Source:Journal of Oral and Maxillofacial Surgery, Volume 75, Issue 5
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Increased left ventricular mass (LVM) is an early precursor of target organ damage due to hypertension. Diminished parasympathetic cardiac control has been linked to both hypertension onset and left ventricular impairment; however, emerging evidence suggests that this pattern may be different in African Americans. The present study sought to determine if race impacts the relationship between parasympathetic cardiac control and LVM.
LVM was assessed via echocardiography in a sample (N = 148) of African American and White adults (Mean age = 33.20 ± 5.71) with normal or mildly elevated blood pressure. Parasympathetic cardiac control was assessed by a measure of high frequency heart rate variability (HF-HRV) determined from electrocardiographic (ECG) recordings during 5 min of rest.
In regression analysis, greater HF-HRV was associated with greater LVM among African Americans (P = 0.002), but was not related to LVM in Whites (P = 0.919).
These are the first data to demonstrate that race moderates the relationship between HRV and LVM and further suggest that race may be an important factor in the association between parasympathetic cardiac control and other CVD risk factors.
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Our aim is to gain insight into the mechanisms underlying the anti-atrophic effects of leucine, namely, the way that this amino acid can restrain the up-regulation of MuRF1 and Mafbx/Atrogin-1 in muscle atrophy. Male rats received dietary leucine supplementation for 1–3 days, during which time their hind limbs were immobilized. Our results showed that leucine inhibited Forkhead Box O3 (FoxO3a) translocation to cell nuclei. In addition, leucine was able to reverse the expected reduction of FoXO3a ubiquitination caused by immobilization. Unexpectedly, leucine promoted these effects independently of the Class I PI3K/Akt pathway. Vacuolar protein sorting 34 (VPS34; a Class III PI3K) was strongly localized in nuclei after immobilization and leucine supplementation was able to prevent this effect. In experiments on cultured primary myotubes, dexamethasone led to the localization of VPS34 in the nucleus. In addition, the pharmacological inhibition of VPS34 blocked VPS34 nuclear localization and impaired the protective effect of leucine upon myotube trophicity. Finally, the pharmacological inhibition of VPS34 in primary myotubes prevented the protective effects of leucine upon MuRF1 and Mafbx/Atrogin-1 gene expression. Autophagy-related target genes were not responsive to leucine. Thus, we demonstrate that the anti-atrophic effect of leucine is dependent upon FoxO3a suppression and VPS34 activity.
Previous studies have shown that adult rabbit left ventricular myocytes exhibit sex and regional differences in L-type calcium current (ICa-L) levels that contribute to increased susceptibility to arrhythmogenic early afterdepolarizations (EADs). We used patch clamp recordings from isolated adult male and female rabbit right ventricular myocytes to determine apex-base differences in ICa-L density, and mathematical modeling to examine ICa-L contribution to EAD formation. Current density measured at 0 mV in female base myocytes was 67% higher than male base myocytes and 55% higher than female apex myocytes. No differences were observed between male and female apex myocytes, male apex and base myocytes, or in the voltage dependences of ICa-L activation or inactivation. The role of estrogen was investigated using cultured adult female right ventricular base myocytes. After 2 days, 17β-estradiol (1 nm) produced a 65% increase in ICa-L density compared to untreated controls, suggesting an estrogen-induced up-regulation of ICa-L. Action potential (AP) simulations using a modified Luo-Rudy cardiomyocyte model found that increased ICa-L density, at the level observed in female base myocytes, resulted in longer duration APs, and when combined with a 50% reduction of the rapidly inactivating delayed rectifier potassium current conductance to model Long QT Syndrome Type 2 (LQT2), the AP was accompanied by one or more EADs. Thus we found higher levels of ICa-L in adult female right ventricle base myocytes and the upregulation of this current by estrogen. Simulations of LQT2 found that elevated ICa-L contributed to EAD genesis.
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Hypoxia leads to augmentation of late sodium current (INa.L) and cellular Na+ loading, increased reverse Na+-Ca2+ exchange current (reverse INCX) and intracellular Ca2+ loading in rabbit ventricular myocytes. The purpose of this study was to determine the intracellular signal transduction pathways involved in the modulation of INa.L during hypoxia in ventricular myocytes. Whole-cell and cell-attached patch clamp techniques were used to record INa.L, and the whole-cell mode was also used to record reverse INCX and to study intercellular signal transduction mechanisms that mediate the increased INa.L. Dual excitation fluorescence photomultiplier systems were used to record calcium transient in ventricular myocytes. Hypoxia caused increases of INa.L and reverse INCX. These increases were attenuated by KN-93 (an inhibitor of CaMKII), bisindolylmaleimide VI (BIM, an inhibitor of PKC) and BAPTA/AM (a Ca2+ chelator). KN-93, BIM and BAPTA/AM had no effect on INa.L in normoxia. In studies of KN-93, hypoxia alone increased the density of INa.L from −0.31 ± 0.02 pA/pF to −0.66 ± 0.03 pA/pF (n = 6, P < 0.01 vs control) and the density of reverse INCX from 1.02 ± 0.06 pA/pF to 1.91 ± 0.20 pA/pF (n = 7, P < 0.01 vs control) in rabbit ventricular myocytes. In the presence of 1 μm KN-93, the densities of INa.L and reverse INCX during hypoxia were significantly attenuated to −0.44 ± 0.03 pA/pF (n = 6, P < 0.01 vs hypoxia) and 1.36 ± 0.15 pA/pF (n = 7, P < 0.01 vs hypoxia), respectively. In studies of BIM, hypoxia increased INa.L from −0.30 ± 0.03 pA/pF to −0.60 ± 0.03 pA/pF (n = 6, P < 0.01 vs control), and reverse INCX from 0.91 ± 0.10 pA/pF to 1.71 ± 0.27 pA/pF (n = 6, P < 0.01 vs control). In the presence of 1 μm BIM, the densities of INa.L and reverse INCX during hypoxia were significantly attenuated to −0.48 ± 0.02 pA/pF (n = 6, P < 0.01 vs hypoxia) and 1.33 ± 0.21 pA/pF (n = 6, P < 0.01 vs hypoxia), respectively. In studies of BAPTA/AM, hypoxia increased INa.L from −0.26 ± 0.04 pA/pF to −0.63 ± 0.05 pA/pF (n = 6, P < 0.01 vs control) and reverse INCX from 0.86 ± 0.09 pA/pF to 1.68 ± 0.35 pA/pF (n = 6, P < 0.01 vs control). The effects of hypoxia on INa.L and reverse INCX were significantly attenuated in the presence of 1 mm BAPTA/AM to −0.39 ± 0.02 pA/pF (n = 6, P < 0.01 vs hypoxia) and 1.12 ± 0.27 pA/pF (n = 6, P < 0.01 vs hypoxia), respectively. Results of single channel studies showed that hypoxia apparently increased the mean open probability and mean open time of sodium channels. These effects were inhibited by either 1 μm KN-93 or 1 mm BAPTA/AM. The suppressant effects of drug interventions were reversed upon washout. In addition, KN-93, BIM and BAPTA/AM also reversed the enhanced diastolic Ca2+ concentration, and the attenuated amplitude of [Ca2+]i transient, maximal velocities of Ca2+ increase and Ca2+ decay by hypoxia. In summary, the findings suggest that CaMKII, PKC, and Ca2+ all participate in mediation of the effect of hypoxia to increase INa.L.
