% of all cooking salts consumed in Shanghai, China. We measured and analyzed heavy metal elements, fluoride, potassium ferrocyanide, and 16 phthalate plasticizers. Lead was detected in only two types of salt at concentrations recorded of 0.047 mg/kg and 0.077 mg/kg. The concentrations of total arsenic, total mercury, cadmium, and barium were under limit of detection (LOD) in all samples. The maximum fluoride concentration of salts was 2.50 mg/kg. The median fluoride concentration of domestic salts was significantly lower than foreign-produced salts, and it was significantly higher in sea salt than in other types of salt (P < 0.05). The maximum potassium ferrocyanide concentration in 12 types of salts was 9.20 mg/kg, which was under the Chinese national standard. Just three salt types had low levels of diethylhexyl phthalate concentrations that were above the LOD, at 0.208 mg/kg, 0.375 mg/kg, and 0.380 mg/kg, respectively. All other phthalate indicators were below the LOD in all samples. The level of chemical pollutants in salt is either very low or under LOD. We believe that dietary salt products are safe at retail, and the long-term dietary exposure of cooking salts will not pose any significant health risk.
http://bit.ly/2REATli
High-Protein Diet Ameliorates Arsenic-Induced Oxidative Stress and Antagonizes Uterine Apoptosis in Rats
Abstract
Arsenic toxicity purportedly threats a broad spectrum of female reproductive functions. We investigated the remedial role of a casein- and pea protein-enriched high-protein diet (HPD) in combating the arsenic insult. Cyclic female rats maintained on standard diet (n = 6) or an isocaloric HPD (n = 6) were gavaged with As2O3 at 3 mg/kg BW/rat/day (n = 12) for 28 days. Vehicle-fed rats (n = 6) maintained on the standard diet served as the control. We monitored the estrus cycles and performed the histomorphometric analyses of the uterus and ovary. Uterine luminal epithelial (ULE) ultrastructure was appraised by scanning electron microscopy. Uterine oxidative stress was evaluated in the forms of ROS generation and activities of the ROS scavengers. The uterine apoptotic manifestation was blueprinted by Western blot analysis of caspase-3 and Bax expression. Arsenic treatment arrested the follicular maturation and disrupted the estrus cycles with a typical increase in the diestrus index. Shrunken endometrial glands and thinned microvilli density of the ULE reflected loss of cell polarity and mislaid uterine homeostasis. Increased ROS generation and attenuated activities of the ROS scavengers marked a state of uterine oxidative imbalance and loss of redox regulation. Superfluous expression of procaspase-3, cleaved caspase-3, and Bax mirrored an inflated state of uterine apoptosis. HPD supplementation, by and large, counteracted these arsenic impacts and maintained the frameworks close to the control levels. In conclusion, arsenic mediates its reproductive toxicity, at least in part, by upsetting the uterine ROS homeostasis and redox regulation. Pea proteins and casein-supplemented HPD can counteract the arsenic effects and maintain the reproductive functions.
http://bit.ly/2D9RFDF
Glutathione Might Attenuate Cadmium-Induced Liver Oxidative Stress and Hepatic Stellate Cell Activation
Abstract
The liver is a major organ involved in cadmium (Cd)-induced oxidative damage. Following liver injury, hepatic stellate cells (HSCs) are activated to participate in the wound healing process, but also facilitate liver fibrosis. Previous studies have observed fibrogenic effects of Cd on liver. However, the oxidative stress mechanisms of Cd-induced HSC activation as well as whether administration of glutathione (GSH) alleviates this activation, remain unclear. In this study, 24 rats were divided randomly into four experimental groups: control, GSH-treated, Cd-treated, and Cd + GSH-treated. After 4 weeks, the liver injury index, HSC-specific activation markers, oxidative stress-related antioxidants, and enzyme activities and signals were measured. Cd uptake and the generation of reactive oxygen species (ROS) in hepatocytes were detected by mass cytometry and fluorescence microscopy, respectively. Levels of aspartate aminotransferase, xanthine oxidase, γ-glutamyl transpeptidase, and α-smooth muscle actin (αSMA) were significantly increased in Cd-treated rats. Activated HSCs positive for αSMA expression and excess collagen deposition were detected in the Cd-treated group. In contrast, activities of the antioxidant enzymes superoxide dismutase, glutathione peroxidase, and catalase were reduced. Supplementation with GSH reversed some of the Cd-induced effects and increased the protein level of phosphorylated (p)-P65 while decreasing p-JNK. Pretreatment with GSH lowered Cd uptake and ROS generation in hepatocytes in vitro. These results indicate that administration of GSH was effective in attenuating Cd-induced oxidative stress via decreasing Cd uptake, restoring the activities of oxidative enzymes, activating NF-κB, inhibiting the JNK signaling pathway, and preventing excessive ROS generation and HSC activation.
http://bit.ly/2BmlT69
Lanthanum Chloride Impairs the Blood-Brain Barrier Integrity by Reduction of Junctional Proteins and Upregulation of MMP-9 in Rats
Abstract
Lanthanum could cause cognitive impairment in children and rodent animals. The normal blood-brain barrier (BBB) integrity is essential for protecting the brain from systemic toxins and maintaining the homeostasis for proper neuronal function. BBB dysfunction has been implicated as a potential mechanism of heavy metal-induced neurotoxicity. The present study was aimed to investigate effects of lanthanum on BBB integrity and endothelial junctional complexes in the cerebral cortex of young rats. Animals were exposed to lanthanum chloride (LaCl3) through drinking water under 0, 0.25, 0.5, and 1.0% concentrations from postnatal day 0 until 30 days after weaning. LaCl3-exposure increased BBB permeability, caused ultrastructure changes in cerebral capillaries, and reduced protein expression of claudin-5, occludin, and VE-cadherin. Due to the critical role of matrix metalloproteinases (MMPs) in BBB integrity, we further examined alterations in MMPs activity and expression. Enhanced gelatinase activity and upregulated MMP-9 expression were observed after LaCl3-exposure, concurrently with decreased expression of endogenous inhibitor tissue inhibitors of metalloproteinase (TIMP)-1. Taken together, this study demonstrated that postnatal lanthanum exposure caused leakage of BBB in young rats, partially attributed to upregulation of MMP-9 and reduction of junctional proteins expression.
http://bit.ly/2tgTDNX
Smoking Is Positively Associated with Antithyroperoxidase Antibodies and Antithyroglobulin Antibodies in Populations with Mildly Deficient Iodine Intake
Abstract
To evaluate the relationship between smoking and both antithyroperoxidase antibody (TPOAb) and antithyroglobulin antibody (TgAb) positivity in subjects from Panshan, Zhangwu, and Huanghua with mildly deficient, more than adequate, and excessive iodine intake, respectively. Smoking-related data were collected by questionnaire, and laboratory measurements of TPOAb, TgAb, and thyrotropin (TSH) were determined at baseline and follow-up. (1) A 1.48-fold increased risk of TPOAb positivity was found in smokers than in non-smokers after adjusting for confounders (age, sex, and areas) (OR[95% CI] = 1.48[1.12–1.95], p = 0.01). (2) Among female subjects, the prevalence of thyroid autoantibodies in smokers was increased than that in non-smokers in Panshan, Zhangwu, and Huanghua (TPOAb): 16.79 vs. 8.89%, 14.14 vs. 11.09%, 19.53 vs. 9.57%; TgAb 15.32 vs. 9.29%, 12.79 vs. 11.94%, 17.19 vs. 10.55%, respectively). The difference was significant in Panshan after adjusting for age. (3) Female long-term smokers (> 20 years) had an increased frequency of thyroid autoantibody positivity than non-smokers after adjusting for confounders (TPOAb OR[95% CI] = 1.60[1.10–2.34]; TgAb OR[95% CI] = 1.31[0.88–1.94]). (4) There was no difference in the incidence of thyroid autoantibodies among non-smokers, new smokers, and long-term smokers at follow-up. (5) TSH was greater in TPOAb-positive subjects than in seronegative smokers (1.56 vs. 1.20 mU/L, p < 0.001) and non-smokers (1.97 vs. 1.58 mU/L, p < 0.001). However, TSH was also greater in non-smokers than in smokers, regardless of whether subjects were positive (1.97 vs. 1.56 mU/L, p = 0.04) or negative (1.58 vs. 1.20 mU/L, p < 0.001) for TPOAb. Long-term smoking could increase the prevalence of thyroid autoantibodies in a population with mildly deficient iodine intake. TSH levels were lesser in smokers than in non-smokers and greater in subjects with thyroid autoantibody positivity than in seronegative subjects. The influence of smoking on TSH levels was independent of thyroid autoantibody levels.
