bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcutaneous spinal cord stimulation of the cervical cord modulates lumbar networks
Authors: Barss Trevor S. , Parhizi Behdad , Mushahwar Vivian K.
Published: November 2019

It has been established that coordinated arm and leg (A&L) cycling facilitates corticospinal drive and modulation of cervico-lumbar connectivity and ultimately improves overground walking in people with incomplete spinal cord injury or stroke. This study examined the effect of noninvasive transcutaneous spinal cord stimulation (tSCS) on the modulation of cervico-lumbar connectivity. Thirteen neurologically intact adults participated in the study. The excitability of the Hoffmann (H) reflex elicited in the soleus muscle was examined under multiple conditions involving either the arms held in a static position or rhythmic arm cycling while tSCS was applied to either the cervical or lumbar cord. As expected, soleus H-reflex amplitude was significantly suppressed by 19.2% during arm cycling (without tSCS) relative to arms static (without tSCS). Interestingly, tSCS of the cervical cord with arms static significantly suppressed the soleus H-reflex (−22.9%), whereas tSCS over the lumbar cord did not suppress the soleus H-reflex (−3.8%). The combination of arm cycling with cervical or lumbar tSCS did not yield additional suppression of the soleus H-reflex beyond that obtained with arm cycling alone or cervical tSCS alone. The results demonstrate that activation of the cervical spinal cord through both rhythmic arm cycling and tonic tSCS significantly modulates the activity of lumbar networks. This highlights the potential for engaging cervical spinal cord networks through tSCS during rehabilitation interventions to enhance cervico-lumbar connectivity. This connectivity is influential in facilitating improvements in walking function after neurological impairment.

NEW & NOTEWORTHY This is the first study to investigate the modulatory effects of transcutaneous spinal cord stimulation (tSCS) on cervico-lumbar connectivity. We report that both rhythmic activation of the cervical spinal cord through arm cycling and tonic activation of the cervical cord through tSCS significantly modulate the activity of lumbar networks. This suggests that engaging cervical spinal cord networks through tSCS during locomotor retraining interventions may not only enhance cervico-lumbar connectivity but also further improve walking capacity.
Binocular 3D otolith-ocular reflexes: responses of normal chinchillas to tilt and translation
Authors: Hageman Kristin N. , Chow Margaret R. , Roberts Dale , Della Santina Charles C.
Published: November 2019

Head rotation, translation, and tilt with respect to a gravitational field elicit reflexive eye movements that partially stabilize images of Earth-fixed objects on the retinas of humans and other vertebrates. Compared with the angular vestibulo-ocular reflex, responses to translation and tilt, collectively called the otolith-ocular reflex (OOR), are less completely characterized, typically smaller, generally disconjugate (different for the 2 eyes) and more complicated in their relationship to the natural stimuli that elicit them. We measured binocular 3-dimensional OOR responses of 6 alert normal chinchillas in darkness during whole body tilts around 16 Earth-horizontal axes and translations along 21 axes in horizontal, coronal, and sagittal planes. Ocular countertilt responses to 40-s whole body tilts about Earth-horizontal axes grew linearly with head tilt amplitude, but responses were disconjugate, with each eye’s response greatest for whole body tilts about axes near the other eye’s resting line of sight. OOR response magnitude during 1-Hz sinusoidal whole body translations along Earth-horizontal axes also grew with stimulus amplitude. Translational OOR responses were similarly disconjugate, with each eye’s response greatest for whole body translations along its resting line of sight. Responses to Earth-horizontal translation were similar to those that would be expected for tilts that would cause a similar peak deviation of the gravitoinertial acceleration (GIA) vector with respect to the head, consistent with the “perceived tilt” model of the OOR. However, that model poorly fit responses to translations along non-Earth-horizontal axes and was insufficient to explain why responses are larger for the eye toward which the GIA vector deviates.

NEW & NOTEWORTHY As the first in a pair of papers on Binocular 3D Otolith-Ocular Reflexes, this paper characterizes binocular 3D eye movements in normal chinchillas during tilts and translations. The eye movement responses were used to create a data set to fully define the normal otolith-ocular reflexes in chinchillas. This data set provides the foundation to use otolith-ocular reflexes to back-project direction and magnitude of eye movement to predict tilt axis as discussed in the companion paper.
The Role of Immune Regulatory Cells in Nontraumatic Osteonecrosis of the Femoral Head: A Retrospective Clinical Study
Authors: Ma Jinhui , Ge Juncheng , Gao Fuqiang , Wang Bailiang , Yue Debo , Sun Wei , Wang Weiguo
Published: November 2019

The immunologic factors have been implicated in the pathogenesis of osteonecrosis. We aimed to investigate the potential role of immune regulatory cells in the development of osteonecrosis of femoral head (ONFH). Sixty-seven patients diagnosed with ONFH and fifty-eight age-, height-, and weight-matched healthy subjects were included in this retrospective study between September 2015 and September 2018. The flow cytometry was used to test the count, percentage, and ratio of T and B lymphocyte subsets in peripheral blood. The T and B lymphocyte levels were compared among different ARCO stages, CJFH types, and etiology groups. The total lymphocyte count, CD3+T cells, Ts cells (CD3+CD8+), B-1 cell count, and B-1 cells (CD5+CD19+) were significantly higher in the patients with ONFH than those in the control subjects. The percentage of T lymphocytes in the patients with ARCO IV stage was significantly smaller than that in the ONFH patients with ARCO II and III stages. The percentage of inhibitory T lymphocytes in patients with CJFH type L3 was significantly smaller than that in the patients with types L1 and L2. In terms of the different ONFH etiologies, the total lymphocyte count and Ts cells (CD3+CD8+) were significantly lower in the ONFH patients induced by excessive alcohol intake than those in the idiopathic ONFH patients. Our results seem to indicate that immune regulatory cells, such as T and B lymphocytes, play an important role in the pathogenesis of ONFH. The development and progression of ONFH may be associated with immune system imbalance.
Regulatory T Cells in Respiratory Health and Diseases
Authors: Singh Rani , Alape Daniel , de Lima Andrés , Ascanio Juan , Majid Adnan , Gangadharan Sidhu P.
Published: November 2019

