Genome-wide analysis of MATE transporters and molecular characterization of aluminum resistance in Populus.

Abstract: Ionic aluminum (Al) in acidic soils, comprising approximately 50% of arable land globally, is highly toxic to most plant species. Populus grow naturally in acidic soils and tolerate high concentrations of Al. Multidrug and toxic compound extrusion (MATE) family genes in plants are involved in responses to Al tolerance. To date, however, the functional roles of the MATE genes in Populus remain unclear. In the present study, 71 putative MATE transporters were predicted in the genome of Populus trichocarpa. The chromosome distribution, phylogenetic relationships, and expression level analysis revealed that four candidate MATE genes belonging to subgroup IIIc might contribute to high Al tolerance in poplar. Further, the expression levels of two subgroup IIIc members, PtrMATE1 and PtrMATE2, were induced by Al stress. Transient expression in onion epidermal cells showed that PtrMATE1 was localized to the plasma membrane. Overexpression of PtrMATE1 increased Al-induced secretion of citrate from the root apex of transgenic plants. Al-induced inhibition of root growths were alleviated in both PtrMATE1 overexpression lines in Populus and in Arabidopsis compared with wild-type plants. In addition, PtrMATE1 expression was induced at 12 h after exposure to Al stress whereas PtrMATE2 expression was induced at 24 h, indicating that these proteins coordinately function in response to Al stress in poplar. Taken together, these results provide important insights into the molecular mechanisms involved in Al tolerance in poplar.

Li|Nannan|N| Meng|Hongjun|H| Xing|Haitao|H| Liang|Lan|L| Zhao|Xin|X| Luo|Keming|K|

D027701:Organic Cation Transport Proteins

MATE transporter
Populus
root apex
Aluminum stress
citrate exudation


The behavioral and endocrinological development of stress response in dogs.

Abstract: Endocrinological stress response has been shown to be absent in a specific period of the early life of rodents; this is named the stress-hyporesponsive period (SHRP). The SHRP is a significant period for the appropriate development of infants. In this study, the presence of SHRP in dogs was identified by conducting a 5-min separation test in 142 Labrador retriever puppies in their early socialization period and measuring the changes in urinary cortisol levels. An increase in cortisol after separation was found after 5 weeks of age, suggesting that the SHRP persists until 4 weeks of age in dogs. The distress vocalization during separation changed and the lactating behavior decreased rapidly around 5 weeks of age, suggesting that the endocrinological and emotional aspects of development change at approximately 5 weeks of age and maternal inhibition of cortisol might occur in dogs as well as rodents.

Nagasawa|Miho|M| Shibata|Yoh|Y| Yonezawa|Akiko|A| Morita|Tomoko|T| Kanai|Masanori|M| Mogi|Kazutaka|K| Kikusui|Takefumi|T|

dog
stress-hyporesponsive period
cortisol
vocalization
maternal behavior


An evaluation on different origins of natural organic matters using various anodes by electrocoagulation.

Abstract: In this investigation, natural organic matters (NOM) of different origins (commercial, terrestrial and natural water) were treated by electrocoagulation (EC) process using aluminum, iron and hybrid electrodes. Electrode type effect on removal efficiency was observed for each NOM (commercial, terrestrial, and natural). The results were presented as dissolved organic carbon (DOC) (mg L(-1)) and UV/VIS absorbance (cm(-1)). The specific UV absorbance (SUVA) was determined before and after treatment of water. The lowest effluent concentration was obtained as 5.05 mg L(-1) with hybrid electrode for natural NOM source at its original pH 7.3. In addition, among the metal types, the best UV-abs-254 removal efficiency was obtained as 92.4% with 0.0312 cm(-1) by hybrid electrode at the end of the process. The color removal efficiency of water occurred successfully by Al and hybrid electrodes. Aquatic NOM source was the most resistant to EC treatment with DOC reduction of 71.1%, 59.8%, and 68.6% for Al, Fe and hybrid electrodes, respectively. Zeta potential and floc size of colloids were observed during the process for the determination of destabilization level of natural organic matters in EC process. Fast coagulation or flocculation and incipient instability were formed during electrolysis time for Al and Fe electrode, respectively. SUVA value was reduced to below 2 for three NOM sources studied. The EC process was shown to be a viable for different NOM sources with various metals.

Ulu|Feride|F| Barışçı|Sibel|S| Kobya|Mehmet|M| Sillanpää|Mika|M|

NOM
Electrocoagulation (EC)
Zeta potential
Floc size


Virtual Learning Simulations in High School: Effects on Cognitive and Non-cognitive Outcomes and Implications on the Development of STEM Academic and Career Choice.

Abstract: The present study compared the value of using a virtual learning simulation compared to traditional lessons on the topic of evolution, and investigated if the virtual learning simulation could serve as a catalyst for STEM academic and career development, based on social cognitive career theory. The investigation was conducted using a crossover repeated measures design based on a sample of 128 high school biology/biotech students. The results showed that the virtual learning simulation increased knowledge of evolution significantly, compared to the traditional lesson. No significant differences between the simulation and lesson were found in their ability to increase the non-cognitive measures. Both interventions increased self-efficacy significantly, and none of them had a significant effect on motivation. In addition, the results showed that the simulation increased interest in biology related tasks, but not outcome expectations. The findings suggest that virtual learning simulations are at least as efficient in enhancing learning and self-efficacy as traditional lessons, and high schools can thus use them as supplementary educational methods. In addition, the findings indicate that virtual learning simulations may be a useful tool in enhancing student's interest in and goals toward STEM related careers.

virtual learning simulations
STEM
career development
social cognitive career theory
education
e-learning


Methyl-Substituted α-Cyclodextrin as Affinity Material for Storage, Separation, and Detection of Trichlorofluoromethane.

Abstract: The severely ozone-depleting trichlorofluoromethane is still appearing in several recycling processes or industrial applications. A simple and selective supramolecular complex formation of per-methylated α-cyclodextrin (1) with the highly volatile trichlorofluoromethane (2) is reported. This interaction moreover leads to thermally stable crystals. Per-methylated α-cyclodextrin is successfully exploited as a reversible and selective adsorption material for liquid and airborne trichlorofluoromethane as well as an affinity material for the chemical sensing and detection of this particular volatile organic component.

trichlorofluoromethane
CFC‐11
cyclodextrin
optical sensors
supramolecular chemistry


Management of Myocarditis in Myositis: Diagnosis and Treatment.