http://bit.ly/2RLcI8L
The Effect of Maternal Supplementation of Zinc, Selenium, and Cobalt as Slow-Release Ruminal Bolus in Late Pregnancy on Some Blood Metabolites and Performance of Ewes and Their Lambs
Abstract
The aim of this study was to determine the effect of the supplementation of a slow-release bolus of zinc (Zn), selenium (Se), and cobalt (Co) at late gestation (6 week prepartum) on performance and some blood metabolites of Mehraban ewes and their lambs until weaning. Seventy pregnant ewes, 6 weeks prior to expected lambing, were randomly divided into two groups (35 heads each) including (1) control group and (2) slow-release bolus group. Blood samples of ewes were obtained on day 10 prepartum and 45 and 90 days postpartum, and milk samples were collected on day 45. Blood samples of lambs were collected on days 10, 45, and 90. Body weight at birth and weaning and average daily gain were higher and percentage of mortality and white muscle disease rate were lower in lambs whose mothers were given a bolus (P < 0.05). Slow-release bolus administration increased serum alkaline phosphatase and whole blood glutathione peroxidase activity, plasma concentrations of Zn, Se, and vitamin B12 in ewes and their lambs (P < 0.05). In addition, serum creatine phosphokinase activity of lambs whose mothers were given bolus was lower (P < 0.05). Serum concentration of T3 in bolus given ewes and their lambs was higher (P < 0.05) and serum T4 concentration was lower (P < 0.05). Zinc, Se, and vitamin B12 concentrations in milk were significantly higher in treated ewes (P < 0.05). Obtained results showed that maternal supplementation of zinc, selenium, and cobalt as slow-release ruminal bolus in late pregnancy improved some mineral status of ewes and their lambs until weaning and led to higher body weights of lambs at weaning.
http://bit.ly/2H5cp4w
Calcium Channels, Rho-Kinase, Protein Kinase-C, and Phospholipase-C Pathways Mediate Mercury Chloride-Induced Myometrial Contractions in Rats
Abstract
Adverse effects of mercury on female reproduction are reported; however, its effect on myogenic activity of uterus and mechanism thereof is obscure. Present study was undertaken to unravel the mechanistic pathways of mercuric chloride (HgCl2)-induced myometrial contraction in rats. Isometric tension in myometrial strips of rats following in vitro exposure to HgCl2 was recorded using data acquisition system-based physiograph. HgCl2 produced concentration-dependent (10 nM–100 μM) uterotonic effect which was significantly (p < 0.05) reduced in Ca2+-free solution and inhibited in the presence of nifedipine (1 μM), a L-type Ca2+ channel blocker, thus suggesting the importance of extracellular Ca2+ and its entry through L-type calcium channels in HgCl2-induced myometrial contractions in rats. Cumulative concentration-response curve of HgCl2 was significantly (p < 0.05) shifted towards right in the presence of Y-27632 (10 μM), a Rho-kinase inhibitor, suggesting the involvement of Ca2+-sensitization pathway in mediating HgCl2-induced myometrial contraction. HgCl2-induced myometrial contraction was also significantly (p < 0.05) inhibited in the presence of methoctramine or para-fluoro-hexahydro-siladifenidol, a selective M2 and M3 receptor antagonists, respectively, which evidently suggest that mercury also interacts with M2 and M3 muscarinic receptors to produce myometrial contractions. U-73122 and GF-109203X, the respective inhibitors of PLC and PKC-dependent pathways, downstream to the receptor activation, also significantly (p < 0.05) attenuated the uterotonic effect of HgCl2 on rat uterus. Taken together, present study evidently reveals that HgCl2 interacts with muscarinic receptors and activates calcium signaling cascades involving calcium channels, Rho-kinase, protein kinase-C, and phospholipase-C pathways to exert uterotonic effect in rats.
Graphical Abstract
http://bit.ly/2REt0An
Mineral and Trace Metal Concentrations in Seaweeds by Microwave-Assisted Digestion Method Followed by Quadrupole Inductively Coupled Plasma Mass Spectrometry
Abstract
This study reports the total concentrations of mineral and trace metals sodium, potassium, calcium, magnesium, phosphorus, iron, copper, zinc, and manganese in the seaweeds Padina tetrastromatica, Turbinaria ornate, Sargassum wightii, Sargassum swartzii, Gracilaria edulis, Ulva lactuca, Chaetomorpha antennina, and Halimeda opuntia collected from mandapam coastal regions, Southeast coast of India. Microwave-assisted digestion was used for sample preparation prior to mineral and trace metal analysis. Mineral and trace metal analyses were determined by inductively coupled plasma mass spectrometry. The ranges of concentrations of mineral and trace metals in algae were 27.04 ± 2.54–194.08 ± 2.36 mg/kg for manganese, 1.88 ± 0.10–121.5 ± 0.70 mg/kg for sodium, 6.5 ± 0.56–90.5 ± 2.12 mg/kg for magnesium, 59.07 ± 0.34–672 ± 2.82 mg/kg for potassium, 13.15 ± 2.08–135.13 ± 1.59 for sulfur, 0.003 ± 0.001–3.44 ± 0.13 mg/kg for cobalt, 0.39 ± 0.19–8.95 ± 0.38 mg/kg for copper, 0.72 ± 0.28–25.72 ± 0.39 mg/kg for zinc, and 6.01 ± 0.27–188.47 ± 1.92 mg/kg for iron.The results were evaluated statistically, and the significant difference was observed in the mean concentrations of all mineral and trace elements, except Co, Cu, and Zn, among the type of seaweeds.