Respiratory diseases compromise the health of millions of people all over the world and are strongly linked to the immune dysfunction. CD4+FOXP3+ T regulatory cells, also known as Tregs, have a central role maintaining tissue homeostasis during immune responses. Their activity and clinical impact have been widely studied in different clinical conditions including autoimmune diseases, inflammatory conditions, and cancer, amongst others. Tregs express transcription factor forkhead box P3 (FOXP3), which allows regulation of the immune response through anti-inflammatory cytokines such as IL-10 or transforming growth factor beta (TGF-β) and direct cell-to-cell interaction. Maintenance of immune tolerance is achieved via modulation of effector CD4+ T helper 1, 2 or 17 (Th1, Th2, Th17) cells by Tregs. This review highlights the recent progress in the understanding of Tregs in different disorders of the respiratory system.
Antioxidant and Antiulcerogenic Activity of the Dry Extract of Pods of Libidibia ferrea Mart. ex Tul. (Fabaceae)
Authors: Prazeres Lady D. K. T. , Aragão Ticiana P. , Brito Samara A. , Almeida Cynthia L. F. , Silva Amanda D. , de Paula Mirella M. F. , Farias Juliane S. , Vieira Leucio D. , Damasceno Bolívar P. G. L. , Rolim Larissa A. , Veras Bruno O. , Rocha Ismael G. , Silva Neto Jacinto C. , Bittencourt Milena L. F. , Gonçalves Rita de Cássia R. , Kitagawa Rodrigo R. , Wanderley Almir G.
Published: November 2019

Ethnomedicinal studies in the Amazon community and in the Northeast region of Brazil highlight the use of Libidibia ferrea fruits for the treatment of gastric problems. However, there are no data in the literature of this pharmacological activity. Thus, the aim of this paper is to provide a scientific basis for the use of the dry extract of L. ferrea pods (DELfp) for the treatment of peptic ulcers. Phytochemical characterization was performed by HPLC/MS. In vitro antioxidant activity was assessed using DPPH, ABTS, phosphomolybdenum, and superoxide radical scavenging activity. The gastroprotective activity, the ability to stimulate mucus production, the antisecretory activity, and the influence of -SH and NO compounds on the antiulcerogenic activity of DELfp were evaluated. The healing activity was determined by the acetic acid-induced chronic ulcer model. Anti-Helicobacter pylori activity was investigated. HPLC/MS results identified the presence of phenolic compounds, gallic acid and ellagic acid, in DELfp. The extract showed antioxidant activity in vitro. In ulcers induced by absolute ethanol and acidified ethanol, the ED50 values of DELfp were 113 and 185.7 mg/kg, respectively. DELfp (100, 200, and 400 mg/kg) inhibited indomethacin-induced lesions by 66.7, 69.6, and 65.8%, respectively. DELfp (200 mg/kg) reduced gastric secretion and H+ concentration in the gastric contents and showed to be independent of nitric oxide (NO) and dependent on sulfhydryl (-SH) compounds in the protection of the gastric mucosa. In the chronic ulcer model, DELfp reduced the area of the gastric lesion. DELfp also showed anti-H. pylori activity. In conclusion, DELfp showed antioxidant, gastroprotective, healing, and antiulcerogenic activities. The mechanism of these actions seems to be mediated by different pathways and involves the reduction of gastric secretion and H+ concentration, dependence on sulfhydryl compounds, and anti-H. pylori activity. All these actions support the medicinal use of this species in the management of peptic ulcers.
Research and Application of Radial Borehole Fracturing Based on Numerical Simulation
Authors: Li Xiaolong , He Jiayuan
Published: November 2019

The radial borehole fracturing technology has been applied in a certain number of oilfields with good results being achieved. However, the morphology and variation of fracture still require further study. In this paper, the reservoir model based on formation fluid-solid coupling equation is established with the extended finite element method (XFEM) in ABAQUS, and the fracture morphologies in the single-radial borehole, vertical multiradial borehole, and horizontal multiradial borehole are simulated and analyzed with criteria of maximum principal stress and maximum energy release rate as the damage mechanism. Moreover, the accuracy of numerical simulation results is verified with the large-scale true 3D physical simulation experiment. The results show that the induced stress field along the radial borehole during fracturing is the root cause of fracture directional propagation along the radial borehole whose effective guidance distance reaches 40 m. The vertical multiradial borehole can effectively enhance fracture directional propagation and is capable of reducing fracture initiation pressure. In the horizontal multiradial borehole, the major fracture propagating along each radial borehole is formed in the remote-borehole area, and the secondary fracture connecting the neighboring radial boreholes is formed in the near-borehole zone. Coordination of major and secondary fractures can effectively increase the drainage area and reduce the flow resistance in the near-borehole zone. Based on the research on fracture morphology of multiradial borehole fracturing, the scheme of radial borehole arrangement is optimized and verified through numerical simulation of deliverability. The final optimum borehole arrangement scheme is the intersectional angle of 45° between four orthogonal radial boreholes and horizontal maximum principal stress.
Influence of Acquisition Time on MR Image Quality Estimated with Nonparametric Measures Based on Texture Features
Authors: Obuchowicz Rafał , Piórkowski Adam , Urbanik Andrzej , Strzelecki Michał
Published: November 2019