Abstract:
PURPOSE OF REVIEW
To provide a summary of the current knowledge on myocarditis in idiopathic inflammatory myopathies (IIMs).

RECENT FINDINGS
There is increasing epidemiological knowledge about heart involvement generally and myocarditis specifically in IIMs. Cardiac magnetic resonance (CMR) plays an important role in this regard. Myocarditis occupies an important place in the spectrum of pathologies that involve the myocardium in patients with IIMs. Nevertheless, its full impact still remains to be elucidated. A larger cooperation between rheumatologists and cardiologists in the clinical, as well as in the research field, is necessary to expand our knowledge in the area.

Myocarditis
Idiopathic inflammatory myopathies
Cardiac magnetic resonance
Echocardiography


Exposure to prenatal infection and risk of schizophrenia.

Abstract: We provide a brief review of findings supporting a role for prenatal infection in the etiology of schizophrenia. Our group and others have conducted birth cohort studies to address whether in utero exposure to infectious agents, prospectively documented by biomarker assays of archived maternal sera, and by detailed obstetric records, confer an increased risk of schizophrenia in adult offspring. Prenatal exposure to influenza, elevated toxoplasma antibody, rubella, genital-reproductive infections, and other infections have been associated with an increased risk of schizophrenia among offspring. Animal models have supported these epidemiologic findings by revealing that maternal immune activation causes phenotypes analogous to those found in patients with schizophrenia. Given that exposure to microbial agents are preventable or treatable, they suggest that interventions to diminish the incidence of infection during pregnancy have the potential to prevent an appreciable proportion of schizophrenia cases. Given the clear genetic component to schizophrenia, future studies should include investigations of interactions between prenatal infection and susceptibility genes in the pathogenesis of schizophrenia.

infection
schizophrenia
birth cohort
influenza
rubella
epidemiology
toxoplasmosis


Derivation of male germ cells from induced pluripotent stem cells by inducers: A review.

Abstract: Induced pluripotent stem cells (iPSCs) refer to stem cells that are artificially produced using a new technology known as cellular reprogramming, which can use gene transduction in somatic cells. There are numerous potential applications for iPSCs in the field of stem cell biology becauase they are able to give rise to several different cell features of lineages such as three-germ layers. Primordial germ cells, generated via in vitro differentiation of iPSCs, have been demonstrated to produce functional gametes. Therefore, in this review we discussed past and recent advances in the in vitro differentiation of germ cells using pluripotent stem cells with an emphasis on iPSCs. Although this domain of research is still in its infancy, exploring development mechanisms of germ cells is promising, especially in humans, to promote future reproductive and developmental engineering technologies. While few studies have evaluated the ability and efficiency of iPSCs to differentiate toward male germ cells in vitro by different inducers, the given effect was investigated in this review.

Amini Mahabadi|Javad|J|
Sabzalipoor|Hamed|H|
Kehtari|Mousa|M|
Enderami|Seyed Ehsan|SE|
Soleimani|Masoud|M|
Nikzad|Hossein|H|

germ cells
induced pluripotent stem cells
inducers
differentiation


Clinical Predictors for Lack of Favorable Vascular Response to Statin Therapy in Patients With Coronary Artery Disease: A Serial Optical Coherence Tomography Study.

Abstract:
BACKGROUND
Previous studies have demonstrated that statin therapy improves cardiac outcomes, probably by stabilizing thin-cap fibroatheroma in patients with coronary artery disease. However, major adverse cardiac events still occur in some patients, despite statin therapy. The aim of this study is to identify clinical predictors for the lack of a favorable vascular response to statin therapy in patients with coronary artery disease.

METHODS AND RESULTS
A total of 140 nonculprit plaques from 84 patients with coronary artery disease who were treated with a statin and had serial optical coherence tomography imaging (median interval, 6.3 months) were included. Thin-cap area (fibrous cap thickness, <200 μm) was measured using a novel 3-dimensional computer-aided algorithm. Overall, the thin-cap area significantly decreased from baseline (median, 2.852 mm2; 25th-75th percentile, 1.023-6.157 mm2) to follow-up (median, 1.210 mm2; 25th-75th percentile, 0.250-3.192 mm2; P<0.001), and low-density lipoprotein cholesterol significantly decreased from baseline (mean±SD, 92.9±30.1 mg/dL) to follow-up (mean±SD, 76.3±23.3 mg/dL; P<0.001). The general linear model with multiple predictor variables revealed that the thin-cap area was significantly higher in patients with chronic kidney disease than in those without it (regression coefficient b, 1.691 mm2; 95% confidence interval, 0.350-3.033 mm2; P=0.013) and lower in patients with acute coronary syndrome (regression coefficient b, -1.535 mm2; 95% confidence interval, -2.561 to -0.509 mm2; P=0.003).

CONCLUSIONS
Chronic kidney disease is an independent predictor for the lack of a favorable vascular response to statin therapy, whereas acute coronary syndrome is an independent predictor for favorable vascular response to statin therapy. These findings should be further warranted in future prospective studies.

CLINICAL TRIAL REGISTRATION
URL: http://www.clinicaltrials.gov. Unique identifier: NCT01110538.

Minami|Yoshiyasu|Y|
Wang|Zhao|Z|
Aguirre|Aaron D|AD|
Ong|Daniel S|DS|
Kim|Chong-Jin|CJ|
Uemura|Shiro|S|
Soeda|Tsunenari|T|
Lee|Hang|H|
Fujimoto|James|J|
Jang|Ik-Kyung|IK|

statin therapy
coronary artery disease
optical coherence tomography
fibrous cap
atherosclerosis


Postablation assessment using follow-up registration of CT images before and after radiofrequency ablation (RFA): prospective evaluation of midterm therapeutic results of RFA for hepatocellular carcinoma.

Abstract:
OBJECTIVE
The purpose of this study was to prospectively evaluate the diagnostic impact of prototypic software that allows registration of CT images before and after radiofrequency ablation (RFA) for safety margin assessment, as well as to determine the therapeutic impact of this software on local tumor progression in comparison with the conventional method of side-by-side CT comparison.

SUBJECTS AND METHODS
One-hundred fifty patients with a single hepatocellular carcinoma (HCC) referred for RFA were enrolled. CT scans were obtained before and after RFA, and all CT images were analyzed with and without the use of nonrigid registration software. Thereafter, local tumor progression in the study group (n = 150) was compared with that in a matched control group (n = 90) in which side-by-side comparison of CT images before and after RFA was used for safety margin assessment.