http://bit.ly/2RLPNKC
Borax Supplementation Alleviates Hematotoxicity and DNA Damage in Rainbow Trout ( Oncorhynchus mykiss ) Exposed to Copper
Abstract
Heavy metals have harmful effects on health of both ecosystems and organisms to their accumulation ability. Copper (Cu) is an essential element for organism survival, but EPA considers Cu as a priority pollutant. On the other hand, boron has well-defined biological effects in living organisms including cytoprotection and genoprotection, although borax (BX) metabolism is poorly described in fish. Moreover, the effects of boron supplementation against Cu-induced hematotoxicity and DNA damage in aquatic organisms are still undetermined. Therefore, the main aim of this study was to provide an overview of the strategy for therapeutic potential of BX against Cu exposure in rainbow trout, Oncorhynchus mykiss. For this aim, fish were fed with different doses of BX and/or copper (1.25, 2.5, and 5 mg/kg of BX; 500 and 1000 mg/kg of Cu) for 21 days in pretreatment and combined treatment options. At the end of the treatments (pre and combined), the hematological index (total erythrocytes count (RBC), total leucocytes count (WBC), hemoglobin (Hb), hematocrit (Hct), total platelet count (PLT), mean cell hemoglobin concentration (MCHC), mean cell hemoglobin (MCH), mean cell volume (MCV)), oxidative DNA damage (8-hydroxy-2-deoxyguanosine (8-OHdG)), and nuclear abnormalities in blood samples of treated and untreated fish were investigated. The statistically significant (p < 0.05) and dose-dependent increases in hematological indices, 8-OH-dG level, and rates of nuclear abnormalities were observed after exposure to Cu in both treatment group fish as compared to untreated group. On the contrary, treatments with BX doses alone did not alter these hematological and DNA damage endpoints. Moreover, both pretreatment and combined treatments with BX significantly alleviated Cu-induced hematotoxicity and genotoxicity. In a conclusion, the obtained data firstly revealed that borax exhibited hematoprotective and genoprotective effects against copper-induced toxicity in fish.
http://bit.ly/2HikFOy
Association of Endothelial Function with Parental Hypertension in Normotensive-Obese African-American Women: A Pilot Study
Obese African-American (AA) women are at high risk of hypertension (HT) and cardiovascular disease (CVD). Flow-mediated dilation (FMD) and arterial augmentation index (AI) are measures of endothelial function and arterial stiffness. Whether endothelial function and arterial stiffness predict risk of HT or CVD in obese African-American women with, versus without, parental histories of HT and whether aerobic exercise is an effective countermeasure remain unclear. The capacity for FMD is partly heritable. Therefore, we tested the hypotheses that less FMD and greater AI may be found in normotensive-obese, young-adult (18-26 year-old) AA women with hypertensive parents (n=10) than in a matched control group with normotensive parents (n=10) and that a single bout of aerobic exercise improves both endothelial function and arterial stiffness, with less improvement in the women with hypertensive parents. We studied each subject while at rest, 20 min before and 20 min after, 30 min of aerobic exercise. The exercise-induced changes and parental hypertension-related differences in AI were not significant. The exercise increased FMD in both of the groups with no significant difference in magnitude between the women with hypertensive and normotensive parents. FMD was significantly less in the women with hypertensive parents than in the women with normotensive parents after, but not before, the exercise (mean ±95% confidence interval of 11.3 ± 4.9% vs. 15.6 ± 4.9%, P=0.05). These findings suggest that a 30-min bout of aerobic exercise may improve FMD and unmask endothelial dysfunction in normotensive-obese, young-adult AA women with parental histories of HT. Future studies should determine whether regular aerobic exercise protects obese AA women from the endothelial dysfunction associated with diabetes and prevents CVD in this high-risk population.
http://bit.ly/2HQ1fB1
Effect of Participation with Accompanying Household Member in the Complete Health Improvement Program in Appalachia
Intensive therapeutic lifestyle modification programs, such as the Complete Health Improvement Program (CHIP), reduce cardiovascular disease (CVD) risk factors. However, there are little data on how participation in CHIP with a household member can affect CVD biomarkers. This study focuses on the benefit of joint participation of household members in CHIP in order to have a better outcome in improving CVD risk factors compared with lone or individual participation. Data from 20 CHIP classes offered from 2011 to 2015 in Athens, Ohio, where each class was conducted over 2-4 months, consisting of 16-18 sessions, were collected. Body mass index (BMI), blood pressure, fasting glucose, and lipid profiles were measured before and near the completion of each class. A statistically significant greater reduction in BMI (p = 0.003) in those who attended with a household member compared to those who attended as individuals was found. CHIP has some effect on various CVD risk factors for those who attend intensive therapeutic lifestyle modification programs with an accompanying household member. Hence, encouragement of participation with a family member or a "buddy" may be prudent, especially if weight reduction is a key program participation goal. Further evaluation of the "buddy effect" involving both of those residing in the same household and those who do not but nevertheless provide mutual support is warranted.
http://bit.ly/2Tm2GZs
Telemedicine and Cardiology in the Elderly in France: Inventory of Experiments
Telemedicine is now in vogue, allowing through computer and communication tools to be deployed in the field of health, such as cardiology, area in which it has shown interest, in international studies. As the population ages, older people are increasingly concerned with this innovative practice. We take a look at telemedicine projects in France concerning the elderly, in the field of cardiology.
http://bit.ly/2HpL4Kr
Analysis of In Vitro Osteoblast Culture on Scaffolds for Future Bone Regeneration Purposes in Dentistry
One of the main focuses of tissue engineering is to search for tridimensional scaffold materials, complying with nature's properties for tissue regeneration. Determining material biocompatibility is a fundamental step in considering its use. Therefore, the purpose of this study was to analyze osteoblast cell adhesion and viability on different materials to determine which was more compatible for future bone regeneration. Tridimensional structures were fabricated with hydroxyapatite, collagen, and porous silica. The bovine bone was used as material control. Biocompatibility was determined by seeding primary osteoblasts on each tridimensional structure. Cellular morphology was assessed by SEM and viability through confocal microscopy. Osteoblast colonization was observed on all evaluated materials' surface, revealing they did not elicit osteoblast cytotoxicity. Analyses of four different materials studied with diverse compositions and characteristics showed that adhesiveness was best seen for HA and viability for collagen. In general, the results of this investigation suggest these materials can be used in combination, as scaffolds intended for bone regeneration in dental and medical fields.
http://bit.ly/2SoOH7Z
Antibacterial Activity of Coumarins and Carbazole Alkaloid from Roots of Clausena anisata
Clausena anisata is one of the medicinal plants used traditionally for treatment of parasitic infections, irritation (boils, ringworm, and eczema), flatworm infestations, influenza, abdominal cramps, and constipation. Phytochemical screening test of dichloromethane/methanol (1 : 1) roots extract revealed the presence of flavonoids, phytosterols, coumarins, phenols, alkaloids, tannins, terpenoids, and free reducing sugars and the absence of saponins. Silica gel column chromatographic separation of the dichloromethane/methanol (1 : 1) extract afforded a carbazole alkaloid derivative of heptazoline (1) and three coumarins (2–4), including the known coumarins imperatorin (3) and chalepin (4). Structures of the compounds were elucidated by spectroscopic techniques (IR, 1H NMR, 13C NMR, and DEPT-135). Antibacterial activity of the crude extracts and isolated compounds was screened using agar diffusion method against strains of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Bacillus substilis. The results of antibacterial test revealed derivative of heptaphylline (1) and imperatorin (3) exhibited comparable antibacterial activity against S. aureus and B. substilis (14 and 13 mm zone of inhibition, respectively) to that of ciprofloxacin (15 mm zone of inhibition) at a concentration of 20 µg/mL. Chalepin (4) revealed more antibacterial activity against B. substilis (16 mm zone of inhibition) compared to ciprofloxacin (15 mm).