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Dilated cardiomyopathy (DCM) can be caused by mutations in sarcomeric and non-sarcomeric genes. In this study we defined the pathogenic effects of three DCM causing mutations: the sarcomeric mutations in genes encoding cardiac troponin I (TNNI3p.98truncation) and cardiac troponin T (TNNT2p.K217deletion; also known as the K210del) and the non-sarcomeric gene mutation encoding lamin A/C (LMNAp.R331Q).
We assessed sarcomeric protein expression and phosphorylation and contractile behaviour in single membrane-permeabilized cardiomyocytes in human left ventricular heart tissue. Exchange with recombinant troponin complex was used to establish the direct pathogenic effects of the mutations in TNNI3 and TNNT2.
The TNNI3p.98trunc and TNNT2p.K217del mutation showed reduced expression of troponin I to 39% and 51%, troponin T to 64% and 53% and troponin C to 73% and 97% of controls, respectively, and altered stoichiometry between the 3 cardiac troponin subunits. The TNNI3p.98trunc showed pure haploinsufficiency, increased Ca2+-sensitivity and impaired length-dependent activation. The TNNT2p.K217del mutation showed a significant increase in passive tension that was not due to changes in titin isoform composition or phosphorylation. Exchange with wildtype troponin complex corrected troponin protein levels to 83% of controls in the TNNI3p.98trunc sample. Moreover, upon exchange all functional deficits in the TNNI3p.98trunc and TNNT2p.K217del samples were normalized to control values confirming the pathogenic effects of the troponin mutations. The LMNAp.R331Q mutation resulted in reduced maximal force development due to disease remodelling. Our study shows that different gene mutations induce DCM via diverse cellular pathways.
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Based on electron and proton transfer events occurring in biological respiration, a mitochondria-based biocell is constructed by combining with artificial nanochannels. In this biocell, mitochondria transfer electrons to the working electrode and pump protons into the electrolyte through the tricarboxylic acid cycle. The nanochannels provide passages for protons to transport along the transmembrane concentration gradient to consume electrons on the counter electrode, forming a continuous and stable current. Furthermore, the proton transmembrane transport behavior could be modulated by regulating the permeability area and surface charge of nanochannels. A high-performance biocell is obtained when equipped with the optimized nanochannels, which produces a current of ≈3.1 mA cm−2, a maximum power of ≈0.91 mW cm−2, and a lifetime over 60 h. This respiratory-based biocell shows great potential for the efficient utilization of bioelectricity.
A respiration-based biocell employing mitochondria and polyethylene terephthalate (PET) nanochannels is constructed for current generation. Mitochondria serving as energy transducer produce electrons and protons, and PET nanochannels provide passages for protons to consume electrons, forming a continuous and stable current. Furthermore, output current could be improved by optimizing the permeability area and surface charge of nanochannels.
Currently, bioresorbable electronic devices are predominantly fabricated by complex and expensive vacuum-based integrated circuit (IC) processes. Here, a low-cost manufacturing approach for bioresorbable conductors on bioresorbable polymer substrates by evaporation–condensation-mediated laser printing and sintering of Zn nanoparticle is reported. Laser sintering of Zn nanoparticles has been technically difficult due to the surface oxide on nanoparticles. To circumvent the surface oxide, a novel approach is discovered to print and sinter Zn nanoparticle facilitated by evaporation–condensation in confined domains. The printing process can be performed on low-temperature substrates in ambient environment allowing easy integration on a roll-to-roll platform for economical manufacturing of bioresorbable electronics. The fabricated Zn conductors show excellent electrical conductivity (≈1.124 × 106 S m−1), mechanical durability, and water dissolvability. Successful demonstration of strain gauges confirms the potential application in various environmentally friendly sensors and circuits.
Low-cost bioresorbable conductors are fabricated by evaporation–condensation mediated laser printing and sintering of Zn nanoparticle. The fabricated Zn conductors on bioresorbable polymer substrate show excellent electrical conductivity (≈1.124 × 106 S m−1), mechanical durability, and water dissolvability. Successful demonstration of strain gauges confirms the potential application in various environmentally-friendly sensors and circuits.
The MXenes combining hydrophilic surface, metallic conductivity and rich surface chemistries represent a new family of 2D materials with widespread applications. However, their poor oxygen resistance causes a great loss of electronic properties and surface reactivity, which significantly inhibits the fabrication, the understanding of the chemical nature and full exploitation of the potential of MXene-based materials. Herein we report a facile carbon nanoplating strategy for efficiently stabilizing the MXenes against structural degradation caused by spontaneous oxidation, which provides a material platform for developing MXene-based materials with attractive structure and properties. Hierarchical MoS2/Ti3C2-MXene@C nanohybrids with excellent structural stability, electrical properties and strong interfacial coupling are fabricated by assembling carbon coated few-layered MoS2 nanoplates on carbon-stabilized Ti3C2 MXene, exhibiting exceptional performance for Li storage and hydrogen evolution reaction (HER). Remarkably, ultra-long cycle life of 3000 cycles with high capacities but extremely slow capacity loss of 0.0016% per cycle is achieved for Li storage at a very high rate of 20 A g−1. They are also highly active HER electrocatalyst with very positive onset potential, low overpotential and long-term stability in acidic solution. Superb properties highlight the great promise of MXene-based materials in cornerstone applications of energy storage and conversion.