RESULTS
RFA using registration software-assisted diagnoses to decide whether additional RFA was necessary resulted in a 10.67% local tumor progression rate 42 months after the procedure, which was significantly better than that in the matched control group (23.33%) (p = 0.01). After registration software was used, 15.33% (23/150) of patients had conflicting assessments on the safety margin and the necessity for additional RFAs compared with the initial visual comparison of the CT scans.

CONCLUSION
The addition of follow-up registration of CT images before and after RFA resulted in significantly improved assessment of safety margins, simplifying the decision of whether to perform additional treatments and reducing local tumor progression of HCCs after RFA.

Shin|Sooyoung|S|
Lee|Jeong Min|JM|
Kim|Kyung Won|KW|
Joo|Ijin|I|
Han|Joon Koo|JK|
Choi|Byung Ihn|BI|
Klotz|Ernst|E|

D011857:Radiographic Image Interpretation, Computer-Assisted

registration
CT
radiofrequency ablation
ablative margin
liver


Expression of AE1/p16 promoted degradation of AE2 in gastric cancer cells.

Abstract:
BACKGROUND
Human anion exchanger 1 and 2 (AE1 and AE2) mediate the exchange of Cl(-)/HCO3 (-) across the plasma membrane and regulate intracellular pH (pHi). AE1 is specifically expressed on the surface of erythrocytes, while AE2 is widely expressed in most tissues, and is particularly abundant in parietal cells. Previous studies showed that an interaction between AE1 and p16 is a key event in gastric cancer (GC) progression, but the importance of AE2 in GC is unclear.

METHODS
The relationship among AE1, AE2 and p16 in GC cells was characterized by molecular and cellular experiments. AE2 expression and pHi were measured after knockdown or forced expression of AE1 or p16 in GC cells. The effect of AE2 on GC growth and the correlation of AE2 expression with differentiation and prognosis of GC were also evaluated. The effect of gastrin on AE2 expression and GC growth was investigated in cellular experiments and mouse xenograft models.

RESULTS
p16 binds to both AE1 and AE2 simultaneously. AE1 or p16 silencing elevated AE2 expression on the plasma membrane where it plays a role in pHi regulation and GC suppression. AE2 expression was decreased in GC tissue, and these decreased levels were correlated with poor differentiation and prognosis of GC. The low AE2 protein levels are due to rapid ubiquitin-mediated degradation that was facilitated in the presence of p16. Gastrin inhibited the growth of GC cells at least partially through up-regulation of AE2 expression.

CONCLUSION
AE1/p16 expression promoted AE2 degradation in GC cells. Gastrin is a potential candidate drug for targeted therapies for AE1- and p16-positive GC.

Wang|Ting|T| Fei|Hong-Jun|HJ| Yang|Ye|Y| Jiang|Xiao-Shu|XS| Yan|Min|M| Zeng|Zhi|Z| Wu|Jun|J| Song|Ling-Jun|LJ| Tian|Hua|H| Fu|Guo-Hui|GH|

D001457:Anion Exchange Protein 1, Erythrocyte

D019941:Cyclin-Dependent Kinase Inhibitor p16

D023041:Xenograft Model Antitumor Assays


All-cause mortality and suicide within 8 days after emergency department discharge.

Abstract:
AIM
The aim of the study was to evaluate the association of death within 8-30 days after discharge home from the emergency department with a non-causative diagnosis in a prospective cohort study.

METHODS
The 227,097 visits to the emergency department were filed by personal identification number and included information on gender, age, admission, discharge, and diagnosis. The visits were classified by main diagnosis at discharge into those with non-causative diagnosis and those with other diagnoses. Mortality per 100,000 within 8, 15 and 30 days and the corresponding hazard ratio (HR) and 95% confidence intervals (CI) were calculated for all causes of death and for selected causes of death in a time-dependent analysis.

RESULTS
The HRs of all causes of death for patients with a non-causative diagnosis were 0.64 (95% CI 0.41-1.01) within 8 days, 0.70 (95% CI 0.50-0.99) within 15 days, and 0.82 (95% CI 0.65-1.04) within 30 days as compared to those with a causative diagnosis. The HRs within 30 days among those with a non-causative diagnosis at discharge were 1.48 (95% CI 1.03-2.13) for malignant neoplasm, 3.72 (95% CI 1.44-9.60) for suicide, and 0.50 (95% CI 0.32-0.79) for diseases of the circulatory system.

CONCLUSION
Death within 8 days after discharge home from the ED is a rare event. Death of patients that occur shortly after discharge who had received a non-causative diagnosis as the main diagnosis may indicate a misjudgement of the patients' condition at that time.

mortality
suicide
non-causative diagnosis
malignant neoplasm
Disease of the circulatory system


Neonatal citalopram exposure decreases serotonergic fiber density in the olfactory bulb of male but not female adult rats.

Abstract: Manipulation of serotonin (5HT) during early development has been shown to induce long-lasting morphological changes within the raphe nuclear complex and serotonergic circuitry throughout the brain. Recent studies have demonstrated altered raphe-derived 5HT transporter (SERT) immunoreactive axonal expression in several cortical target sites after brief perinatal exposure to selective 5HT reuptake inhibitors such as citalopram (CTM). Since the serotonergic raphe nuclear complex projects to the olfactory bulb (OB) and perinatal 5HT disruption has been shown to disrupt olfactory behaviors, the goal of this study was to further investigate such developmental effects in the OB of CTM exposed animals. Male and female rat pups were exposed to CTM from postnatal day 8-21. After animals reach adulthood (>90 days), OB tissue sections were processed immunohistochemically for SERT antiserum. Our data revealed that the density of the SERT immunoreactive fibers decreased ~40% in the OB of CTM exposed male rats, but not female rats. Our findings support a broad and long-lasting change throughout most of the 5HT system, including the OB, after early manipulation of 5HT. Because dysfunction of the early 5HT system has been implicated in the etiology of neurodevelopmental disorders such as autism spectrum disorders (ASDs), these new findings may offer insight into the abnormal olfactory perception often noted in patients with ASD.

Zhang|Junlin|J|
Dennis|Katie A|KA|
Darling|Ryan D|RD|
Alzghoul|Loai|L|
Paul|Ian A|IA|
Simpson|Kimberly L|KL|
Lin|Rick C S|RC|

olfactory bulb
autism spectrum disorders
selective serotonin reuptake inhibitors
serotonin transporter
sexual dimorphism


Various diagnostic possibilities for zygomatic arch pain: Seven case reports and review of literature.