http://bit.ly/2t6AM7X
Novelty of Bioengineered Iron Nanoparticles in Nanocoated Surgical Cotton: A Green Chemistry
The current focus of nanotechnology is to develop environmentally safe methodologies for the formulation of nanoparticles. The phytochemistry of Zingiber officinale inspired us to utilize it for the synthesis of iron nanoparticles. GC-MS analysis revealed the phytochemical profile of ginger. Out of 20 different chemicals, gingerol was found to be the most potent phytochemical with a retention time of 40.48 min. The present study reports a rapid synthesis method for the formation of iron nanoparticles and its potential efficacy as an antibacterial agent and an antioxidant. Because of its antibacterial property, ginger extract was used to coat surgical cotton. Synthesized ginger root iron nanoparticles (GR-FeNPs) were characterized by UV-visible spectroscopy, Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction analysis, and particle size analysis. XRD confirmed the crystalline structure of iron oxide nanoparticles as it showed the crystal plane (2 2 0), (3 1 1), (2 2 2), and (4 0 0). The particle size analyzer (PSA) showed the average size of the particles, 56.2 nm. The antimicrobial activity of the FeNPs was tested against different Gram-positive and Gram-negative bacteria. E. coli showed maximum inhibition as compared with the other organisms. Antioxidant activity proved the maximum rate of free radicals at 160 µg/mL produced by nanoparticles. In addition, the antimicrobial activity of nanocoated surgical cotton was evaluated on the first day and 30th day after coating, which clearly showed excellent growth inhibition of organisms, setting a new path in the field of medical microbiology. Hence, iron-nanocoated surgical cotton synthesized using green chemistry, which is antimicrobial and cost effective, might be economically helpful and provide insights to the medical field, replacing conventional wound healing treatments, for better prognosis.
http://bit.ly/2UTXaxx
Effect of “DXB-2030,” a Polyherbal Formulation, on Experimental Polycystic Ovary Syndrome Associated with Hyperandrogenism
The objective of the present study was to evaluate "DXB-2030," a polyherbal combination of Trigonella foenum-graecum, Aloe vera, Sphaeranthus indicus, Nardostachys jatamansi, and Symplocos racemosa extracts in an experimental model of testosterone propionate (TP), induced polycystic ovary syndrome (PCOS) in female rats. Thirty animals were divided into 3 groups of 10 each; group 1 served as normal control; group 2 was administered with TP and served as positive control; along with TP, group 3 was treated with "DXB-2030" at a dose of 100 mg/kg p.o., for 60 days. At the end of the study period, the animals were subjected for the estimation of serum testosterone levels, oral glucose tolerance test (OGTT), weight of the ovaries, estrous cycle, and histopathological evaluation. An in vitro assay on GLUT4 expression was carried out to understand the effect of "DXB-2030" on insulin resistance. Results showed that treatment with "DXB-2030" reversed the TP-induced changes by increasing the GLUT4 expression and decreasing the body weight, testosterone levels, AUC of glucose in OGTT, and the cystic follicles of the ovaries, thus indicating its beneficial effect in PCOS by ameliorating the metabolic dysfunction and reproductive impairment, which are the pathophysiological conditions associated with PCOS. From the results obtained, it can be concluded that "DXB-2030" was effective in the management of experimental PCOS and hence may be recommended in the treatment of PCOS.
http://bit.ly/2HQ1hc7
Allergic Airway-Induced Hypersensitivity Is Attenuated by Bergapten in Murine Models of Inflammation
Bergapten (5-methoxypsoralen, 5-MOP) is a plant-derived furocoumarin with demonstrated anti-inflammatory action. The present study investigated its effects on allergic inflammation in two related pathways of mast cell degranulation. Compound 48/80 and lipopolysaccharide (LPS) were used to activate the IgE-independent pathway while bovine serum albumin (BSA) was used as allergen for the IgE-dependent pathway. The modulatory effect of bergapten on mast cell degranulation, neutrophil extravasation, protein concentration, lung histopathology, and oxidative stress was assessed. Bergapten at 10, 30, and 100 μg/ml for 15 min stabilized mast cells in rat mesenteric tissue from disruption in vitro and when administered in vivo at 3, 10, and 30 mg kg−1 for 1 h protected mice from fatal anaphylaxis induced by compound 48/80. Similarly, treatment of LPS-challenged mice with bergapten (3, 10, and 30 mg kg−1) for 24 h significantly decreased neutrophil infiltration into bronchoalveolar lavage fluid, mean protein concentration, and inflammatory cell infiltration of pulmonary tissues when compared to the saline-treated LPS-challenged control. In addition, lung histology of the bergapten-treated LPS-challenged mice showed significantly less oedema, congestion, and alveolar septa thickening when compared to the saline-treated LPS-challenged disease control. LPS-induced oxidative stress was significantly reduced through increased tissue activities of catalase and superoxide dismutase and reduced malondialdehyde levels on treatment with bergapten. In the triple antigen-induced active anaphylaxis, daily administration of bergapten at 3, 10, and 30 mg kg−1 for 10 days, respectively, protected previously sensitized and challenged mice against anaphylactic shock. Overall, our study demonstrates the ability of bergapten to attenuate allergic airway-induced hypersensitivity in murine models of inflammation, suggesting its possible therapeutic benefit in this condition.
http://bit.ly/2UTX7ll
Role of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) in Cancer Prevention and Cancer Promotion
The nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed by medical practitioners in many clinical conditions for the symptomatic treatment of pain and fever. Due to their anti-inflammatory properties, these drugs have been investigated for their anticancer effects in numerous studies. This is because chronic inflammation has long been linked to carcinogenesis. As such, anti-inflammatory drugs are believed to play a role in cancer treatment and prevention. In the past few decades, research has shown that NSAIDs may decrease the risk of certain types of cancer. However, there is also a growing body of research that proves the contrary. Furthermore, NSAIDs are well known for many side effects, including some life-threatening ones. This review will discuss the relationship between chronic inflammation and cancer, the role of NSAIDs in cancer prevention and cancer promotion, and some of the potentially lethal side effects of these drugs.
http://bit.ly/2S145Ic
Antimutagenic and Synergistic Cytotoxic Effect of Cisplatin and Honey Bee Venom on 4T1 Invasive Mammary Carcinoma Cell Line
Introduction. Honey bee venom (HBV) has various biological activities such as the inhibitory effect on several types of cancer. Cisplatin is an old and potent drug to treat most of the cancers. Our aim in the present study was to determine antimutagenic and cytotoxic effects of HBV on mammary carcinoma, exclusively and in combination with cisplatin. Methods. In this study, 4T1 cell line was cultured in RPMI-1640 with 10% fetal bovine serum (FBS), at 37°C in humidified CO2 incubator. The cell viabilities were examined by the MTT assay. Also, HBV was screened for its antimutagenic activity via the Ames test. The results were assessed by SPSS software version 19 and one-way ANOVA method considering level of significance. Results. The results showed that 6 mg/ml of HBV, 20 μg/ml of cisplatin, and 6 mg/ml HBV with 10 μg/ml cisplatin could induce approximately 50% of 4T1 cell death. The concentration 7 mg/ml of HBV with of 62.76% inhibitory rate showed the highest antimutagenic activity in comparison with other treatment groups. Conclusions. The MTT assay demonstrated that HBV and cisplatin could cause cell death in a dose-dependent manner. The cytotoxic effect of cisplatin also promoted by HBV. Ames test outcomes indicated that HBV could act as a significant mutagenic agent. The antimutagenic activity of HBV was increased considerably in the presence of S9 mix. Therefore, our findings have revealed that HBV can enhance the cytotoxic effect of cisplatin drug and its cancer-preventing effects.