A facile yet efficient strategy is developed for stabilizing metastable MXenes against oxidation-induced structural degradation and the fabrication of high-performance MXene-based nanohybrids. The great promise of MXene-based materials in cornerstone applications for energy storage and conversion is highlighted by using MoS2/Ti3C2-MXene@C nanohybrids as ultra-long life anode materials in Li-ion batteries and highly active electrocatalyst for hydrogen evolution.
The lung research field has pioneered the use of organoids for the study of cell-cell interactions.
The use of organoids for airway basal cells is routine. However, the development of organoids for the other regions of the lung is still in its infancy. Such cultures usually rely on cell-cell interactions between the stem cells and a putative niche cell for their growth and differentiation.
The use of co-culture organoid systems has facilitated the in vitro cultivation of previously inaccessible stem cell populations, providing a novel method for dissecting the molecular requirements of these cell-cell interactions. Future technology development will allow the growth of epithelial-only organoids in more defined media and also the introduction of specific non-epithelial cells for the study of cell interactions. These developments will require an improved understanding of the epithelial and non-epithelial cell types present in the lung and their lineage relationships.
An important question in systems biology is what role the underlying molecular mechanisms play in disease progression. The relationship between chronic pancreatitis and pancreatic cancer needs further exploration in a system view. We constructed the disease network based on gene expression data and protein-protein interaction. We proposed an approach to discover the underlying core network and molecular factors in the progression of pancreatic diseases, which contain stages of chronic pancreatitis and pancreatic cancer. The chronic pancreatitis and pancreatic cancer core network and key factors were revealed and then verified by gene set enrichment analysis of pathways and diseases. The key factors provide the microenvironment for tumor initiation and the change of gene expression level of key factors bridge chronic pancreatitis and pancreatic cancer. Some new candidate genes need further verification by experiments. Transcriptome profiling-based network analysis reveals the importance of chronic pancreatitis genes and pathways in pancreatic cancer development on a system level by computational method and they can be therapeutic targets.
There is little information about how hair diameter differences within the safe donor area. Thicker or thinner hair may be needed depending on the recipient area, hairline design, and surgical purpose.
Thirty-eight non-alopecic subjects (19 males and 19 females) were evaluated. The safe donor area was defined as the area contained within 28 cm from the horizontal plane of the upper border of the hair rim to the vertical line of the bilateral external acoustic meatus. Seven zones were defined starting 2 cm on each side (bilateral 4 cm) from the mid-occiput to the temporal side. The diameters of 10 randomly selected anagen hairs were measured from each of the seven zones.
The results showed significant differences in hair diameter by zone between males and females (P < 0.0001). In general, hair diameter tended to decrease from zone 3 to 7.
Our results suggest that safe donor areas between zones 4 and 7 could be useful for specific hair transplantation surgeries requiring thinner hair, such as eyebrows, eyelashes, and female hairline correction surgery, whereas hair from zones 1–3 could be more useful for those requiring thicker hair, such as male and female pattern hair loss. Our data could be clinically valuable for planning hair transplant surgery and choosing the most optimal donor region.
Untreated calciphylaxis is a fatal disease of intra- and extravascular calcification, most commonly presenting in end-stage renal disease (ESRD) patients. While early identification is critical for timely treatment, early-stage clinical and histopathological descriptions have not, to our knowledge, been elucidated. As early clinical recognition is essential to prompt definitive histopathological diagnosis, this study describes a range of clinical and histopathological manifestations of early-stage calciphylaxis.
Five patients with clinical photographs of lesions of early-phase calciphylaxis were chosen from a recent database of 101 patients. Their clinical histories were reviewed and correlated with their respective clinical and histopathological images of early-stage disease and progression of the disease.
Two of the five patients were identified early to have calciphylaxis and were promptly initiated on aggressive, multimodal therapy, resulting in complete resolution and remission of calciphylaxis. The other three patients were also recognized in early stages, one without renal disease, although the disease had progressed to more advanced stages associated with greater morbidity and mortality.
These cases demonstrate that calciphylaxis may be clinically misdiagnosed due to ill-defined presentations, particularly in the early stages without the characteristic features of livedo racemosa and ulceration. However, recognition in the early stages is critical to implement timely treatment. As such, definitively diagnostic skin biopsy should be considered early in suspected cases to confirm the diagnosis of calciphylaxis and ensure prompt management of this lethal disease.
Burning mouth syndrome (BMS) is a disorder characterized by chronic mouth pain in the absence of objective clinical abnormalities. Vitamin or mineral deficiencies may have a role in BMS, but data regarding the prevalence and relevance of hematinic deficiencies are conflicting. We aimed to determine the frequency of specific laboratory abnormalities in patients with BMS.
We retrospectively reviewed the results of screening blood tests in patients with BMS at our institution between January 2003 and December 2013.
Among 659 patients with BMS, the most common decreased values or deficiencies were vitamin D3 (15%), vitamin B2 (15%), vitamin B6 (5.7%), zinc (5.7%), vitamin B1 (5.3%), thyrotropin (TSH) (3.2%), vitamin B12 (0.8%), and folic acid (0.7%). Laboratory values for fasting blood glucose and TSH were increased in 23.7% and 5.2%, respectively.
In patients with symptoms of BMS, our results suggest it is reasonable to screen for fasting blood glucose, vitamin D (D2 and D3), vitamin B6, zinc, vitamin B1, and TSH. Deficiencies of vitamin B12 and folic acid were rare (<1% abnormal).
Linear nail growth rate is affected by various conditions, one of which is the level of blood flow. Our supposition was that topical minoxidil, which has vasodilatory properties, can increase the rate of nail growth. The aim of this study was to determine the impact of topical minoxidil on nail growth. A 5% topical minoxidil solution was applied twice daily to the fingernails of 32 participants. Two groups of 16 participants were randomly chosen. In one group, the applications were made to the right index and left ring fingernails, and, in the other, the left index and right ring fingernails. During each visit (weekly during the first month and every 2 weeks during the second month), the nail length of six fingernails (index, middle, and ring of both hands) was measured using a digital caliper. Beginning in the first week, the mean nail length of the treated nails was greater than that of nails in the untreated group with statistical significance. There were no systemic or cutaneous side effects. During the first month, the mean growth of the treated nails was 4.27 mm/month compared with 3.91 mm/month in the untreated nails (P = 0.003). These findings suggest that a 5% concentration of topical minoxidil can stimulate nail growth with increased growth beginning in the first week of application. The results may have important implications for the treatment of nail disorders; however, a comparable study involving participants with nail disorders is highly recommended.