Abstract:
BACKGROUND
Pain of the zygomatic arch region is common among patients with orofacial pain, especially in those with temporomandibular disorder-related pain of a myogenic origin. Since zygomatic arch pain may occur due to various causes other than muscle pain, appropriate diagnosis and treatment planning is essential to ensure its successful management. Unfortunately, zygomatic arch pain has not been handled as an independent clinical feature until now, and studies have mainly focused on pain resulting from trauma and surgical procedures.

CASE SUMMARY
We describe 7 independent cases, all of which presented with the identical chief complaint of pain in the zygomatic arch region. However, the underlying causes were different for each, being myofascial pain, myositis, tooth crack, dental caries, sinusitis, neuropathic pain, and salivary gland tumor respectively. In this case report, the clinical features of each case are investigated and diseases to be considered in the diagnostic process are suggested, along with the diagnostic modalities (including computed tomography and magnetic resonance imaging) that can lead to the appropriate final diagnosis.

CONCLUSION
Zygomatic arch pain is a common complaint encountered in the orofacial pain clinic but may lead to misdiagnosis. Clinicians must have in-depth knowledge of the possible differential diagnoses and evaluation tools.

Zygomatic arch
Case report
Myositis
Sinusitis
Neuropathic pain
Salivary gland tumor
Odontogenic pain


Patient and Parent Perceptions of Rehabilitation Factors That Influence Outcomes After Anterior Cruciate Ligament Reconstruction and Clearance to Return to Sport in Adolescents and Young Adults.

Abstract:
BACKGROUND
Wide variation in outcomes after anterior cruciate ligament reconstruction (ACLR) exists among adolescents and young adults. However, little evidence is available regarding key rehabilitation factors that may be driving these differences.

OBJECTIVE
To explore patient and parent perceptions of key rehabilitation drivers related to outcomes after ACLR.

METHODS
In this qualitative study, which used an interpretive phenomenological methodology, semi-structured interviews were conducted with patients who had returned to sport after ACLR and with their parents. The interviews asked about respondents' experience with physical therapy and how it related to their outcomes after ACLR. The interviews were recorded, transcribed, and coded. Themes were then identified using open and axial coding processes.

RESULTS
There were 3 primary themes that patients and parents perceived as key factors influencing their rehabilitation outcomes after ACLR: (1) patient attributes (ie, motivation, confidence, accountability, access to resources, and social support), (2) physical therapist-patient relationship qualities (physical therapist as guide, motivator, booster of confidence, fosterer of perseverance, and coordinator of care), and (3) elements of the system (ie, availability and utilization of therapy visits, clinic environment, and coordination among care providers).

CONCLUSION
Patient and parent perspectives of key drivers that influence ACLR rehabilitation outcomes include patient, therapist, and system factors. Developing specific strategies to target these factors may enhance patient and parent perceptions of the experience. The awareness gained from these results provides a foundation for future studies examining how these factors affect outcomes and how to improve rehabilitation after ACLR.

LEVEL OF EVIDENCE
Therapy, level 3. J Orthop Sports Phys Ther 2019;49(8):576-583. Epub 13 Feb 2019. doi:10.2519/jospt.2019.8608.

Paterno|Mark V|MV|
Schmitt|Laura C|LC|
Thomas|Staci|S|
Duke|Nicholas|N|
Russo|Rebecca|R|
Quatman-Yates|Catherine C|CC|

D059549:Anterior Cruciate Ligament Reconstruction


Seroprevalence and associated risk factors of Mycoplasma agalactiae and investigation of coinfection with the caprine lentivirus in Rio Grande do Norte, Brazil.

Abstract: Contagious agalactia is a disease caused by Mycoplasma agalactiae that leads to a reduction or complete stop of milk production. Caprine arthritis encephalitis (CAE) is an infectious disease caused by a lentivirus of the Retroviridae family, member of the small ruminant lentivirus (SRLV) group. Although these diseases are caused by distinct pathogens, the clinical presentation is similar. Hence, this study aimed to perform a serological investigation, as well as to assess correlation between both diseases and risk factors associated in two mesoregions of Rio Grande do Norte, Brazil. Enzyme-linked immunosorbent assay (ELISA) was used for contagious agalactia and western blot for CAE. A total of 538 serum samples were used in this study that were collected from goats and sorted from a blood bank of the Brazilian Agricultural Research Corporation. Seroprevalence of M. agalactiae in flocks from Rio Grande do Norte was 7.8% (42/538). In both regions that were investigated, 25.9% (14/54) of farms had positive animals. CAE results revealed that 3.9% (21/538) of animals and 42.6% (23/54) of farms had this disease. Concerning risk factors, only sex and animal category presented significant relevance (P < 0.05) for contagious agalactia, in which females presented higher frequency of seropositive individuals (10.1%; 39/387). In the animal category, 4.3% (14/326) and 11.1% (36/323) of female breeders were positive for CAE and contagious agalactia, respectively, and significance was identified only in the latter (P < 0.05). In conclusion, there was no correlation between the investigated diseases, considering that no animal demonstrated antibodies for both pathogens.

Contagious agalactia
SRLV
Diagnosis
Prevalence


Role of the Keap1/Nrf2 pathway in neurodegenerative diseases.

Abstract: As the elderly population increases, a growing number of individuals suffer from age-associated neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). Oxidative stress is considered to play a crucial role in the pathogenesis of age-related diseases. The transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) is activated by oxidative stress and regulates the expression of a variety of antioxidant enzymes and proteins that exert cytoprotective effects against oxidative stress. Numerous studies have addressed the role of Nrf2 in age-related diseases, including neurodegenerative diseases, using animal or in vitro cell culture models. Here, we introduce the role of oxidative stress in the pathogenesis of neurodegenerative diseases and critically examine the recent findings concerning the role for Nrf2 in the amelioration of AD and PD. Nrf2 not only regulates antioxidant proteins but also regulates the genes associated with autophagy and nerve growth factor signaling. Current research unequivocally demonstrates that the activation of the Nrf2 pathway is a promising novel strategy for the prevention and modification of neurodegenerative diseases.

Yamazaki|Hiromi|H| Tanji|Kunikazu|K| Wakabayashi|Koichi|K| Matsuura|Shin|S| Itoh|Ken|K|

D047908:Intracellular Signaling Peptides and Proteins

D000072019:Kelch-Like ECH-Associated Protein 1

Nrf2
neurodegenerative disease
oxidative stress
ROS
dimethyl fumarate


Combination of low-dose mycophenolate mofetil with cyclosporine and methotrexate as GVHD prophylaxis in unrelated donor allogeneic stem cell transplantation.