http://bit.ly/2Sh1LvK
Disease-Modifying Effects of Long-Term and Continuous Use of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) in Spondyloarthritis
Spondyloarthritis or spondyloarthropathy (SpA) is a group of related rheumatic disorders, which presents with axial and nonaxial features, affecting structures within the musculoskeletal system, as well as other bodily systems. Both pharmacological and nonpharmacological therapeutic options are available for SpA. For decades, nonsteroidal anti-inflammatory drugs (NSAIDs) have been used as the first-line drugs to treat the disease. Research has shown that other than pain relief, NSAIDs have disease-modifying effects in SpA. However, to achieve these effects, continuous and/or long-term NSAID use is usually required. This review will give an overview of SpA, discuss NSAIDs and their disease-modifying effects in SpA, and highlight some of the important adverse effects of long-term and continuous NSAID use, particularly those related to the gastrointestinal, renal, and cardiovascular systems.
http://bit.ly/2RlCBaV
Antipathogenic Potential of a Polyherbal Wound-Care Formulation (Herboheal) against Certain Wound-Infective Gram-Negative Bacteria
This study investigated antipathogenic efficacy of a polyherbal wound-healing formulation Herboheal against three multidrug-resistant strains of gram-negative bacterial pathogens associated with wound infections. Herboheal was evaluated for its quorum-modulatory potential against three different human-pathogenic bacteria, first in vitro through the broth dilution assay and then in vivo in the model host Caenorhabditis elegans. Herboheal at ≥0.1% v/v was able to inhibit (19–55%) in vitro production of quorum sensing-regulated pigments in all these bacteria and seemed to interfere with bacterial quorum sensing by acting as a signal-response inhibitor. This formulation could compromise haemolytic activity of all three bacteria by ∼18–69% and induced their catalase activity by ∼8–21%. Herboheal inhibited P. aeruginosa biofilm formation up to 40%, reduced surface hydrophobicity of P. aeruginosa cells by ∼9%, and also made them (25%) more susceptible to lysis by human serum. Antibiotic susceptibility of all three bacteria was modulated owing to pretreatment with Herboheal. Exposure of these test pathogens to Herboheal (≥0.025% v/v) effectively reduced their virulence towards the nematode Caenorhabditis elegans. Repeated subculturing of P. aeruginosa on the Herboheal-supplemented growth medium did not induce resistance to Herboheal in this mischievous pathogen, and this polyherbal extract was also found to exert a post-extract effect on P. aeruginosa, wherein virulence of the Herboheal-unexposed daughter cultures, of the Herboheal-exposed parent culture, was also found to be attenuated. Overall, this study indicates Herboheal formulation to be an effective antipathogenic preparation and validates its indicated traditional therapeutic use as a wound-care formulation.
http://bit.ly/2CL7u3s
Nutraceuticals Inspiring the Current Therapy for Lifestyle Diseases
Nutraceuticals are the pharmaceutically blended products that possess both nutritional as well as the medicinal value. Such a product is designed to improve the physical health, fight against day-to-day challenges such as stress, increase longevity, etc. Nowadays, emphasis is given to those herbs which are used as food and medicine due to its greater acceptance. Due to dynamic action, the popularity of nutraceuticals among people as well as healthcare providers has been increased over medicines and health supplements. This review documents herbs with a wide variety of therapeutic values such as immunity booster, antidiabetic, anticancer, antimicrobial, and gastroprotective. These herbs could be better options to formulate as nutraceuticals. Several nutraceuticals are described based on their availability as food, chemical nature, and mechanism of action.
http://bit.ly/2HaziU5
Vaccination Controversies: An Adult Case of Post-Vaccinal Acute Disseminated Encephalomyelitis
Acute disseminated encephalomyelitis is a rare inflammatory demyelinating multifocal disease of the central nervous system that typically occurs in children following vaccination or exanthematous viral infections and conveys an elevated risk of neurological sequelae unless promptly recognized and treated. We describe an adult case of acute disseminated encephalomyelitis following vaccination against Mumps, Measles and Rubella, presenting with fever and progressive neurological deficits which improved under systemic corticosteroid therapy. Considering the ongoing public debate regarding universal vaccination and the surge of previously controlled infectious diseases, we aim not only to underline the need for a rigorous assessment of vaccination safety on adult patients in order to prevent misguidance of public opinion, but also to alert clinicians for an early diagnosis of acute disseminated encephalomyelitis in these patients, the incidence of which we speculate may be rising.
http://bit.ly/2UMM2lS
Obtaining Informed Consent for Anesthesia in Elective Surgery at a Tertiary-Care Hospital: Practices and Ethical-Legal Context
Introduction: Informed consent is an active process of the doctor-patient relationship, based on ethical and legal principles. The anesthetic act has inherent risks, which should be subject of specific consent. The aim of this study was to evaluate the degree of implementation of written specific informed consent for anesthesia in the context of elective surgery.
Material and Methods: An observational prospective study, at a tertiary university hospital, in 230 patients aged 60 years or older, undergoing elective surgery between May and July 2017. Eligible patients who consented to participate were interviewed clinically on the day before surgery. In the postoperative period, the anesthetic technique and the existence of the written informed consent for the anesthetic and surgical procedures were assessed. Patients who were unable to give informed consent or those admitted in the Intensive Care Unit after surgery were excluded.
Results: Written informed consent for the surgical procedure was obtained for 225 (97.8%), while it was obtained in just 96 (41.7%) patients for the anesthetic act. There was a higher prevalence of stroke, anemia, and higher Charlson and physical American Society of Anesthesiologists scores in patients without written informed consent for the anesthetic act.
Discussion: We identified a low implementation of written informed consent for anesthesia. This situation may have important implications in the context of disciplinary, civil or criminal liability.
Conclusion: Despite its importance, the practice of written informed consent for anesthesia in this institution is not yet implemented on a regular basis.
http://bit.ly/2tfBDUg
Multimorbidity and Disease Severity Measured by the Charlson Index in Portuguese Hospitalised Patients During the Year 2015: A Cross-Sectional Study
Introduction: The association between multimorbidity and disease severity is not well established. The objectives were to characterise multimorbidity and determine disease severity (trough Charlson), as well as to verify if there is an association between the number and type of disease and the Charlson index.
Material and Methods: A cross-sectional study based on exported data from the Portuguese National Health Service hospitalisations database, during the year 2015. The study included 22 chronic health conditions: 15 predicted in the Charlson index and seven frequent conditions (hypertension, obesity, dyslipidaemia, osteoarthritis, osteoporosis, anxiety and depression). The analysis was performed through the generalised linear model, considering binary logistic regression. In the analysis, the IBM SPSS version 24.0 tool was used.
Results: The study analysed 800 376 hospitalisations, from which 42% correspond to males. The average age of the sample was 59.8 years, being higher in men (62.3 years). The mean number of problems per person was 1.6, greater in men (1.8). Disease severity was also higher in males. The worst prognosis was associated with six or more conditions per person. The largest predictor of disease severity was the number of problems, followed by dementia and diabetes.
Discussion: The results seem to confirm the gender difference regarding morbidity pattern. The number of conditions per person was the greatest predictor of disease severity, particularly the presence of six or more conditions per person.