Women's interests in bondage, discipline, dominance/submission, and sadism/masochism (BDSM) behaviors are one of the most poorly understood research topics, even though erotica novels—typically read by women—are increasingly including these activities. The present study explored potential links between women's engagement in BDSM behaviors, consumption of erotica literature, relationship communication and satisfaction, and overall well-being using a multi-study approach. Results from three exploratory studies using multiple methodologies revealed a positive association between erotica, BDSM behaviors, and physical satisfaction, but brought attention to the relatively little information available for women who are interested in practicing alternative sexual behaviors. Practical suggestions for social scientists and mental health professionals are provided.
The safety assessment process of chemicals requires information on their mutagenic potential. The experimental determination of mutagenicity of a large number of chemicals is tedious and time and cost intensive, thus compelling for alternative methods. We have established local and global QSAR models for discriminating low and high mutagenic compounds and predicting their mutagenic activity in a quantitative manner in Salmonella typhimurium (TA) bacterial strains (TA98 and TA100). The decision treeboost (DTB)-based classification QSAR models discriminated among two categories with accuracies of >96% and the regression QSAR models precisely predicted the mutagenic activity of diverse chemicals yielding high correlations (R 2) between the experimental and model-predicted values in the respective training (>0.96) and test (>0.94) sets. The test set root mean squared error (RMSE) and mean absolute error (MAE) values emphasized the usefulness of the developed models for predicting new compounds. Relevant structural features of diverse chemicals that were responsible and influence the mutagenic activity were identified. The applicability domains of the developed models were defined. The developed models can be used as tools for screening new chemicals for their mutagenicity assessment for regulatory purpose.
There is little information about how hair diameter differences within the safe donor area. Thicker or thinner hair may be needed depending on the recipient area, hairline design, and surgical purpose.
Thirty-eight non-alopecic subjects (19 males and 19 females) were evaluated. The safe donor area was defined as the area contained within 28 cm from the horizontal plane of the upper border of the hair rim to the vertical line of the bilateral external acoustic meatus. Seven zones were defined starting 2 cm on each side (bilateral 4 cm) from the mid-occiput to the temporal side. The diameters of 10 randomly selected anagen hairs were measured from each of the seven zones.
The results showed significant differences in hair diameter by zone between males and females (P < 0.0001). In general, hair diameter tended to decrease from zone 3 to 7.
Our results suggest that safe donor areas between zones 4 and 7 could be useful for specific hair transplantation surgeries requiring thinner hair, such as eyebrows, eyelashes, and female hairline correction surgery, whereas hair from zones 1–3 could be more useful for those requiring thicker hair, such as male and female pattern hair loss. Our data could be clinically valuable for planning hair transplant surgery and choosing the most optimal donor region.
Untreated calciphylaxis is a fatal disease of intra- and extravascular calcification, most commonly presenting in end-stage renal disease (ESRD) patients. While early identification is critical for timely treatment, early-stage clinical and histopathological descriptions have not, to our knowledge, been elucidated. As early clinical recognition is essential to prompt definitive histopathological diagnosis, this study describes a range of clinical and histopathological manifestations of early-stage calciphylaxis.
Five patients with clinical photographs of lesions of early-phase calciphylaxis were chosen from a recent database of 101 patients. Their clinical histories were reviewed and correlated with their respective clinical and histopathological images of early-stage disease and progression of the disease.
Two of the five patients were identified early to have calciphylaxis and were promptly initiated on aggressive, multimodal therapy, resulting in complete resolution and remission of calciphylaxis. The other three patients were also recognized in early stages, one without renal disease, although the disease had progressed to more advanced stages associated with greater morbidity and mortality.
These cases demonstrate that calciphylaxis may be clinically misdiagnosed due to ill-defined presentations, particularly in the early stages without the characteristic features of livedo racemosa and ulceration. However, recognition in the early stages is critical to implement timely treatment. As such, definitively diagnostic skin biopsy should be considered early in suspected cases to confirm the diagnosis of calciphylaxis and ensure prompt management of this lethal disease.
Linear nail growth rate is affected by various conditions, one of which is the level of blood flow. Our supposition was that topical minoxidil, which has vasodilatory properties, can increase the rate of nail growth. The aim of this study was to determine the impact of topical minoxidil on nail growth. A 5% topical minoxidil solution was applied twice daily to the fingernails of 32 participants. Two groups of 16 participants were randomly chosen. In one group, the applications were made to the right index and left ring fingernails, and, in the other, the left index and right ring fingernails. During each visit (weekly during the first month and every 2 weeks during the second month), the nail length of six fingernails (index, middle, and ring of both hands) was measured using a digital caliper. Beginning in the first week, the mean nail length of the treated nails was greater than that of nails in the untreated group with statistical significance. There were no systemic or cutaneous side effects. During the first month, the mean growth of the treated nails was 4.27 mm/month compared with 3.91 mm/month in the untreated nails (P = 0.003). These findings suggest that a 5% concentration of topical minoxidil can stimulate nail growth with increased growth beginning in the first week of application. The results may have important implications for the treatment of nail disorders; however, a comparable study involving participants with nail disorders is highly recommended.
Burning mouth syndrome (BMS) is a disorder characterized by chronic mouth pain in the absence of objective clinical abnormalities. Vitamin or mineral deficiencies may have a role in BMS, but data regarding the prevalence and relevance of hematinic deficiencies are conflicting. We aimed to determine the frequency of specific laboratory abnormalities in patients with BMS.
We retrospectively reviewed the results of screening blood tests in patients with BMS at our institution between January 2003 and December 2013.
Among 659 patients with BMS, the most common decreased values or deficiencies were vitamin D3 (15%), vitamin B2 (15%), vitamin B6 (5.7%), zinc (5.7%), vitamin B1 (5.3%), thyrotropin (TSH) (3.2%), vitamin B12 (0.8%), and folic acid (0.7%). Laboratory values for fasting blood glucose and TSH were increased in 23.7% and 5.2%, respectively.