Correlation of parametrized image texture features (ITF) analyses conducted in different regions of interest (ROIs) overcomes limitations and reliably reflects image quality. The aim of this study is to propose a nonparametrical method and classify the quality of a magnetic resonance (MR) image that has undergone controlled degradation by using textural features in the image. Images of 41 patients, 17 women and 24 men, aged between 23 and 56 years were analyzed. T2-weighted sagittal sequences of the lumbar spine, cervical spine, and knee and T2-weighted coronal sequences of the shoulder and wrist were generated. The implementation of parallel imaging with the use of GRAPPA2, GRAPPA3, and GRAPPA4 led to a substantial reduction in the scanning time but also degraded image quality. The number of degraded image textural features was correlated with the scanning time. Longer scan times correlated with markedly higher ITF image persistence in comparison with images computed with reduced scan times. Higher ITF preservation was observed in images of bones in the spine and femur as compared to images of soft tissues, i.e., tendons and muscles. Finally, a nonparametrized image quality assessment based on an analysis of the ITF, computed for different tissues, correlating with the changes in acquisition time of the MR images, was successfully developed. The correlation between acquisition time and the number of reproducible features present in an MR image was found to yield the necessary assumptions to calculate the quality index.
Aloin Preconditioning Attenuates Hepatic Ischemia/Reperfusion Injury via Inhibiting TLR4/MyD88/NF-κB Signal PathwayIn VivoandIn Vitro
Authors: Du Yichao , Qian Baolin , Gao Lin , Tan Peng , Chen Hao , Wang Ankang , Zheng Tianxiang , Pu Shilin , Xia Xianming , Fu Wenguang
Published: November 2019

Background. Aloin exerts considerable protective effects in various disease models, and its effect on hepatic ischemia-reperfusion (HIR) injury remains unknown. This research is aimed at conducting an in-depth investigation of the antioxidant, anti-inflammatory, and antiapoptosis effects of aloin in HIR injury and explain the underlying molecular mechanisms.Methods.In vivo, different concentrations of aloin were intraperitoneally injected 1 h before the establishment of the HIR model in male mice. The hepatic function, pathological status, oxidative stress, and inflammatory and apoptosis markers were measured.In vitro, aloin (AL, C21H22O9) or lipopolysaccharide (LPS) was added to a culture of mouse primary hepatocytes before it underwent hypoxia/reoxygenation (H/R), and the apoptosis in the mouse primary hepatocytes was analyzed.Results. We found that 20 mg/kg was the optimum concentration of aloin for mitigating I/R-induced liver tissue damage, characterized by decreased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Aloin pretreatment substantially suppressed the generation of hepatic malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), and IL-6 and enhanced the hepatic superoxide dismutase (SOD) activities as well as glutathione (GSH) and IL-10 levels in the liver tissue of I/R mice; this indicated that aloin ameliorated I/R-induced liver damage by reducing the oxidative stress and inflammatory response. Moreover, aloin inhibited hepatocyte apoptosis and inflammatory response that was caused by the upregulated expression of Bcl-2, the downregulated expression of cleaved caspase3(C-caspase3), Bax, Toll-like receptor 4 (TLR4), FADD, MyD88, TRAF6, phosphorylated IKKα/β(p-IKKα/β), and phosphorylated nuclear factorκB p65 (p-NF-κB p65).
Functionality Analysis of Spent Coffee Ground Extracts Obtained by the Hydrothermal Method
Authors: Wu Chin-Tung , Agrawal Dinesh Chandra , Huang Wen-Ying , Hsu Hsiu-Cheng , Yang Shang-Jhen , Huang Shu-Ling , Lin Yung-Sheng
Published: November 2019

Coffee is a popular beverage all over the world, but spent coffee grounds (SCGs) constituting almost 75% of original beans are usually considered waste and disposed off. The present study analyzed the functionalities of SCG with a view of its reuse in the cosmetic industry. The SCG extraction was carried out by the hydrothermal method. The resultant extracts were tested for its antioxidant capacity, tyrosinase inhibition, and moisturizing ability. LC–MS/MS results showed two major components in SCG extracts, namely, trigonelline and caffeine. Also, the SCG contained total flavonoid contents of 29 ± 4.5 mg quercetin equivalents (QE)/g SCG and total phenolic contents of 9.44 ± 0.90 mg gallic acid equivalents (GAE)/g SCG. Regarding functionality analysis, SCG extracts exhibited reduction capacity of 8.18 ± 0.39 mg vitamin C equivalent (VCE)/g SCG, DPPH free-radical scavenging activity (IC50) of 3.11 mg SCG/mL, ABTS free-radical scavenging activity (IC50) of 13.61 mg SCG/mL, and tyrosinase inhibition capacity (IC50) of 2.23 mg SCG/mL. Moreover, the volatilization rate of the extract solution (37 mg SCG/mL) reduced by 15.9%. These results demonstrate the utility of recycling of SCG and illustrate its potential application in the development of skin care products.
Neurosurgical Care of Nonpowder Firearm Injuries: A Narrative Review of the Literature
Authors: Wan Yizhou , Griffiths Stewart , Ganau Mario
Published: November 2019