Conclusion: The major limitation was the use of the same medical conditions to measure multimorbidity and disease severity. Other studies and analysis models should explore the complexity of the multimorbidity phenomenon.
http://bit.ly/2tevjfu
Schizophrenia: What Non-Psychiatrist Physicians Need to Know
Schizophrenia is a disabling and severe mental illness that affects all social classes and racial and ethnic groups, spreading across every part of the world. It's more frequent in males and it usually manifests itself in late adolescence or early adulthood and its early detection by all clinicians is important so that there is a proper referral to specialized psychiatric care. This article intends to update the knowledge regarding the diagnosis, treatment and prognosis of schizophrenia, with an emphasis on the warning signs for a timely referral to psychiatric evaluation. We conducted a literature search across through articles available in databases of scientific articles but also in scientific and technical books specialized in the field of schizophrenia. The clinical presentation of this illness is heterogeneous and complex, with a typical evolution based on several episodes of acute decompensation requiring hospitalization. The diagnosis of schizophrenia relies on some key symptoms, and the various international diagnostic criteria vary in relation to the temporal window with productive symptomatology required to establish a diagnosis. The prognosis is variable, not always deteriorating and is all the better when the treatment is started as early as possible. Treatment requires a multidisciplinary approach and is based primarily on antipsychotic drugs. This medication although very effective for the typical symptoms of this illness, entails some adverse effects with medical consequences that are important in the clinical practice of all doctors of other specialties.
http://bit.ly/2tfSuWY
Medical Student Secrecy, its Link to the Duty of Confidentiality and the Right to Access and Reuse Health Information
The authors address the legal void that exists regarding medical student access to clinical records and health information that local healthcare organizations hold under legal and institutional custody. They develop a legal thesis that configures the creation of medical student professional secrecy and its connection with the duty of confidentiality as assumptions that underlie the medical student's right to access and reuse health information. Medical students have the legitimacy to access health information and clinical records, as they bear an unequivocal informational, legitimate, constitutionally protected and sufficiently relevant need. They conclude that the legislature must work together with universities and hospital institutions to legally establish the concept of Medical Student Professional Secrecy, its link to the duty of confidentiality and the right of the medical student to access and reuse health information. Furthermore, it must do so in a specific legal act and in the precise terms of the text approved unanimously by the Council of Portuguese Medical Schools, by the National Council of Medical Ethics and Deontology, by the National Council of the Portuguese Medical Association and by its President.
http://bit.ly/2UMLSLi
My Diabetes My Way: supporting online diabetes self-management: progress and analysis from 2016
My Diabetes My Way (MDMW) is the National Health Service (NHS) Scotland website for people with diabetes and their carers. It consists of an interactive information website and an electronic personal health re...
http://bit.ly/2E1u8q6
Evaluation of some neuropharmacological effects of Caladium bicolor aiton (araceae) leaf extracts in mice
Abstract
Caladium bicolor Aiton (Araceae) is used in ethnomedicine for the treatment of boils, wound ulcers and convulsion. This study investigated the effects of the leaf extracts on some neuropharmacological parameters. The leaves were collected, dried, powdered and then extracted by maceration in methanol to yield the whole extract (WE). Extraction was also done using n-hexane, ethyl acetate and methanol in a Soxhlet apparatus to obtain n-hexane (HE), ethyl acetate (EA) and methanol (ME) extracts. Preliminary phytochemical screening was done using the whole extract. Some neuropharmacological evaluations were carried out using standard methods. Phytochemical screening revealed the presence of carbohydrates, proteins, alkaloids and flavonoids. WE showed varying levels of protection against strychnine-induced convulsion. Each of HE, EA and ME increased latency (P < 0.01) to pentylenetetrazole-induced convulsion and offered varying levels of protection against maximal electroshock-induced seizure. Each of WE, HE and ME significantly increased the duration of stay on the open arm of the elevated plus maze. Both EA and ME at doses of 100 and 200 mg/kg, and HE at a dose of 400 mg/kg significantly reduced the duration of immobility in forced swim test. It is concluded that the leaf extracts possess anticonvulsant, anxiolytic and antidepressant properties.
http://bit.ly/2GzVh4U
A possible biomarker of neurocytolysis in infantile gangliosidoses: aspartate transaminase
Abstract
Gangliosidoses (GM1 and GM2 gangliosidosis) are rare, autosomal recessive progressive neurodegenerative lysosomal storage disorders caused by defects in the degradation of glycosphingolipids. We aimed to investigate clinical, biochemical and molecular genetic spectrum of Turkish patients with infantile gangliosidoses and examined the potential role of serum aspartate transaminase levels as a biomarker. We confirmed the diagnosis of GM1 and GM2 gangliosidosis based on clinical findings with specific enzyme and/or molecular analyses. We retrospectively reviewed serum aspartate transaminase levels of patients with other biochemical parameters. Serum aspartate transaminase level was elevated in all GM1 and GM2 gangliosidosis patients in whom the test was performed, along with normal alanine transaminase. Aspartate transaminase can be a biochemical diagnostic clue for infantile gangliosidoses. It might be a simple but important biomarker for diagnosis, follow up, prognosis and monitoring of the response for the future therapies in these patients.
http://bit.ly/2E0YPf9
Oxidative stress among L-2-hydroxyglutaric aciduria disease patients: evaluation of dynamic thiol/disulfide homeostasis
Abstract
L-2-hydroxyglutaric aciduria (L2HGA) is an autosomal recessive disorder that is caused by deficiency of 2-hydroxyglutarate dehydrogenase. Pathophysiology of brain damage is poorly understood. In recent years, it was proposed that oxidative stress was elevated and led to brain injury. Aim of this study is to evaluate thiol/disulphide homeostasis as an indicator of oxidative stress in L2HGA patients who have been receiving antioxidant treatment. Sixteen L2HGA patients and 16 healthy individuals were included in the study. All the L2HGA patients were regularly followed up and presented neurological dysfunction at different grades. Fourteen patients had been receiving antioxidant treatment. Serum native thiol (-SH), total thiol (-SH + -S-S-) and disulphide (-S-S) levels were measured. Disulphide/native thiol, disulphide/total thiol and native thiol/total thiol ratios were calculated from these values. No significant difference was observed in -SH, -SH + -S-S-, -S-S levels between two groups. In addition to that, no increase of disulphide/native thiol and disulphide/total thiol ratios was detected. Thiol/disulphide homeostasis parameters were also compared between patients who had been receiving and not receiving antioxidant therapy; and between different types of antioxidant therapy and the results did not point to any significant difference. This is the first study that evaluates dynamic thiol/disulphide homeostasis as an indicator of oxidative stress in L2HGA and it has one of the largest sample sizes among previous studies. In our study we suggest that antioxidant therapy should be effective in preventing oxidative stress in L2HGA patients, which has been reported in previous studies and should be a part of standard therapy.
http://bit.ly/2GAgtIk
Role of PUMA in the methamphetamine-induced migration of microglia
Abstract
In this study, we demonstrated that PUMA was involved in the microglial migration induced by methamphetamine. PUMA expression was examined by western blotting and immunofluorescence staining. BV2 and HAPI cells were pretreated with a sigma-1R antagonist and extracellular signal-regulated kinase (ERK), mitogen-activated protein kinase (MAPK), c-Jun N-terminal protein kinase (JNK), and phosphatidylinositol-3 kinase (PI3K)/Akt inhibitors, and PUMA expression was detected by western blotting. The cell migration in BV2 and HAPI cells transfected with a lentivirus encoding red fluorescent protein (LV-RFP) was also examined using a wound-healing assay and nested matrix model and cell migration assay respectively. The molecular mechanisms of PUMA in microglial migration were validated using a siRNA approach. The exposure of BV2 and HAPI cells to methamphetamine increased the expression of PUMA, reactive oxygen species (ROS), the MAPK and PI3K/Akt pathways and the downstream transcription factor signal transducer and activator of transcription 3 (STAT3) pathways. PUMA knockdown in microglia transfected with PUMA siRNA attenuated the increased cell migration induced by methamphetamine, thereby implicating PUMA in the migration of BV2 and HAPI cells. This study demonstrated that methamphetamine-induced microglial migration involved PUMA up-regulation. Targeting PUMA could provide insights into the development of a potential therapeutic approach for the alleviation of microglia migration induced by methamphetamine.