Abstract: We report the results of HLA-matched unrelated donor allogeneic stem cell transplantation with new GVHD prophylaxis regimen consisted of cyclosporine, methotrexate and low-dose mycophenolate mofetil in 139 patients with hematologic malignancies. The incidence of grades II-IV and III-IV acute GVHD were 43.0% and 17.3%, respectively. The incidence of chronic GVHD was 42.1%, with 16.5% extensive grade. The cumulative incidence of transplant-related mortality at 100 days and 3 years were 7.9% and 29.7%, respectively. Three-year overall survival, disease-free survival and relapse incidence were 58.7%, 55.3% and 19.6%, respectively. These results suggest the new regime may be effective for the prophylaxis of acute and chronic GVHD in unrelated donor transplantation.

Zhu|Xiaoli|X| Lai|Xiaoyu|X| Luo|Yi|Y| Shi|Jimin|J| Tan|Yamin|Y| Zheng|Weiyan|W| He|Jingsong|J| Xie|Wanzhuo|W| Li|Li|L| Zhang|Jie|J| Ye|Xiujin|X| Lin|Maofang|M| Cai|Zhen|Z| Huang|He|H|

D018380:Hematopoietic Stem Cell Transplantation

Mycophenolate mofetil
GVHD
Unrelated donor
Allogeneic stem cell transplantation


Gross Dissection Time Values of Pathologists' Assistants Using Standardized Metrics.

Abstract:
OBJECTIVES
A validated and objective method to quantify the gross dissection time of pathologists' assistants (PAs) does not exist. We propose a method to calculate standardized work units (dissection time values [DTVs]) to monitor PA productivity.

METHODS
The Current Procedural Terminology system specifies six levels of specimen complexity encompassing 176 unique specimen types. Using our institutional dictionary, we designated all specimen types into a priori five levels of complexity based on expected dissection time. We hypothesized that expected time could be matched prospectively with the actual measured dissection time for all specimens. Dissection time data were collected prospectively for 12,775 specimens at two tertiary academic medical centers, and work effort was converted to a numeric DTV equivalent (number of minutes to dissect single specimen/420 minutes in a working day).

RESULTS
For 44 of 155 specimen types, measured dissection time for the five "levels" was lower than expected dissection (P < .0001). Accordingly, those 44 specimen types were reclassified to a lower level.

CONCLUSIONS
A numeric standard of the work effort for dissection time for 155 specimen types was developed, validated, and then used prospectively to monitor grossing efficiency of PA workforce.

Volel|Vladimir|V|
Kothari|Tarush|T|
Groppi|Diane|D|
Alexis|Claudine|C|
Ragnauth|Mike|M|
Qureshi|Raheela|R|
Entin|Amy|A|
Alexander|Amy|A|
Yaskiv|Oksana|O|
Crawford|James M|JM|
Kohn|Nina|N|
Bhuiya|Tawfiqul|T|

Productivity
Current Procedural Terminology (CPT)
Gross dissection time (DTV)
Gross examination
Pathologists’ assistants (PAs)
Surgical pathology


Smiles2Monomers: a link between chemical and biological structures for polymers.

Abstract:
BACKGROUND
The monomeric composition of polymers is powerful for structure comparison and synthetic biology, among others. Many databases give access to the atomic structure of compounds but the monomeric structure of polymers is often lacking. We have designed a smart algorithm, implemented in the tool Smiles2Monomers (s2m), to infer efficiently and accurately the monomeric structure of a polymer from its chemical structure.

RESULTS
Our strategy is divided into two steps: first, monomers are mapped on the atomic structure by an efficient subgraph-isomorphism algorithm ; second, the best tiling is computed so that non-overlapping monomers cover all the structure of the target polymer. The mapping is based on a Markovian index built by a dynamic programming algorithm. The index enables s2m to search quickly all the given monomers on a target polymer. After, a greedy algorithm combines the mapped monomers into a consistent monomeric structure. Finally, a local branch and cut algorithm refines the structure. We tested this method on two manually annotated databases of polymers and reconstructed the structures de novo with a sensitivity over 90 %. The average computation time per polymer is 2 s.

CONCLUSION
s2m automatically creates de novo monomeric annotations for polymers, efficiently in terms of time computation and sensitivity. s2m allowed us to detect annotation errors in the tested databases and to easily find the accurate structures. So, s2m could be integrated into the curation process of databases of small compounds to verify the current entries and accelerate the annotation of new polymers. The full method can be downloaded or accessed via a website for peptide-like polymers at http://bioinfo.lifl.fr/norine/smiles2monomers.jsp.Graphical abstract:.

Dufresne|Yoann|Y|0000-0002-0930-8920 Noé|Laurent|L| Leclère|Valérie|V| Pupin|Maude|M|

Polymer
Algorithm
Chemical structure
Monomer
Compound search
Graph
Peptide


Real-Time Fluorescence Imaging Using Indocyanine Green to Assess Therapeutic Effects of Near-Infrared Photoimmunotherapy in Tumor Model Mice.

Abstract:
BACKGROUND
Near-infrared photoimmunotherapy (NIR-PIT) is a cancer therapy that causes an increase in tumor perfusion, a phenomenon termed the super-enhanced permeability and retention effect. Currently, in vivo treatment efficacy of NIR-PIT is observable days after treatment, but monitoring would be improved by more acute detection of intratumor change. Fluorescence imaging may detect increased tumor perfusion immediately after treatment.

METHODS
In the first experiment, athymic nude mouse models bearing unilateral subcutaneous flank tumors were treated with either NIR-PIT or laser therapy only. In the second experiment, mice bearing bilateral flank tumors were treated with NIR-PIT only on the left-sided tumor. In both groups, immediately after treatment, indocyanine green was injected at different doses intravenously, and mice were monitored with the Shimadzu LIGHTVISION fluorescence imaging system for 1 hour.

RESULTS
Tumor-to-background ratio of fluorescence intensity increased over the 60 minutes of monitoring in treated mice but did not vary significantly in control mice. Tumor-to-background ratio was highest in the 1 mg kg-1 and 0.3 mg kg-1 doses. In mice with bilateral tumors, tumor-to-untreated tumor ratio increased similarly.