Background. Nonpowder firearms discharge a projectile using compressed gases. Unlike traditional firearms, there is a perception that nonpowder guns do not cause serious injury. However, intracranial injury disproportionally affects children and can cause significant neurological disabilities and mortality. Management of nonpowder firearm injuries has received little attention in the literature and presents unique surgical challenges.Materials and Methods. We conducted a narrative review of the literature of the management of nonpowder firearm injuries with particular emphasis on intracranial injury.Results. Modern nonpowder firearms have muzzle velocities which are capable of penetrating the skin, eyes, and bone. Direct intracranial injury commonly results from entrance of projectile through thinner portions of the skull. Operative intervention is needed to debride and safely explore the trajectory to remove fragments which can easily cause neurovascular injury.Conclusions. Neurosurgeons play a crucial role in managing serious nonpowder firearm injuries. A multidisciplinary team is needed to manage the direct results of penetrating injury and long-term sequalae.
Therapeutic Potential of Human Amniotic Epithelial Cells on Injuries and Disorders in the Central Nervous System
Authors: Xu Huiming , Zhang Jiaofei , Tsang Kam Sze , Yang Hao , Gao Wei-Qiang
Published: November 2019

Despite recent advances in neurosurgery and pharmaceuticals, contemporary treatments are ineffective in restoring lost neurological functions in patients with injuries and disorders of the central nervous system (CNS). Therefore, novel and effective therapies are urgently needed. Recent studies have indicated that stem cells, including embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and mesenchymal stem cells (MSCs), could repair/replace damaged or degenerative neurons and improve functional recovery in both preclinical and clinical trials. However, there are many unanswered questions and unsolved issues regarding stem cell therapy in terms of potency, stability, oncogenicity, immune response, cell sources, and ethics. Currently, human amniotic epithelial cells (hAECs) derived from the amnion exhibit considerable advantages over other stem cells and have drawn much attention from researchers. hAECs are readily available, pose no ethical concerns, and have little risk of tumorigenicity and immunogenicity. Mounting evidence has shown that hAECs can promote neural cell survival and regeneration, repair affected neurons, and reestablish damaged neural connections. It is suggested that hAECs may be the most promising candidate for cell-based therapy of neurological diseases. In this review, we mainly focus on recent advances and potential applications of hAECs for treating various CNS injuries and neurodegenerative disorders. We also discuss current hurdles and challenges regarding hAEC therapies.
Dibromoacetic Acid Induced Hepatotoxicity in Mice through Oxidative Stress and Toll-Like Receptor 4 Signaling Pathway Activation
Authors: Gong Tingting , Jiang Wenbo , Gao Zhijian , Chen Yingying , Gao Shuying
Published: November 2019

Dibromoacetic acid (DBA) is one of haloacetic acids, often as a by-product of disinfection in drinking water. DBA is a multiple-organ carcinogen in rodent animals, but little research on its hepatotoxicity has been conducted and its mechanism has not been elucidated. In this study, we found that DBA could induce obvious hepatotoxcity in Balb/c mice as indicated by histological changes, increasing serum level of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and accumulation of hepatic glycogen, after the mice were administered DBA at doses of 1.25, 5, and 20 mg/kg body weight for 28 days via oral gavage. In mechanism study, DBA induced oxidative stress as evidenced by increasing the level of malondialdehyde (MDA), reactive oxygen species (ROS) in the liver, advanced oxidative protein products (AOPPs) in the serum, and decreasing the level of glutathione (GSH) in the liver. DBA induced inflammation in the liver of the mice which is supported by increasing the production of tumor necrosis factor-α (TNF-α) and the mRNA levels of TNF-α, interleukin-6 (IL-6), interleukin-1β (IL-1β), and nuclear factor κB (NF-κB) in the liver. DBA also upregulated the protein levels of Toll-like receptor (TLR) 4, myeloid differentiation factor 88 (MyD88), tumor necrosis factor receptor-associated factor 6 (TRAF6), inhibitor of nuclear factor κB alpha (IκB-α), nuclear factor κB p65 (NF-κB p65), and the phosphoralation of P38 mitogen-activated protein kinase (P38MAPK) and c-Jun N-terminal kinase (JNK). Conclusion. DBA could induce hepatotoxicity in mice by oral exposure; the mechanism is related to oxidative stress, inflammation, and Toll-like receptor 4 signaling pathway activation.
Effects of Angiotensin-(1-7) and Angiotensin II on Acetylcholine-Induced Vascular Relaxation in Spontaneously Hypertensive Rats
Authors: Zhang Feng , Xu Yu , Pan Yan , Sun Shuo , Chen Aidong , Li Peng , Bao Changlei , Wang Jian , Tang Haiyang , Han Ying
Published: November 2019