In patients with symptoms of BMS, our results suggest it is reasonable to screen for fasting blood glucose, vitamin D (D2 and D3), vitamin B6, zinc, vitamin B1, and TSH. Deficiencies of vitamin B12 and folic acid were rare (<1% abnormal).
Black men in the United States have substantially higher prostate cancer incidence rates than the general population. The extent to which this incidence disparity is because prostate cancer is more prevalent, more aggressive, and/or more frequently diagnosed in black men is unknown.
The authors estimated 3 independently developed models of prostate cancer natural history in black men and in the general population using an updated reconstruction of prostate-specific antigen screening, based on the National Health Interview Survey in 2005 and on prostate cancer incidence data from the Surveillance, Epidemiology, and End Results program during 1975 through 2000. By using the estimated models, the natural history of prostate cancer was compared between black men and the general population.
The models projected that from 30% to 43% (range across models) of black men develop preclinical prostate cancer by age 85 years, a risk that is (relatively) 28% to 56% higher than that in the general population. Among men who had preclinical disease onset, black men had a similar risk of diagnosis (range, 35%-49%) compared with the general population (32%-44%), but their risk of progression to metastatic disease by the time of diagnosis was from 44% to 75% higher than that in the general population.
Prostate cancer incidence patterns implicate higher incidence of preclinical disease and higher risk of metastatic progression among black men. The findings suggest screening black men earlier than white men and support further research into the benefit-harm tradeoffs of more aggressive screening policies for black men. Cancer 2017. © 2017 American Cancer Society.
Evidence is accumulating that a "1-size-fits-all" screening approach to prostate cancer may not be what is most appropriate. Therefore, the use of personalized screening approaches in higher risk men, particularly black men, warrants further policy consideration. See also pages 000-000.
Meta-analytic data on the effect of coffee in prostate cancer risk are controversial. Caffeine as a bioactive compound of coffee has not yet been studied in deep in vitro. Our study aimed at evaluating in a population cohort the effect of Italian-style coffee consumption on prostate cancer risk and at investigating in vitro the potential antiproliferative and antimetastatic activity of caffeine on prostate cancer cell lines. 6,989 men of the Moli-sani cohort aged ≥50 years were followed for a mean of 4.24 ± 1.35 years and 100 new prostate cancer cases were identified. The European Prospective Investigation into Cancer and Nutrition-Food Frequency Questionnaire was used for the dietary assessment and the evaluation of Italian-style coffee consumption. Two human prostate cancer cell lines, PC-3 and DU145, were tested with increasing concentrations of caffeine, and their proliferative/metastatic features were evaluated. The newly diagnosed prostate cancer participants presented lower coffee consumption (60.1 ± 51.3 g/day) compared to the disease-free population (74.0 ± 51.7 g/day) (p < 0.05). Multiadjusted analysis showed that the subjects at highest consumption (>3 cups/day) had 53% lower prostate cancer risk as compared to participants at the lowest consumption (0–2 cups/day) (p = 0.02). Both human prostate cancer cell lines treated with caffeine showed a significant reduction in their proliferative and metastatic behaviors (p < 0.05). In conclusion, reduction by Italian-style coffee consumption of prostate cancer risk (>3 cups/day) was observed in epidemiological level. Caffeine appeared to exert both antiproliferative and antimetastatic activity on two prostate cancer cell lines, thus providing a cellular confirmation for the cohort study results.
IgG4-related disease (IgG4-RD) is a rare, chronic inflammatory condition that may involve nearly every organ system. Originally identified as a cause of autoimmune pancreatitis, its characteristic histological and clinical features have been found in a wide variety of inflammatory presentations, including the eye and orbit. Here we describe an example of a case of IgG4-RD initially presenting as scleritis and vitritis, with further progression to multifocal bilateral orbital involvement. Tissue biopsy of an orbital mass was highly characteristic of IgG4-RD histology and a rapid clinical response to corticosteroids was observed. This case highlights IgG4-RD as a rare cause of intraocular inflammation that may progress to involve the orbit.
Hybrid lesions (HLs) have elements of congenital pulmonary airway malformation and extrapulmonary sequestration (EPS) and belong to the congenital lung lesions. EPS usually arises in the thorax or the abdomen but rarely in the diaphragm. The preoperative diagnostic work-up based on chest radiograph, ultrasound (US) and CT often shows imprecise results. Therefore, the exact localisation of the lesion can only be ascertained intraoperatively. Here we present a patient, with an intradiaphragmatic HL, and demonstrate the difficulties of surgical decision making regarding the localisation of the lesion and discuss the value of minimal invasive surgery.
Description
We present the case of a 67-year-old woman with a 3-week history of dysphagia in the absence of any respiratory or constitutional symptoms. A lifelong non-smoker with no significant medical comorbidities, it was thought unusual that a routine chest radiograph (figure 1) demonstrated diffuse, small, irregular nodules throughout her lung fields. The diagnosis of primary lung adenocarcinoma was made on the basis of a CT-guided biopsy (figure 2). It is likely that this atypical presentation and radiological appearance of primary malignancy is related to the erosion of tumour into one of the pulmonary arteries thus disseminating the neoplasm throughout the lungs. The cause for the patient's symptoms was attributed to malignant involvement of the central nervous system.
Figure 1
Chest X-ray.
Figure 2
CT scan of the chest.
To distinguish between...
Small bowel diverticulosis of the jejunum and ileum is an uncommon finding with a prevalence rate of 0.2% to 1.3% at autopsy and 0.3% to 1.9% on small bowel studies. Diagnosis can be difficult because there are no pathognomonic features or clinical symptoms that are specific for small bowel diverticulosis. Though rare, it is critical to keep the possibility of small bowel diverticulosis in mind when evaluating cases of malabsorption, chronic abdominal pain, haemorrhage, perforation and intestinal obstruction, especially in patients with connective tissue disorders, a family history of diverticula and a personal history of colonic diverticulosis. Guidelines for the treatment of complicated small bowel diverticulosis are not clearly defined. However, the consensus in treatment is to do a small bowel resection with primary anastomosis. We report three interesting cases of jejunoileal diverticula that presented in an occult manner and later progressed to more emergent manifestations.
Sleep apnoea and respiratory difficulties are reported in adult-onset Alexander's disease (AOAD), an autosomal-dominant leukodystrophy that presents mainly with progressive ataxia. We demonstrate for the first time that the respiratory symptoms can result from association of palatal tremor with a similar tremor of laryngeal and respiratory muscles that interrupts normal inspiration and expiration.