CONCLUSIONS
Acute changes in tumor perfusion after NIR-PIT can be detected by real-time fluorescence imaging.

cancer therapy
NIR fluorescence imaging
cancer imaging
cancer treatment efficacy
new optical instrumentation


Evaluating imbalances of adverse events during biosimilar development.

Abstract: Biosimilars are designed to be highly similar to approved or licensed (reference) biologics and are evaluated based on the totality of evidence from extensive analytical, nonclinical and clinical studies. As part of the stepwise approach recommended by regulatory agencies, the first step in the clinical evaluation of biosimilarity is to conduct a pharmacokinetics similarity study in which the potential biosimilar is compared with the reference product. In the context of biosimilar development, a pharmacokinetics similarity study is not necessarily designed for a comparative assessment of safety. Development of PF-05280014, a potential biosimilar to trastuzumab, illustrates how a numerical imbalance in an adverse event in a small pharmacokinetics study can raise questions on safety that may require additional clinical trials.

Vana|Alicia M|AM|
Freyman|Amy W|AW|
Reich|Steven D|SD|
Yin|Donghua|D|
Li|Ruifeng|R|
Anderson|Scott|S|
Jacobs|Ira A|IA|
Zacharchuk|Charles M|CM|
Ewesuedo|Reginald|R|

D017321:Clinical Trials, Phase I as Topic

D016032:Randomized Controlled Trials as Topic

Biosimilar
safety
trastuzumab
HER2
breast cancer


Impact of inclusion rates of crossbred phenotypes and genotypes in nucleus selection programs.

Abstract: Numerous methods have been suggested to incorporate crossbred (CB) phenotypes and genotypes into swine selection programs, yet little research has focused on the implicit trade-off decisions between generating data at the nucleus or commercial level. The aim of this study was to investigate the impact of altering the proportion of purebred (PB) and CB phenotypes and genotypes in genetic evaluations on the response to selection of CB performance. Assuming CB and PB performance with moderate heritabilities (h2=0.4), a three-breed swine crossbreeding scheme was simulated and selection was practiced for six generations, where the goal was to increase CB performance. Phenotypes, genotypes, and pedigrees for three PB breeds (25 and 175 mating males and females for each breed, respectively), F1 crosses (400 mating females), and terminal cross progeny (2,500) were simulated. The genome consisted of 18 chromosomes with 1,800 quantitative trait loci and 72k single nucleotide polymorphism (SNP) markers. Selection was performed in PB breeds using estimated breeding value for each phenotyping/genotyping strategy. Strategies investigated were: 1) increasing the proportion of CB with genotypes, phenotypes, and sire pedigree relationships, 2) decreasing the proportion of PB phenotypes and genotypes, and 3) altering the genetic correlation between PB and CB performance (rpc). Each unique rpc scenario and data collection strategy was replicated 10 times. Results showed that including CB data improved the CB performance regardless of  rpc or data collection strategy compared with when no CB data were included. Compared with using only PB information, including 10% of CB progeny per generation with sire pedigrees and phenotypes increased the response in CB phenotype by 134%, 55%, 33%, 23%, and 21% when rpc was 0.1, 0.3, 0.5, 0.7, and 0.9, respectively. When the same 10% of CB progeny were also genotyped, CB performance increased by 243%, 54%, 38%, 23%, and 20% when the rpc was 0.1, 0.3, 0.5, 0.7, and 0.9, respectively, compared with when no CB data were utilized. Minimal change was observed in the average CB phenotype when PB phenotypes were included or proportionally removed when CB were genotyped. Removal of both PB phenotypes and genotypes when CB were genotyped greatly reduced the response in CB performance. In practice, the optimal inclusion rate of CB and PB data depends upon the genetic correlation between CB and PB animals and the expense of additional CB data collection compared with the economic benefit associated with increased CB performance.

See|Garrett M|GM|
Mote|Benny E|BE|
Spangler|Matthew L|ML|

swine
genotyping strategy
commercial data
phenotyping strategy


Sini decoction ameliorates interrelated lung injury in septic mice by modulating the composition of gut microbiota.

Abstract: Our work used cecal ligation and puncture (CLP) mice model and 16S rDNA sequencing to explore whether the therapeutic mechanism of Sini Decoction (SND) on sepsis was related to the intestinal flora currently of concern. Twenty-four hours after surgery, tissues and serum from three groups (Control, CLP and CLP + SND) were collected for further analysis and colon contents were isolated for 16S rDNA analysis. Mortality, histological examination and inflammatory cytokines levels confirmed that the sepsis model was induced successfully and resulted in serious pathological damage, while all of these could be reversed by SND. In intestinal flora analysis, the microbial richness and abundance were recovered after SND treatment. Furthermore, at the phylum level, the abundance of Proteobacteria showed drastic increase after CLP. Similarly, CLP surgery significantly disrupted the balance of intestinal flora, with a huge increase of Escherichia-Shigella, a Gram-negative genus that might release lipopolysaccharide (LPS) and other genera. And these shifts could be defused by SND, indicating its function of regulating gut microbiota. This study demonstrates that SND could ameliorate the symptoms and pathology associated with sepsis in CLP model via modulating the flora in intestinal tract, which enriches a possible mechanism of SND's therapeutic effect.

Wang|Wanqiu|W| Chen|Qiuhua|Q| Yang|Xiaoting|X| Wu|Jie|J| Huang|Fengjie|F|

Sini decoction
Gut microbiota
Cecal ligation and puncture
Sepsis


Management strategies of neonatal jaundice during the coronavirus disease 2019 outbreak.

Abstract: The outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV) has become a most challenging health emergency. Owing to rigorous quarantine and control measures taken in China, routine neonatal health surveillance and follow-up have become challenging. Without follow-up surveillance, some rapid and progressive newborn diseases, such as bilirubin encephalopathy, may be ignored. The characteristics of onset age of kernicterus suggest that monitoring of bilirubin level at home provides a useful way to alert hospital visits and to prevent the development of extremely hyperbilirubinemia. Therefore, we developed an online follow-up program for convenient monitoring of bilirubin level of newborns that is based on our practical experiences. The aim is to make our management strategies of neonatal jaundice tailored to the infection prevention and control during the COVID-19 epidemic.

Ma|Xiao-Lu|XL| Chen|Zheng|Z| Zhu|Jia-Jun|JJ| Shen|Xiao-Xia|XX| Wu|Ming-Yuan|MY| Shi|Li-Ping|LP| Du|Li-Zhong|LZ| Fu|Jun-Fen|JF| Shu|Qiang|Q|

Follow-up
Newborn
Hyperbilirubinemia
Internet hospital
New coronavirus pneumonia


Is the prevalence of Clostridium difficile in animals underestimated?