Endothelial dysfunction of small arteries occurs in patients with hypertension and in various hypertensive models. Endothelial function is usually evaluated by the degree of acetylcholine- (ACh-) induced vascular relaxation. Our previous study has found that compared to Wistar-Kyoto rats (WKY), ACh-induced vasodilatation was attenuated significantly in the mesenteric artery (MA), coronary artery (CA), and pulmonary artery (PA) of spontaneously hypertensive rats (SHR). This study investigated the influence of angiotensin- (Ang-) (1-7) and Ang II on blood pressure and ACh-induced vascular relaxation, as well as their interactive roles and downstream signal pathways in SHR and WKY. Intravenous injection of Ang II significantly increased, while Ang-(1-7) decreased the mean arterial pressure (MAP) in SHR. Ang-(1-7) improved ACh-induced relaxation in the MA, CA, and PA of SHR, while Ang II further attenuated it, which were inhibited by pretreatment with Mas receptor antagonist A-779 or AT1 receptor antagonist losartan, respectively. Ang-(1-7) decreased the basal arterial tension, and Ang II induced great vasoconstriction in SHR. Pretreatment with Ang-(1-7) inhibited the Ang II-induced pressor response, vasoconstriction, and the effects on ACh-induced relaxation in SHR. AT1 receptor expression was higher, while nitric oxide (NO), cGMP, and protein kinase G (PKG) levels of arteries were lower in SHR than in WKY. Ang II decreased, while Ang-(1-7) increased, the levels of NO, cGMP, and PKG of arteries. In addition, pretreatment with Ang-(1-7) inhibited the Ang II-induced reduction of NO, cGMP, and PKG in SHR. These results indicate that the activation of the Mas receptor by Ang-(1-7) can improve endothelial function and decrease MAP in SHR and inhibit the deteriorative effect of Ang II on endothelial function through the NO-cGMP-PKG pathway.
Interactions between Intestinal Microflora/Probiotics and the Immune System
Authors: Zhang Chen-xing , Wang Hui-yu , Chen Tong-xin
Published: November 2019

The digestive tract is home to millions of microorganisms and is the main and most important part of bacterial colonization. On one hand, the abundant bacterial community in intestinal tissues may pose potential health challenges such as inflammation and sepsis in cases of opportunistic invasion. Thus, the immune system has evolved and adapted to maintain the symbiotic relationship between host and microbiota. On the other hand, the intestinal microflora also exerts an immunoregulatory function to maintain host immune homeostasis, which cannot be neglected. In addition, the interaction of either microbiota or probiotics with immune system in regard to therapeutic applications is an area of great interest, and novel therapeutic strategies remain to be investigated. The review will elucidate interactions between intestinal microflora/probiotics and the immune system as well as novel therapeutic strategies.
Algebraic Degree Estimation of ACORN v3 Using Numeric Mapping
Authors: Ding Lin , Wang Lei , Gu Dawu , Jin Chenhui , Guan Jie
Published: November 2019

ACORN v3 is a lightweight authenticated encryption cipher, which was selected as one of the seven finalists of CAESAR competition in March 2018. It is intended for lightweight applications (resource-constrained environments). By using the technique numeric mapping proposed at CRYPTO 2017, an efficient algorithm for algebraic degree estimation of ACORN v3 is proposed. As a result, new distinguishing attacks on 647, 649, 670, 704, and 721 initialization rounds of ACORN v3 are obtained, respectively. So far, as we know, all of our distinguishing attacks on ACORN v3 are the best. The effectiveness and accuracy of our algorithm is confirmed by the experimental results.
Sucrose Promotes Strawberry Fruit Ripening and Affects Ripening-Related Processes
Authors: Luo Ya , Lin Yuanxiu , Mo Fan , Ge Cong , Jiang Leiyu , Zhang Yong , Chen Qing , Sun Bo , Wang Yan , Wang Xiaorong , Tang Haoru
Published: November 2019

Strawberry is a typical nonclimacteric fruit, whose ripening mechanism needs to be further investigated. Sucrose has been recently proved as a signal molecule, participating in strawberry fruit ripening and related processes. While in the effects of sucrose application timing and concentration on ripening, fruit qualities remain unclear, as well as the transcriptome-wide details about the effects of sucrose on the gene expression involved in ripening-related processes. In this study, strawberry fruits at the degreening (DG), white (W), and initial-red (IR) stages were treated with different concentration of sucrose. The results showed that anthocyanin was increased while total polyphenol concentration (TPC) and total flavonoid concentration (TFC) were decreased during fruit development after sucrose treatment. Interestingly, It was showed that 100 mM sucrose application at the DG stage had the most obvious effects on fruit ripening; it made all the fruits turn into full-red (FR) around 4 days (d) earlier than the control, while it did not affect fruit quality traits and most bioactive compounds in the FR fruits. Subsequently, RNA sequencing (RNAseq) of the fruits collected at 8 days after 100 mM sucrose treatment was carried out. It was suggested that 993 genes were differentially expressed comparing with the control. Transcriptome-based expression analysis revealed that sucrose induced the expression of genes involved in the AsA and anthocyanin biosynthesis, while largely suppressed the expression of genes in TCA. The results obtained in this study provided more expression profiles of ripening-related genes under the treatment of sucrose, which will contribute to a better understanding for the mechanism underlying sucrose-induced fruit ripening.
Gastrodin Ameliorates Acute Rejection via IRE1α/TRAF2/NF-κB in Rats Receiving Liver Allografts
Authors: Yuan Fangchao , Xu Xuesong , Wu Yakun , Duan Shigang , Wu Hao
Published: November 2019