A 60-year-old woman presented with progressive ataxia, palatal tremor and breathlessness. MRI revealed medullary atrophy, bilateral T2 hyperintensities in the dentate nuclei and hypertrophic olivary degeneration (HOD). AOAD was confirmed genetically with a positive glial fibrillary acidic protein (GFAP) mutation. Electrophysiological study revealed 1.5 Hz rhythmic laryngeal and respiratory muscle activity. Her respiratory symptoms were significantly improved at night with variable positive pressure ventilation.
This case illustrates that palatal tremor in AOAD, and potentially in other conditions, may be associated with treatable breathlessness due to a similar tremor of respiratory muscles.
IgG4-related disease (IgG4-RD) is a rare, chronic inflammatory condition that may involve nearly every organ system. Originally identified as a cause of autoimmune pancreatitis, its characteristic histological and clinical features have been found in a wide variety of inflammatory presentations, including the eye and orbit. Here we describe an example of a case of IgG4-RD initially presenting as scleritis and vitritis, with further progression to multifocal bilateral orbital involvement. Tissue biopsy of an orbital mass was highly characteristic of IgG4-RD histology and a rapid clinical response to corticosteroids was observed. This case highlights IgG4-RD as a rare cause of intraocular inflammation that may progress to involve the orbit.
Hybrid lesions (HLs) have elements of congenital pulmonary airway malformation and extrapulmonary sequestration (EPS) and belong to the congenital lung lesions. EPS usually arises in the thorax or the abdomen but rarely in the diaphragm. The preoperative diagnostic work-up based on chest radiograph, ultrasound (US) and CT often shows imprecise results. Therefore, the exact localisation of the lesion can only be ascertained intraoperatively. Here we present a patient, with an intradiaphragmatic HL, and demonstrate the difficulties of surgical decision making regarding the localisation of the lesion and discuss the value of minimal invasive surgery.
Description
We present the case of a 67-year-old woman with a 3-week history of dysphagia in the absence of any respiratory or constitutional symptoms. A lifelong non-smoker with no significant medical comorbidities, it was thought unusual that a routine chest radiograph (figure 1) demonstrated diffuse, small, irregular nodules throughout her lung fields. The diagnosis of primary lung adenocarcinoma was made on the basis of a CT-guided biopsy (figure 2). It is likely that this atypical presentation and radiological appearance of primary malignancy is related to the erosion of tumour into one of the pulmonary arteries thus disseminating the neoplasm throughout the lungs. The cause for the patient's symptoms was attributed to malignant involvement of the central nervous system.
Figure 1
Chest X-ray.
Figure 2
CT scan of the chest.
To distinguish between...
Small bowel diverticulosis of the jejunum and ileum is an uncommon finding with a prevalence rate of 0.2% to 1.3% at autopsy and 0.3% to 1.9% on small bowel studies. Diagnosis can be difficult because there are no pathognomonic features or clinical symptoms that are specific for small bowel diverticulosis. Though rare, it is critical to keep the possibility of small bowel diverticulosis in mind when evaluating cases of malabsorption, chronic abdominal pain, haemorrhage, perforation and intestinal obstruction, especially in patients with connective tissue disorders, a family history of diverticula and a personal history of colonic diverticulosis. Guidelines for the treatment of complicated small bowel diverticulosis are not clearly defined. However, the consensus in treatment is to do a small bowel resection with primary anastomosis. We report three interesting cases of jejunoileal diverticula that presented in an occult manner and later progressed to more emergent manifestations.
Sleep apnoea and respiratory difficulties are reported in adult-onset Alexander's disease (AOAD), an autosomal-dominant leukodystrophy that presents mainly with progressive ataxia. We demonstrate for the first time that the respiratory symptoms can result from association of palatal tremor with a similar tremor of laryngeal and respiratory muscles that interrupts normal inspiration and expiration.
A 60-year-old woman presented with progressive ataxia, palatal tremor and breathlessness. MRI revealed medullary atrophy, bilateral T2 hyperintensities in the dentate nuclei and hypertrophic olivary degeneration (HOD). AOAD was confirmed genetically with a positive glial fibrillary acidic protein (GFAP) mutation. Electrophysiological study revealed 1.5 Hz rhythmic laryngeal and respiratory muscle activity. Her respiratory symptoms were significantly improved at night with variable positive pressure ventilation.
This case illustrates that palatal tremor in AOAD, and potentially in other conditions, may be associated with treatable breathlessness due to a similar tremor of respiratory muscles.
To evaluate human papillomavirus (HPV) testing as a primary screening tool, we retrospectively analyzed data comparing (1) HPV testing to the algorithms of the ATHENA Study: (2) cytology alone, (3) cytology with ASCUS triage in women 25–29 and (4) cotesting ≥ 30 or (5) cotesting ≥ 25.
We retrospectively analyzed data from women tested with both cytology and HPV testing from 2010 to 2013. Cumulative risk (CR) for CIN3+ was calculated. Crude and verification bias adjusted (VBA) sensitivity, specificity, predictive values, likelihood ratios, colposcopy rate, and screening test numbers were compared.
About 15,173 women (25–95, 7.1% <30) had both HPV and cytological testing. Nearly 1,184 (8.4%) had biopsies. About 19.4% had positive cytology, 14.5% had positive HPV. HPV testing unassociated with ASCUS was requested in 40% of women <30, versus 84% ≥30, with similar HPV16/18 genotyping results (68% vs. 70%). 84 CIN3+ were detected with the following 3-year cumulative risk (CR) (95% confidence interval): HPV+/ASCUS+, 46% (32–66%), HPV+/NILM 30% (15–58%), HPV−/ASCUS+ 12% (6–23%), and HPV−/NILM 0.8% (0.2–3.6%). HPV had higher specificity 57% (54–60%) than cotesting ≥30 52% (49–55%). HPV sensitivity 78% (69–87%), positive 12.3% (9.8–15.3%), negative 97 (96–98%) predictive values, positive 1.8 (1.6–2.1) and negative likelihood ratios 0.6 (0.5-0.6), were not significantly different. Cotesting increased colposcopy rate and doubled testing per CIN3+ diagnosed. Conclusion: While HPV−/NILM cotesting results are associated with low CIN3+ risk, HPV testing had similar screening performance to cotesting and to cytology alone. Additionally, HPV testing and cytology incur false negatives in nonoverlapping subsets of patients.