http://bit.ly/2E12idj
Protective effects of Nesfatin-1 peptide on cerebral ischemia reperfusion injury via inhibition of neuronal cell death and enhancement of antioxidant defenses
Abstract
Nesfatin-1 is a novel peptide with anorexigenic and anti-hyperglycemic properties. According to previous studies, this multi-functional peptide protects dopaminergic cells against neurotoxicity via anti-apoptotic effects. In addition, Nesfatin-1 protects myocardial tissue after myocardial infarction via anti-inflammatory and anti-apoptotic mechanisms. In this study, we investigated the neuroprotective effects of nesfatin-1 against cerebral ischemia reperfusion injury in the CA1 area of hippocampus in rats. 56 male Wistar rats (240-270 g) were randomly selected and allocated into four groups: (1) sham, (2) nesfatin-1, (3) ischemia/reperfusion, (4) ischemia/reperfusion+nesfatin-1. Cerebral ischemia induced by the occlusion of the common carotid arteries for 20 min was followed by reperfusion. Saline as a vehicle and nesfatin-1 (20 μg/kg) were injected intraperitoneally (IP) at the start of cerebral reperfusion. Apoptotic and necrotic cell death was detected by TUNEL and Nissl staining. Malondialdehyde (MDA) and antioxidant enzymes (GSH and SOD) levels were measured by the ELISA method. The results showed that cerebral ischemia increased the apoptotic and necrotic cell death in the CA1 area of hippocampus, while, treatment with nesfatin-1significantly reduced apoptotic and necrotic cell death. Moreover, the MDA levels of the hippocampus in ischemic rats were higher, whereas in nesfatin-1-treated rats the MDA levels were decreased. Furthermore, the SOD and GSH levels in the ischemic rats were decreased, whilst in ischemic rats treated with nesfatin-1, the SOD and GSH levels were increased. This study for the first time found that nesfatin-1 treatment improves CA1 hippocampus injuries after cerebral ischemia through preventing neuronal cell death and enhancement of antioxidant defenses.
http://bit.ly/2Gzql4N
Neurochemical alterations following the exposure to di-n-butyl phthalate in rats
Abstract
Due to its ability to cross blood brain barrier and placenta, dibutyl phthalate (di-n-butyl phthalate, DBP) is expected to cause severe side effects to the central nervous system of animals and humans. A little data is available about the potential DBP neurotoxicity; therefore, this work was designed to investigate the brain tissue injury induced by DBP exposure. Forty Wister albino rats were allocated randomly into 4 groups (10 rats each). Group 1 served as control and the rats administered with physiological saline (0.9% NaCl) orally for 12 weeks. Groups 2, 3 and 4 were orally treated with DPB (100, 250 and 500 mg/kg) respectively for 12 weeks. DBP-intoxicated rats showed a disturbance in the oxidative status in cerebral cortex, striatum and brainstem, as represented by the elevated oxidants [malondialdehyde (MDA), nitric oxide (NO), 8-hydroxy-2-deoxyguanosine (8-OHdG)] and the decreased antioxidant molecules [reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR)]. DBP also enhanced a pro-inflammatory state through increasing the release of tumor necrosis factor- α (TNF-α) and interleukin-1β (IL-1β). The increase of these cytokines was associated with the increase of pro-apoptotic proteins [Bcl-2 associated X protein (Bax) and caspase-3] and the decrease of the anti-apoptotic protein, B cell lymphoma 2 (Bcl-2). In addition, the levels of norepinephrine (NE), dopamine (DA) and acetylcholine esterase (AChE) activity were decreased. This was accompanied by the alterations in the major excitatory and inhibitory amino acids neurotransmitters levels. The present findings indicated that DBP could exert its neuronal damage through oxidative stress, DNA oxidation, neuroinflammation, activation of apoptotic proteins and altering the monoaminergic, cholinergic and amino acids transmission.
http://bit.ly/2E1hUh0
Can a hypercholesterolemic diet change the basal brain electrical activity and during status epilepticus in rats?
Abstract
The brain is an organ rich in lipids, including cholesterol, in which these lipids are associated to structure and brain function. Thus alterations in lipid levels of diets may interfere in the brain electrical activity. Our aim was to evaluate the interference of hypercholesterolemic diets in the brain electrical activity in normal individuals and with epilepsy. Histological analysis and electrocorticograms (ECoG) were performed in animals fed with and without hypercholesterolemic diet before and during the status epilepticus induced by pilocarpine. The power spectrum of ECoG was used to estimate the contribution of different brain rhythms in ECoG signal. The animals submitted to the status epilepticus showed cell death, vacuolization with destructuration of the cell layers. Both animal groups, those with status epilepticus and status epilepticus with hypercholesterolemic diet, showed cellular lesions similar. The hyperlipid diet promoted increase of brain electrical activity, this was revealed by increase in the average power of beta wave (14–30 Hz) and decrease in the average power of the delta wave (0,5–4 Hz). This increase of brain electrical activity was even higher when the animals were fed a hypercholesterolemic diet and submitted to status epilepticus. Animals fed with hypercholesterolemic diet and submitted to status epilepticus presented a higher increase in brain excitability compared to control animals. We observed that hypercholesterolemic diet favored a greater severity of the status epilepticus.
http://bit.ly/2GxZExr
The metabolic alterations within the normal appearing brain in patients with Hashimoto’s thyroiditis are correlated with hormonal changes
Abstract
Hashimoto's thyroiditis (HT) is the most common autoimmune disease in humans usually associated with subsequent hypothyroidism. The purpose of the study was to assess metabolic alterations within the normal appearing brain in subjects with HT using MR spectroscopy (MRS) and to correlate MRS measurements with hormonal concentrations. Fifty-five HT patients (mean age 43.5 yrs) and 30 healthy controls (mean age 42.5 yrs) were examined with the use of a 1.5 T MR scanner. There were no signs of central nervous system involvement in the studied group. The MRS examinations were performed using the single voxel method. The voxels were placed in the left parietal white matter (PWM) and the posterior cingulate gyrus (PCG). The NAA/Cr, Cho/Cr, and mI/Cr ratios were calculated. The correlations between metabolite ratios and hormonal concentrations (TSH, fT3, fT4) as well as anti-TG and anti-TPO levels were also assessed. We found significantly (p < 0.05) decreased NAA/Cr ratios in PCG and PWM in HT subjects compared to the control group. There were no other significant differences in metabolite ratios. We observed significant positive correlations between the NAA/Cr ratio in PCG as well as the PWM and fT3 level. There was also a significant negative correlation between the Cho/Cr ratio in the PCG and fT4 level. MRS could be a sensitive biomarker capable of depicting early cerebral metabolic disturbances associated with HT. Our findings may indicate the reduction of neuronal activity within the normal appearing brain in patients with HT as well as suggesting that there is a possible biological association between thyroid dysfunction and cerebral metabolic changes.