Background. Liver transplantation (LT) is currently an effective treatment for end-stage liver disease, but the occurrence of acute rejection (AR) is still the main problem to be solved. The present study aimed to evaluate the effect of gastrodin (GAS) on LT. Methods. Rat transplant models were established and divided into SHAM, LT, GAS-L (50 mg/kg GAS), and GAS-H (100 mg/kg GAS) groups. The liver function, inflammatory factors, liver histopathology, survival of rats, number of M2-type macrophages, liver cell apoptosis, and pathway proteins were assayed at 7 days and 14 days after the operations. Results. With increasing GAS concentrations, liver function, expression of proinflammatory factors in the liver, and expression of M2-type molecules in macrophages were significantly improved, and the survival time of rats was significantly prolonged (P<0.05). All rats treated with low or high doses of GAS were judged to have nondeterministic acute rejection. Flow cytometry showed that liver cell apoptosis was decreased significantly in the GAS-L and GAS-H groups after GAS administration compared with apoptosis and differentiation in the LT group (P<0.05). Expression levels of Caspase-3, Bad, and Bax proteins were decreased, and the expression of the antiapoptotic protein Bcl-2 was increased in the GAS-L and GAS-H groups (P<0.05). Mechanistically, the ERS-related IRE1α/TRAF2/NF-κB pathway was suppressed by GAS, and GAS acted mainly on intrahepatic macrophages to affect AR and reduce ROS production (P<0.05). Conclusion. GAS ameliorated AR by inhibiting the IRE1α/TRAF2/NF-κB pathway in LT.
Human Leukocyte Antigen (HLA) and Islet Autoantibodies Are Tools to Characterize Type 1 Diabetes in Arab Countries: Emphasis on Kuwait
Authors: Jahromi Mohamed , Al-Ozairi Ebaa
Published: November 2019

The incidence rate of type 1 diabetes in Kuwait had been increasing exponentially and has doubled in children≤14 years old within almost two decades. Therefore, there is a dire need for a careful systematic familial cohort study. Several immunogenetic factors affect the pathogenesis of the disease. The human leukocyte antigen (HLA) accounts for the major genetic susceptibility to the disease. The triggering agents initiate disease onset by type 1 destruction of pancreatic β-cells. Both HLA and anti-islet antibodies can be used to characterize, predict susceptibility to the disease, innovate, or delay the β-cell destruction. Evidence from prospective longitudinal studies suggested that the underlying disease process represents a continuum that begins before the symptoms are clinically evident. Autoimmunity of the functional pancreatic β-cells results in symptomatic type 1 diabetes and lifelong insulin dependence. The autoantibodies against glutamic acid decarboxylase (GADA), insulinoma antigen-2 (IA-2A), insulin (IAA), and zinc transporter-8 (ZnT-8A) comprise the most reliable biomarkers for type 1 diabetes in both children and adults. Although Kuwait is the second among the top 10 countries with a high incidence rate of type 1 diabetes, there have been no proper diagnostic and prediction tools as per the World Health Organization. The Kuwaiti Type 1 Diabetes Study (KADS) was initiated to understand the disease pathogenesis as well as the HLA and anti-islet autoantibody profile of type 1 diabetes in Kuwait. Understanding the disease sequela in a homogenous gene pool and highly consanguineous population of Kuwaitis could help solve the challenges and pathogenesis, as well as hasten the prevention, of type 1 diabetes.
Cost-Effectiveness of Personalized Screening for Colorectal Cancer Based on Polygenic Risk and Family History
Authors: Cenin Dayna R. , Naber Steffie K. , de Weerdt Anne C. , Jenkins Mark A. , Preen David B. , Ee Hooi C. , O'Leary Peter C. , Lansdorp-Vogelaar Iris
Published: November 2019

Background:

There is growing evidence for personalizing colorectal cancer screening based on risk factors. We compared the cost-effectiveness of personalized colorectal cancer screening based on polygenic risk and family history to uniform screening.

Methods:

Using the MISCAN-Colon model, we simulated a cohort of 100 million 40-year-olds, offering them uniform or personalized screening. Individuals were categorized based on polygenic risk and family history of colorectal cancer. We varied screening strategies by start age, interval and test and estimated costs, and quality-adjusted life years (QALY). In our analysis, we (i) assessed the cost-effectiveness of uniform screening; (ii) developed personalized screening scenarios based on optimal screening strategies by risk group; and (iii) compared the cost-effectiveness of both.

Results:

At a willingness-to-pay threshold of $50,000/QALY, the optimal uniform screening scenario was annual fecal immunochemical testing (FIT) from ages 50 to 74 years, whereas for personalized screening the optimal screening scenario consisted of annual and biennial FIT screening except for those at highest risk who were offered 5-yearly colonoscopy from age 50 years. Although these scenarios gained the same number of QALYs (17,887), personalized screening was not cost-effective, costing an additional $428,953 due to costs associated with determining risk (assumed to be $240 per person). Personalized screening was cost-effective when these costs were less than ∼$48.

Conclusions:

Uniform colorectal cancer screening currently appears more cost-effective than personalized screening based on polygenic risk and family history. However, cost-effectiveness is highly dependent on the cost of determining risk.

Impact:

Personalized screening could become increasingly viable as costs for determining risk decrease.
Genetic Association of Plasma Homocysteine Levels with Gastric Cancer Risk: A Two-Sample Mendelian Randomization Study
Authors: Wang Tianpei , Ren Chuanli , Ni Jing , Ding Hui , Qi Qi , Yan Caiwang , Deng Bin , Dai Juncheng , Li Gang , Ding Yanbing , Jin Guangfu
Published: November 2019

Background:

The association of plasma homocysteine level (PHL) with gastric cancer risk was reported in observational studies. However, the causality is challenging due to confounding factors and the lack of evidence from well-designed cohort studies. Herein, we performed a two-sample Mendelian randomization (MR) analysis to investigate whether PHL is causally related to gastric cancer risk.