Abstract: Reported prevalence rates of Clostridium difficile infection in animals differ considerably depending on the nature of the study and the population surveyed. The methods used to recover this organism from faecal samples may account for some of the prevalence variation. The objective of this study was to assess the performance of two different methods of detecting C. difficile in animal faeces in comparison with a conventional isolation procedure ('ethanol shock' of faecal samples followed by culture on a single plate of solid selective medium). Samples were obtained from two populations of pigs where the expected prevalence rate of C. difficile infection was anticipated to differ, namely, 'high prevalence' (<7-day old piglets) and 'low prevalence' (2-3-month old pigs). The first alternative detection method required culturing faecal samples on 10 (instead of one) plate of solid selective medium after ethanol shock, while the second method included an intermediate enrichment step in selective broth prior to ethanol shock and subsequent plating. Both alternative methods considerably increased bacterial recovery in tested samples from both surveyed populations and highlighted the existence of a considerable proportion (≥ 22%) of false negatives. The results confirm previous suggestions that the procedure used to isolate C. difficile can have a significant impact on prevalence data for this pathogen.

Blanco|José L|JL|
Álvarez-Pérez|Sergio|S|
García|Marta E|ME|

Prevalence
Clostridium difficile
Enrichment
Bacteriological culture
Recovery rate


Novel aminoarylcysteine adducts in globin of rats dosed with naphthylamine and nitronaphthalene isomers.

Abstract: Novel aminonaphthylcysteine (ANC) adducts, formed via naphthylnitrenium ions and/or their metabolic precursors in the biotransformation of naphthylamines (NA) and nitronaphthalenes (NN), were identified and quantified in globin of rats dosed intraperitoneally with 0.16 mmol/kg b.w. of 1-NA, 1-NN, 2-NA and 2-NN. Using HPLC-ESI-MS2 analysis of the globin hydrolysates, S-(1-amino-2-naphthyl)cysteine (1A2NC) together with S-(4-amino-1-naphthyl)cysteine (4A1NC) were found in rats given 1-NA or 1-NN, and S-(2-amino-1-naphthyl)cysteine (2A1NC) in those given 2-NA or 2-NN. The highest level of ANC was produced by the most mutagenic and carcinogenic isomer 2-NA (35.8 ± 5.4 nmol/g globin). The ratio of ANC adduct levels for 1-NA, 1-NN, 2-NA and 2-NN was 1:2:100:3, respectively. Notably, the ratio of 1A2NC:4A1NC in globin of rats dosed with 1-NA and 1-NN differed significantly (2:98 versus 16:84 respectively), indicating differences in mechanism of the adduct formation. Moreover, aminonaphthylmercapturic acids, formed via conjugation of naphthylnitrenium ions and/or their metabolic precursors with glutathione, were identified in the rat urine. Their amounts excreted after dosing rats with 1-NA, 1-NN, 2-NA and 2-NN were in the ratio 1:100:40:2, respectively. For all four compounds tested, haemoglobin binding index for ANC was several-fold higher than that for the sulphinamide adducts, generated via nitrosoarene metabolites. Due to involvement of electrophilic intermediates in their formation, ANC adducts in globin may become toxicologically more relevant biomarkers of cumulative exposure to carcinogenic or non-carcinogenic arylamines and nitroarenes than the currently used sulphinamide adducts.

Linhart|Igor|I|0000-0003-2682-4326 Hanzlíková|Iveta|I| Mráz|Jaroslav|J|0000-0002-9984-5593 Dušková|Šárka|Š| Tvrdíková|Monika|M| Vachová|Hana|H|

Carcinogens
Biomarker
Arylamines
Nitroarenes
Arylnitrenium ions
Globin adducts


A hermeneutic phenomenological understanding of men's healing from childhood maltreatment.

Abstract:
PURPOSE
To describe and interpret men's experience of healing from childhood maltreatment.

DESIGN
Hermeneutic phenomenological.

METHOD
In-depth interviews. Community-based purposive, maximum variation sampling approach. Recruitment occurred through posting flyers and advertisements. Verbatim data were analyzed and themes of the meaning of healing were identified.

FINDINGS
The meaning of healing was interpreted as "moving beyond suffering." Five themes were identified to capture the multidimensional nature of the phenomenon: (a) breaking through the masculine veneer, (b) finding meaning, (c) choosing to live well, (d) caring for the self using holistic healing methods, and (e) engaging in humanizing relationships.

CONCLUSIONS
Men who survived childhood maltreatment have needs to heal holistically mind, body, and spirit. Meeting their needs requires the provision of highly compassionate humanistic healing environments and healing-promotive nursing care.

Willis|Danny G|DG|
Rhodes|Alison M|AM|
Dionne-Odom|James N|JN|
Lee|Kayoung|K|
Terreri|Pamela|P|

healing
adults
health promotion
other (multiple modalities)


The Case for Culturally Responsive Teaching in Pharmacy Curricula.

Abstract: Cultural diversity training in pharmacy education has evolved from standalone lectures to longitudinal courses, service-learning initiatives, rotation experiences and global health opportunities. Cultural competency frameworks have served as the scaffold for cultural diversity training, yet educators in other health care disciplines have called into question the utility of such frameworks and offered cultural humility as an alternative to foster development and lifelong learning. In order to implement and assess outcomes tied to cultural diversity successfully, this commentary discusses the five elements of culturally responsive teaching that will provide the tools necessary to integrate cultural humility across pharmacy curricula. In addition, we address how to approach faculty development to avoid common maladaptations in pedagogical movements and conclude with addressing the salient objectives to evaluate gains in student, institutional, and societal outcomes.

culturally responsive teaching
cultural diversity
cultural competency
cultural humility


Subclinical anaplasmosis in camel (Camelus dromedarius) and its successful therapeutic management.

Abstract: On the Indian sub continent, dromedarian camel -'the ship of the desert' is an important constituent of the socio economic life style of nomadic owners in the semi arid to arid ecosystems. The animal suffers from a few parasitic diseases viz. surra, coccidiosis, sarcocystis, gastro intestinal concurrent metazoan infections, mange, nasal bots and ticks infestations. However, anaplasmosis in camel has not been reported so far from the Indian subcontinent. Systematic investigations of a 7 year male Jaisalmeri camel, with a clinical history of dullness, progressive loss of condition and stamina revealed subclinical Anaplasma marginale infection. The animal had depressed haematological indices, dry and constipated bowels, pale and icteric conjunctiva suggestive of anaemia. The animal positively responded to the specific integrated therapy. Reexamination of the animal on day 21 post-therapy revealed depressed haematological indices restored to normal levels and the erythrocytes were free from the pathogen. Neglected attention, poor and/or underreporting of camel diseases vis-a-vis economic significance of the versatile animal has been discussed. This appears to be the pioneer documentation of anaplasmosis in camels from Indian subcontinent.