http://bit.ly/2E1PaVi
Intracerebroventricular injection of resveratrol ameliorated Aβ-induced learning and cognitive decline in mice
Abstract
Resveratrol (RSV) is a natural plant polyphenol compound which consists in red grape skins and wine in general. Plenty of previous studies have shown that resveratrol has neuroprotective effects. The primary object of this research was to study the effects of RSV on improving the cognitive function and neurodegeneration in the mouse model of Alzheimer's disease induced by Aβ1–42, and the possible mechanism about targeting on Sirt1, which results in attenuating inflammatory response and mitochondrial dysfunction. We established the AD model of intracerebroventricular (i.c.v.) injection of Aβ1–42 and it was observed that the significant decrease in alternately of Y Maze and the quadrant dwell time percentage of Morris water maze test. Furthermore, there were significant upregulations of AMPK/ PGC-1α and downregulations of NF-κB/ IL-1β/ NLRP3 signaling pathways in the hippocampus and prefrontal cortex in AD mice. The treatments with RSV and Donepezil could significantly ameliorate all the behavioral and biochemical changes induced by Aβ1–42. It also noticeably improved the histopathological changes in the hippocampus and cortex. The results suggested that RSV might protect against cognitive deficits and neurodegeneration induced by Aβ1–42, and serve as a potential agent in treatment of AD.
http://bit.ly/2GETZ99
Diagnosis of covert hepatic encephalopathy: a multi-center study testing the utility of single versus combined testing
Abstract
Covert hepatic encephalopathy (CHE) affects cognition in a multidimensional fashion. Current guidelines recommend performing Psychometric Hepatic Encephalopathy Score (PHES) and a second test to diagnose CHE for multi-center trials. We aimed to determine if a two-test combination strategy improved CHE diagnosis agreement, and accuracy to predict overt hepatic encephalopathy (OHE), compared to single testing. Cirrhotic outpatients without baseline OHE performed PHES, Inhibitory Control Test (ICT), and Stroop EncephAlapp (StE) at three centers. Patients were followed for OHE development. Areas under the receiver operation characteristic curve (AUROC) were calculated. We included 437 patients (399 with follow-up data). CHE prevalence varied with testing strategy: PHES+ICT 18%, ICT + StE 25%, PHES+StE 29%, ICT 35%, PHES 37%, and StE 54%. Combination with best test agreement was PHES+StE (k = 0.34). Sixty patients (15%) developed OHE. Although CHE by StE showed the highest sensitivity to predict OHE, PHES and PHES+StE were more accurate at the expense of a lower sensitivity (55%, AUROC: 0.587; 36%, AUROC: 0.629; and 29%, AUROC: 0.623; respectively). PHES+ICT was the most specific (85%) but all strategies including ICT showed sensitivities in the 33–45% range. CHE diagnosis by PHES (HR = 1.79, p = 0.04), StE (HR = 1.69, p = 0.04), and PHES+StE (HR = 1.72, p = 0.04), were significant OHE predictors even when adjusted for prior OHE and MELD. Our results demonstrate that combined testing decreases CHE prevalence without improving the accuracy of OHE prediction. Testing with PHES or StE alone, or a PHES+StE combination, is equivalent to diagnose CHE and predict OHE development in a multi-center setting.
http://bit.ly/2E2mEmz
Determination of Minimal Residual Disease in Multiple Myeloma: Does It Matter?
Abstract
Purpose of Review
The ability to detect minimal residual disease (MRD) in myeloma has improved due to advances in flow cytometry and sequencing methodologies. Here, we evaluate recent clinical trial data and explore the current and future roles of MRD assessment in the context of clinical trial design and clinical practice.
Recent Findings
A review of recent phase III studies reveals that achievement of MRD negativity is associated with improved progression-free survival (PFS) and/or overall survival (OS). Treatment arms that are more effective from a PFS or overall response rate perspective are also associated with superior MRD negativity rates. The current standard MRD methodologies are limited by requiring bone marrow samples and refinement of methodologies that can detect disease outside of the bone marrow is needed.
Summary
Currently, MRD is a prognostic biomarker and further efforts are required to determine whether it can serve as a surrogate endpoint. The use of MRD status to guide treatment decisions is currently not recommended outside the confines of a clinical trial.
http://bit.ly/2BDtgXd
Industry’s Giant Leap Into Cellular Therapy: Catalyzing Chimeric Antigen Receptor T Cell (CAR-T) Immunotherapy
Abstract
Purpose of Review
We describe the significant technological leap from bench to bedside that was achieved through a strong academic-industry collaboration between dedicated clinicians and researchers at the University of Pennsylvania, the Children's Hospital of Philadelphia, and Novartis to commercialize the chimeric antigen receptor T cell (CAR-T) therapy tisagenlecleucel (CTL019; Kymriah®; Novartis Pharma AG, Basel, Switzerland).
Recent Findings
Tisagenlecleucel was the first CAR-T therapy and the first gene therapy to receive US Food and Drug Administration approval in 2017, with an initial indication for pediatric and young adult patients with relapsed or refractory (r/r) acute lymphoblastic leukemia, followed by approval in May 2018 for a second indication in adult patients with r/r diffuse large B cell lymphoma. Subsequent approvals in the European Union, Switzerland, and Canada soon followed.
Summary
The tisagenlecleucel success story represents the development and commercialization of a first-of-its-kind personalized cellular therapy with a manufacturing process that supports commercial production and ongoing global clinical trials in a growing number of countries.
http://bit.ly/2TIavZE
Immunotherapeutic Approaches for Multiple Myeloma: Where Are We Now?
Abstract
Purpose of Review
The treatment landscape for multiple myeloma has evolved rapidly with the availability of multiple new drugs; however, although patient survival has improved, the disease remains incurable. Multiple myeloma is characterized by the unregulated growth of malignant plasma cells accompanied by immune dysfunction as well as disrupted immune surveillance mechanisms. Here, we analyze clinical modalities, with a focus on monoclonal antibodies and adoptive cellular therapy that enhance patients' immune systems and overcome these defects.
Recent Findings
Early clinical trials with PD-1 inhibitors were promising, but randomized phase III trials with immunomodulatory drugs showed increased toxicities. Monoclonal antibodies targeting surface antigens led to substantial clinical efficiency in relapsed myeloma. Chimeric antigen receptor (CAR) T cell therapy for multiple myeloma represents a significant advance, as exciting and dramatic responses in early clinical trials have been seen.
Summary
Immunotherapeutic approaches are promising and can augment or replace the current standard of care, with the potential to offer extended survival for myeloma patients.
http://bit.ly/2BseWAK
Should Overall Survival Remain an Endpoint for Multiple Myeloma Trials?
Abstract
Purpose of Review
While the traditional gold standard for demonstrating clinical benefit of a therapy has been to show prolongation of overall survival (OS), there are multiple factors which can hinder the use of OS as a primary endpoint in randomized clinical trials (RCTs). Here, we analyze recent myeloma RCTs and evaluate the issues relevant to current and future myeloma RCT design.
Recent Findings
A review of recent phase III RCTs that led to approval of new agents/combinations reveals that none were designed with OS as the primary endpoint, but instead utilized time to progression (TTP) or progression-free survival (PFS). These studies illuminate the inherent difficulties of designing trials with the primary endpoint of OS/PFS in a disease characterized by increasingly prolonged survival times, availability of effective salvage therapies, and competing events such as co-morbid conditions.
Summary
Alternative primary endpoints other than OS or PFS need to be developed for future myeloma RCTs. Validated surrogate endpoints with novel clinical trial designs will help improve the feasibility of conducting comparative clinical trials in a timely manner.
http://bit.ly/2TFWj3h
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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Alimentary Pharmacology &Therapeutics, EarlyView. https://ift.tt/2qECBIJ
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