Methods:

We performed the MR analysis based on the results from genome-wide association studies consisting of 2,631 patients with gastric cancer and 4,373 controls. An externally weighted genetic risk score (wGRS) was constructed with 15 SNPs with well-established associations with PHL. We utilized logistic regression model to estimate associations of PHL-related SNPs and wGRS with gastric cancer risk in total population and in strata by sex, age, and study site, in addition to a series of sensitivity analyses.

Results:

High genetically predicted PHL was associated with an increased gastric cancer risk (per SD increase in the wGRS: OR = 1.07; 95% confidence interval, 1.01–1.12; P = 0.011), which was consistent in sensitivity analyses. Subgroup analyses provided evidence of a stronger association with gastric cancer risk in women than in men. MR-Egger and weighted median regression suggested that potentially unknown pleiotropic effects were not biasing the association between PHL and gastric cancer risk.

Conclusions:

These results revealed that genetically predicted high PHL was associated with an increased gastric cancer risk, suggesting that high PHL may have a causal role in the etiology of gastric cancer.

Impact:

These findings provide causal inference for PHL on gastric cancer risk, suggesting a causal role of high PHL in the etiology of gastric cancer.
Using Digital Pathology to Understand Epithelial Characteristics of Benign Breast Disease among Women Undergoing Diagnostic Image-Guided Breast Biopsy
Authors: Mullooly Maeve , Puvanesarajah Samantha , Fan Shaoqi , Pfeiffer Ruth M. , Olsson Linnea T. , Hada Manila , Kirk Erin L. , Vacek Pamela M. , Weaver Donald L. , Shepherd John , Mahmoudzadeh Amir , Wang Jeff , Malkov Serghei , Johnson Jason M. , Hewitt Stephen M. , Herschorn Sally D. , Sherman Mark E. , Troester Melissa A. , Gierach Gretchen L.
Published: November 2019

Delayed terminal duct lobular unit (TDLU) involution is associated with elevated mammographic breast density (MD). Both are independent breast cancer risk factors among women with benign breast disease (BBD). Prior digital analyses of normal breast tissues revealed that epithelial nuclear density (END) and TDLU involution are inversely correlated. Accordingly, we examined associations of END, TDLU involution, and MD in BBD clinical biopsies. This study included digitized images of 262 representative image-guided hematoxylin and eosin–stained biopsies from 224 women diagnosed with BBD, enrolled within the cross-sectional BREAST-Stamp project that were visually assessed for TDLU involution (TDLU count/100 mm2, median TDLU span and median acini count per TDLU). A digital algorithm estimated nuclei count per unit epithelial area, or END. Single X-ray absorptiometry of prebiopsy ipsilateral craniocaudal digital mammograms measured global and localized MD surrounding the biopsy region. Adjusted ordinal logistic regression models assessed relationships between tertiles of TDLU and END measures. Analysis of covariance examined mean differences in MD across END tertiles. TDLU measures were positively associated with increasing END tertiles [TDLU count/100 mm2, ORT3vsT1: 3.42, 95% confidence interval (CI), 1.87–6.28; acini count/TDLUT3vsT1, OR: 2.40, 95% CI, 1.39–4.15]. END was significantly associated with localized, but not, global MD. Relationships were most apparent among patients with nonproliferative BBD. These findings suggest that quantitative END reflects different but complementary information to the histologic information captured by visual TDLU and radiologic MD measures and merits continued evaluation in assessing cellularity of breast parenchyma to understand the etiology of BBD.
Methyl Donor Deficiency Blocks Colorectal Cancer Development by Affecting Key Metabolic Pathways
Authors: Hanley Matthew P. , Aladelokun Oladimeji , Kadaveru Krishna , Rosenberg Daniel W.
Published: November 2019

Our understanding of the role of folate one-carbon metabolism in colon carcinogenesis remains incomplete. Previous studies indicate that a methyl donor–deficient (MDD) diet lacking folic acid, choline, methionine, and vitamin B12 is associated with long-lasting changes to the intestinal epithelium and sustained tumor protection in Apc-mutant mice. However, the metabolic pathways by which the MDD diet affects these changes are unknown. Colon samples harvested from ApcΔ14/+ mice fed the MDD diet for 18 weeks were profiled using a GC-MS and LC-MS/MS metabolomics platform. Random forest and pathway analyses were used to identify altered metabolic pathways, and associated gene expression changes were analyzed by RT-PCR. Approximately 100 metabolites affected by the MDD diet were identified. As expected, metabolites within the methionine cycle, including methionine (−2.9-fold, P < 0.001) and betaine (−3.3-fold, P < 0.001), were reduced. Elevated homocysteine (110-fold, P < 0.001) was associated with increased flux through the transsulfuration pathway. Unexpectedly, levels of deoxycholic acid (−4.5-fold, P < 0.05) and several other secondary bile acids were reduced. There were also unexpected reductions in the levels of carnitine (−2.0-fold, P < 0.01) and a panel of acylcarnitines involved in fatty acid β-oxidation. Finally, metabolites involved in redox balance, including ascorbate and hypotaurine, were found to be persistently elevated. These findings provide clues to the molecular changes underlying MDD-mediated tumor protection and identify regulatable metabolic pathways that may provide new targets for colon cancer prevention and treatment.