EMT and Paramedics are responsible for providing basic/advanced life support care(s) for the sick, injured, traumatic and non-emergent patient. The EMT/Paramedic will work within their scope of practice and agency's protocols as directed by agency's medical director. Primary responsibilities This is a general overview of responsibilities. Assess nature of patient's illness and or mechanism ...
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Monosodium glutamate (MSG), a flavor enhancer in diets, causes cognitive impairment in humans. Exercise has been reported to protect against impairment of memory in humans. This study investigated if resistance exercise improves the performance of male and female rats treated with MSG in tests of memory and motor coordination. Wistar rats received MSG (4g kg day−1, s.c.) from post natal day 1 to 10. At postnatal day 60, the animals started a resistance exercise protocol in an 80° inclined vertical ladder apparatus and performed it during 7 weeks. Rats performed object recognition and location memory tests. Resistance exercise reduced impairment in motor coordination of male and female rats treated with MSG. Resistance exercise was effective against the decrease in exploratory preference in the long-term recognition memory (LTM) for novel objects of male rats treated with MSG. In MSG-treated female rats, resistance exercise was effective against the decrease in exploratory preference in the novel object location test (OLT). The exploratory preference of female rats in the LTM test was similar in all groups. The short-term memory was not altered by MSG or resistance exercise in male and female rats. This study demonstrates that MSG affected in a different way memory of male and female rats. Resistance exercise was effective against the decrease in recognition for male and in location memory for female rats treated with MSG. This report demonstrates the beneficial effects of resistance exercise against the prejudice of motor condition and impairment of memory induced by MSG in male and female rats.
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To investigate the toxic mechanism of hexavalent chromium Cr(VI) and search for an antidote for Cr(VI)-induced cytotoxicity, a study of mitochondrial dysfunction induced by Cr(VI) and cell survival by recovering mitochondrial function was performed. In the present study, we found that the gene expression of electron transfer flavoprotein dehydrogenase (ETFDH) was strongly downregulated by Cr(VI) exposure. The levels of coenzyme 10 (CoQ10) and mitochondrial biogenesis presented by mitochondrial mass and mitochondrial DNA copy number were also significantly reduced after Cr(VI) exposure. The subsequent, Cr(VI)-induced mitochondrial damage and apoptosis were characterized by reactive oxygen species (ROS) accumulation, caspase-3 and caspase-9 activation, decreased superoxide dismutase (SOD) and ATP production, increased methane dicarboxylic aldehyde (MDA) content, mitochondrial membrane depolarization and mitochondrial permeability transition pore (MPTP) opening, increased Ca2+ levels, Cyt c release, decreased Bcl-2 expression, and significantly elevated Bax expression. The Cr(VI)-induced deleterious changes were attenuated by pretreatment with CoQ10 in L-02 hepatocytes. These data suggest that Cr(VI) induces CoQ10 deficiency in L-02 hepatocytes, indicating that this deficiency may be a biomarker of mitochondrial dysfunction in Cr(VI) poisoning and that exogenous administration of CoQ10 may restore mitochondrial function and protect the liver from Cr(VI) exposure.
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Ustekinumab is approved for the treatment of psoriasis in adolescents and for the treatment of moderate to severe Crohn's disease (CD) in adults, but data are lacking in pediatric CD. We report a case of severe psoriasis induced by biotherapies in an adolescent with CD that improved after switching to ustekinumab (90 mg at weeks 0, 2, and 4 and then every 8 weeks). The patient had not experienced CD relapse after 1 year of follow-up. Ustekinumab can be an alternative therapy for psoriasis induced by biotherapies when conventional treatment fails and can maintain remission of CD.
Ustekinumab is approved for the treatment of psoriasis in adolescents and for the treatment of moderate to severe Crohn's disease (CD) in adults, but data are lacking in pediatric CD. We report a case of severe psoriasis induced by biotherapies in an adolescent with CD that improved after switching to ustekinumab (90 mg at weeks 0, 2, and 4 and then every 8 weeks). The patient had not experienced CD relapse after 1 year of follow-up. Ustekinumab can be an alternative therapy for psoriasis induced by biotherapies when conventional treatment fails and can maintain remission of CD.
Hyperammonemia induced by valproate (VPA) treatment may lead to several neurological and systemic symptoms as well as to seizure exacerbation. Gait instability and recurrent falls are rarely mentioned as symptoms, especially not as predominant ones.
We report five adult patients with frontal lobe epilepsy (FLE) who were treated with VPA and in whom a primary adverse effect was unstable gait and falls.
There were four males and one female patients with FLE, 25-42-year-old, three following epilepsy surgery. All of them were treated with antiepileptic drug polytherapy. Gait instability with falls was one of the principal sequelae of the treatment. Patients also exhibited mild encephalopathy (all patients) and flapping tremor (three patients) that developed following the addition of VPA (three patients) and with chronic VPA treatment (two patients). VPA levels were within the reference range. Serum ammonia levels were significantly elevated (291-407 μmole/L, normal 20-85) with normal or slightly elevated liver enzymes. VPA dose reduction or discontinuation led to the return of ammonia levels to normal and resolution of the clinical symptoms, including seizures, which disappeared in two patients and either decreased in frequency or became shorter in duration in the other three.
Gait instability due to hyperammonemia and VPA treatment is probably under-recognized in many patients. It can develop when the VPA levels are within the reference range and with normal or slightly elevated liver enzymes.
A key requirement for precision medicine is the accurate identification of patients that would respond to a specific treatment or those that represent a high-risk group, and a plethora of molecular biomarkers have been proposed for this purpose during the last decade. Their application in clinical settings, however, is not always straightforward due to relatively high costs of some tests, limited availability of the biological material and time, and procedural constraints. Hence, there is an increasing interest in constructing tissue-based surrogate biomarkers that could be applied with minimal overhead directly to histopathology images and which could be used for guiding the selection of eventual further molecular tests. In the context of colorectal cancer, we present a method for constructing a surrogate biomarker that is able to predict with high accuracy whether a sample belongs to the "BRAF-positive" group, a high-risk group comprising V600E BRAF mutants and BRAF-mutant-like tumors. Our model is trained to mimic the predictions of a 64-gene signature, the current definition of BRAF-positive group, thus effectively identifying histopathology image features that can be linked to a molecular score. Since the only required input is the routine histopathology image, the model can easily be integrated in the diagnostic workflow.