Implications:

Metabolomic profiling reveals molecular changes underlying MDD-induced tumor protection and may provide new targets for colorectal cancer prevention and treatment.
Digital Papillary Adenocarcinoma, a Rare Malignant Tumor
Authors: Vale Cláudia , Carvalho André , Roseiro Tiago , Antunes João , Tellechea Óscar , Oliveira Vasco
Published: November 2019

We present a case report of a digital papillary adenocarcinoma (DPA) on the left thumb with slow growth that was completely excised, without recurrence or metastasis during 24-month follow-up. DPA is a rare malignant tumor often located on the digits of the hand. Due to its slow growth and a non-specific appearance, the diagnosis is often missed or delayed. Treatment should be surgical with clear resection of the margins due to high risk of recurrence and/or metastasis.
Mobilidade funcional, força, medo de cair, estilo e qualidade de vida em idosos praticantes de caminhada
Authors: Silva Clévia Da , Oliveira Natália Cristina de , Alfieri Fábio Marcon
Published: November 2019

O processo de envelhecimento envolve modificações no desempenho locomotor que podem predispor os idosos a quedas e alterações na qualidade de vida. Objetivo: Comparar o medo de cair, mobilidade funcional, força de membros inferiores, estilo e qualidade de vida em idosos sedentários e praticantes caminhada. Método: Trata-se de estudo transversal observacional do qual participaram 51 idosos, 25 praticantes de caminhada (GCam) e 26 sedentários (GSed), submetidos à avaliação de mobilidade funcional (Timed Up and Go - TUG), da força de membros inferiores (teste senta-levanta), medo de cair (Escala Internacional de Eficácia de Quedas - FES-I), estilo de vida (questionário FANTASTICO) e Qualidade de vida (SF-36). Resultados: Não houve diferença entre os grupos em relação às médias de idade, distribuição de gênero e índice de massa corporal. Os participantes do GCam apresentaram mobilidade funcional significantemente melhor (9,45±2,68 vs. 14,97±6,55 segundos; p=0,001) que os do GSed, e menos medo de cair (23,16±5,33 vs. 29,04±10,22; p=0,01). O estilo de vida também foi superior entre os praticantes de caminhada (79,84±5,52 vs. 67,19±10,35; (p=0,0001). Em relação à qualidade de vida, o GCam apresentou escores maiores nos domínios capacidade funcional (p=0,013), limitações por aspecto físico (p=0,17) e limitações por aspectos emocionais (p=0,05). Já no domínio dor, o GCam apresentou pior resultado (p=0,05) em relação ao GSed. Conclusão: Idosos praticantes regulares de caminhada possuem melhor resultados em relação à mobilidade funcional, habilidade de levantar e sentar, menos medo de cair, melhor estilo de vida e alguns domínios da qualidade de vida do que idosos sedentários.
Síndrome de Burnout em fisioterapeutas de um hospital público de alta complexidade da cidade do Recife, Pernambuco
Authors: Santos Ericky Rafael , Neri Luana Valeriano , Wanderley Elaine Lima Silva
Published: November 2019

Por serem expostos às inadequadas condições de trabalho, os Fisioterapeutas podem desenvolver a síndrome de Burnout (SB), que é uma resposta ao estresse crônico associado ao ambiente ocupacional. Objetivo: Investigar a frequência da SB em Fisioterapeutas de um hospital público, verificando associações com variáveis demográficas e laborais. Métodos: Este estudo foi desenvolvido no Hospital da Restauração Governador Paulo Guerra, em 2015. Foram incluídos Fisioterapeutas atuantes no hospital e excluídos aqueles com história de depressão ou outros transtornos emocionais. O questionário autoaplicável Maslach Burnout Inventory foi utilizado para investigar a SB. Estatística descritiva foi utilizada para caracterizar a amostra e determinar a frequência da SB, a regressão multivariada foi utilizada para verificar relações entre a SB e as variáveis demográficas e laborais (p<0,05). Resultados: Participaram deste estudo 48 fisioterapeutas. A maioria atuava nas unidades de terapia intensiva (56,3% (N=27)). A presença da SB foi identificada em 54,2% (N=26) dos participantes. Foram observadas correlações entre o número de atendimentos diários e a exaustão emocional (r= 0,41) e com a realização pessoal (r= -0,30), e da idade com a despersonalização (r= -0,11). Conclusão: A SB foi verificada em mais da metade dos Fisioterapeutas. Correlações positivas foram observadas entre o número de atendimentos diários e a exaustão emocional e correlação negativa entre a idade com despersonalização e número de atendimentos diários com a realização pessoal.
Protocolo de assistência do serviço de condicionamento físico para indivíduos com doenças neuromusculares e musculoesqueléticas
Authors: Cardoso Cristiane Vieira , Mota Cristiane Gonçalves , Sampaio Isabel Cristina da Silva Prado , Sabbag Livia Maria dos Santos
Published: November 2019

O condicionamento físico supervisionado por profissionais de Educação Física inserido em um programa de reabilitação para pacientes com distúrbios neuromusculares e musculoesqueléticos visa o aumento da força muscular, melhora da coordenação motora, equilíbrio dinâmico, capacidade aeróbia, capacidade funcional e da aptidão física voltada à saúde. Trata-se de importante intervenção para prevenir e atenuar a sinergia entre a perda de função física e a exacerbação de várias comorbidades que comprometem a independência funcional, modificar fatores de risco, aumentar a qualidade de vida e longevidade com redução da mortalidade. O objetivo desse artigo é apresentar o protocolo de assistência do Serviço de Condicionamento Físico do Instituto de Medicina Física e Reabilitação do Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo (IMREA-HCFMUSP), elaborado para que a intervenção de exercícios físicos seja adequada, respeitando o perfil e limitações físicas desses pacientes, bem como na observação de seus marcadores clínicos.