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A series of aminomethylene-phosphonate (AMP) analogues, 8-14, bearing one or two heterocyclic moieties (imidazolyl, pyridyl, and thiazolyl) on the aminomethylene group, were synthesized as potential Zn(II)-chelators. The complexes of analogues 8-14 with Zn(II)-ions were characterized by their stoichiometry, geometry, coordination-sites, acid-base equilibria, and stability constants. Analogues 8-14 form stable water-soluble 2:1 L:Zn(II) complexes, as established by Zn(II)-titration, monitored by UV and by ¹H- and ³¹P-NMR spectroscopy. Acidity and stability constants were established for each derivative by potentiometric pH-titrations. ML₂-type Zn(II)-complexes of AMP, bearing either an imidazolyl or pyridyl moiety, 8, 10 and, 12, exhibit high logβ values - 17.68, 16.92, and 16.65, respectively, while for the AMP-thiazolyl, 14, -Zn(II) complex, logβ is 12.53. Generally, ligands 9, 11, and 13, bearing two heterocyclic moieties, present higher logβ values (22.25, 21.00, and 18.28, respectively) vs. analogues bearing one heterocyclic moiety. Additionally, based on ¹H-,¹³C-, and ³¹P-NMR data, we propose a structure of AMP-(Im)₂-Zn(II) complex in solution, where the Zn(II)-coordination sites involve the phosphonate moiety and both imidazolyl rings of the two binding molecules, forming an octahedral geometry around the Zn(II)-ion. In summary, we propose a novel family of water-soluble high-affinity Zn(II)-chelators, in particular AMP-(Im)₂, forming the most stable complex (logβ 22).
Transcranial direct current stimulation (tDCS) produces sustained and diffuse current flow in the brain with effects that are state dependent and outlast stimulation. A mechanistic explanation for tDCS should capture these spatiotemporal features. It remains unclear how sustained DCS affects ongoing synaptic dynamics and how modulation of afferent inputs by diffuse stimulation changes synaptic activity at the target brain region. We tested the effect of acute DCS (10–20 V m−1 for 3–5 s) on synaptic dynamics with constant rate (5–40 Hz) and Poisson-distributed (4 Hz mean) trains of presynaptic inputs. Across tested frequencies, sustained synaptic activity was modulated by DCS with polarity-specific effects. Synaptic depression attenuates the sensitivity to DCS from 1.1% per V m−1 to 0.55%. DCS applied during synaptic activity facilitates cumulative neuromodulation, potentially reversing endogenous synaptic depression. We establish these effects are mediated by both postsynaptic membrane polarization and afferent axon fibre polarization, which boosts cooperativity between synaptic inputs. This potentially extends the locus of neuromodulation from the nominal target to afferent brain regions. Based on these results we hypothesized the polarization of afferent neurons in upstream brain regions may modulate activity in the target brain region during tDCS. A multiscale model of transcranial electrical stimulation including a finite element model of brain current flow, numerical simulations of neuronal activity, and a statistical theory of coincident activity predicts that the diffuse and weak profile of current flow can be advantageous. Thus, we propose that specifically because tDCS is diffuse, weak and sustained it can boost connectivity between co-active brain regions.
On the eve of the March for Science, the TWiV team gathers at ASM Headquarters in Washington, DC with guests Stefano and Susie to talk about the state of science communication.
Hosts: Vincent Racaniello...
This study aimed to investigate whether breast volume measured preoperatively with a Kinect 3D sensor could be used to determine the most appropriate implant size for reconstruction.
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Publication date: Available online 23 April 2017
Source:Journal of Ethnopharmacology
Author(s): Wei Liu, Yudan Zhu, Yongli Wang, Shenglan Qi, Yuwen Wang, Chao Ma, Shuping Li, Bo Jiang, Xuemei Cheng, Zhengtao Wang, Zhenyu Xuan, Changhong Wang
Ethnopharmacological relevanceAerial parts of Peganum harmala Linn (APP) is used as traditional medical herb for treatment of forgetfulness in Uighur medicine in China. But, the active ingredients and underlying mechanisms are unclear.Aim of the studyThe present study was undertaken to investigate the improvement effects of extract and alkaloid fraction from APP on scopolamine-induced cognitive dysfunction and to elucidate their underlying mechanisms of action, and to support its folk use with scientific evidence, and lay a foundation for its further researches.Materials and methodsThe acetylcholinesterase (AChE) inhibitory activities of extract (EXT), alkaloid fraction (ALK) and flavanoid fraction (FLA) from APP were evaluated in normal male C57BL/6 mice. The anti-amnesic effects of EXT and ALK from APP were measured in scopolamine-induced memory deficits mice by the Morris water maze (MWM) tasks. The levels of biomarkers, enzyme activity and protein expression of cholinergic system were determined in brain tissues.ResultsThe AChE activity was significantly decreased and the content of neurotransmitter acetylcholine (ACh) was significantly increased in normal mice cortex and hippocampus by treatment with donepezil at dosage of 8mg/kg, EXT at dosages of 183, 550, 1650 mg/kg and ALK at dosages of 10, 30, 90mg/kg (P < 0.05), and the AChE activity and the content of ACh were not significantly changed in cortex and hippocampus after treatment with FLA at dosages of 10, 30, 90mg/kg (P > 0.05). In the MWM task, scopolamine-induced a decrease in both the swimming time within the target zone and the number of crossings where the platform had been placed were significantly reversed by treatment with EXT at dosages of 550, 1650 mg/kg and ALK at dosages of 30, 90mg/kg (P < 0.05). Moreover, the activity and protein expression of AChE was significantly decreased and the content of neurotransmitter ACh was significantly increased in cerebral cortex of scopolamine-induced mice by treatment with EXT at dosages of 183, 550, 1650 mg/kg and ALK at dosages of 10, 30, 90mg/kg (P < 0.05), compared with scopolamine-treated group.ConclusionsEXT and ALK from APP exert beneficial effect on learning and memory processes in mice with scopolamine-induced memory impairment. APP is an effective traditional folk medicine and the ALK fraction is proved to be the main effective components for the treatment of forgetfulness. The ALK may be valuable source for lead compounds discovery and drug development for treatment of memory impairment such as in Alzheimer's disease.