Sudan|Vikrant|V|
Sharma|R L|RL|
Borah|M K|MK|

Subclinical anaplasmosis
Dromedarian camel
Anaplasma marginale
Pioneer documentation


Between and Within Sexual Identity-Group Differences in Asthma Prevalence in the United States.

Abstract:
BACKGROUND
Although prior studies have established the association of asthma with smoking and obesity, literature on difference-in-differences analyses involving sexual identity is sparse. Therefore, this study aimed to examine the between and within sexual identity-group differences in asthma prevalence among individuals who smoke and are obese.

METHODS
We aggregated the 2017-2019 National Survey on Drug Use and Health data on adults (N = 128,319) to perform weighted multivariable logistic regression analysis and marginal estimates and marginsplot to determine asthma prevalence by sexual identity and the status of smoking and obesity.

RESULTS
About 66% of the study population reported having asthma. Among the individuals with asthma, 42% were obese, 10% were daily cigarette smokers, and 6% identified as bisexual persons. Lesbian/gay daily smokers (86%) or former smokers (75%) had a higher probability of having asthma than bisexual (daily smokers = 78% vs former smokers = 72%) and heterosexual (daily smokers = 68% vs former smokers = 65%) persons. Within each sexual identity subgroup, daily smokers (68-86%) had the highest probability of asthma. Obese bisexual (73%) or lesbian/gay (72%) persons had higher probabilities of having asthma than heterosexual persons (69%). Obese (73%) or overweight (72%) bisexual (compared to normal weight = 70% or underweight = 51%) and obese (69%) or overweight (65%) heterosexual (compared to normal weight = 62% or underweight = 57%) persons had the highest probabilities of having asthma within their groups, whereas overweight persons (overweight = 81% vs underweight = 79%, normal weight = 78%, and obese = 72%) had the highest probabilities within lesbian/gay persons.

CONCLUSIONS
Smoking and obesity show heightened odds for asthma, with significant odds for sexual minorities in asthma diagnosis relative to heterosexuals. These findings provide formative information for future longitudinal and experimental studies to explore these mechanisms of asthma risks among sexual and gender minorities.

Adzrago|David|D|
Nyarko|Samuel H|SH|
Ananaba|Nnenna|N|
Asare|Matt|M|
Odame|Emmanuel|E|
Jones|Antwan|A|
Paul|Timir K|TK|
Mamudu|Hadii M|HM|

asthma
smoking
obesity
sexual and gender minorities


Suicidality in Chronic Illness: An Overview of Cognitive-Affective and Interpersonal Factors.

Abstract: Suicide rates are elevated in individuals with chronic illness, yet few studies have examined risk factors for suicide in this population. Drawing from theoretical models and risk factors identified in the suicide literature more broadly, this article provides a conceptual overview of cognitive (e.g., pain catastrophizing, self-criticism), affective (e.g., emotion dysregulation), interpersonal (e.g., perceived burdensomeness, thwarted belongingness, critical expressed emotion), and behavioral factors that may contribute, at least in part, to the link between chronic illness, and illness-specific factors, and suicidal thoughts and behaviors. We also outline several avenues for future research in this area and provide specific considerations and recommendations for the screening, assessment, and initial intervention of suicide risk within individuals with chronic health conditions.

Rogers|Megan L|ML|0000-0002-4969-7035
Joiner|Thomas E|TE|
Shahar|Golan|G|

Suicide
Chronic illness
Health
Disease
Mechanisms


A Plant Leaf Geometric Parameter Measurement System Based on the Android Platform.

Abstract: Automatic and efficient plant leaf geometry parameter measurement offers useful information for plant management. The objective of this study was to develop an efficient and effective leaf geometry parameter measurement system based on the Android phone platform. The Android mobile phone was used to process and measure geometric parameters of the leaf, such as length, width, perimeter, and area. First, initial leaf images were pre-processed by some image algorithms, then distortion calibration was proposed to eliminate image distortion. Next, a method for calculating leaf parameters by using the positive circumscribed rectangle of the leaf as a reference object was proposed to improve the measurement accuracy. The results demonstrated that the test distances from 235 to 260 mm and angles from 0 to 45 degrees had little influence on the leafs' geometric parameters. Both lab and outdoor measurements of leaf parameters showed that the developed method and the standard method were highly correlated. In addition, for the same leaf, the results of different mobile phone measurements were not significantly different. The leaf geometry parameter measurement system based on the Android phone platform used for this study could produce high accuracy measurements for leaf geometry parameters.

Liu|Haiyun|H| Ma|Xu|X| Tao|Ming|M| Deng|Ruoling|R| Bangura|Kemoh|K| Deng|Xiangwu|X| Liu|Chuang|C| Qi|Long|L|

plant leaf
Android system
dynamic reference
image analysis


Multicomponent, nonpharmacological delirium interventions for older inpatients : A scoping review.

Abstract:
BACKGROUND
Older people represent a risk group for acquiring or further development of delirium during hospitalization, therefore requiring suitable nonpharmacological delirium interventions.

OBJECTIVE
This scoping review analyzed nonpharmacological intervention programs for older inpatients with or without cognitive decline on regular or acute geriatric wards to present the range of interventions.

METHODS
A systematic literature search was conducted using scientific databases. A total of 4652 records were screened by two independent reviewers, leaving 81 eligible articles for full-text screening and 25 studies were finally included. Inclusion criteria were older patients ≥65 years in regular or acute geriatric wards and nonpharmacological multicomponent interventions.

RESULTS
More than a half of the included studies (14, 56%) recruited patients with pre-existing cognitive decline as part of the study population and 12% focused exclusively on patients with cognitive decline. On average 11 intervention components were integrated in the programs and two programs included full coverage of all 18 identified components.

CONCLUSION
Only few programs were described for older inpatients and even fewer regarding pre-existing cognitive decline. The low numbers of interventions and data heterogeneity restricted the assessment of outcomes; however, delirium incidence, as reported by two thirds of the studies was reduced by nonpharmacological multicomponent interventions.

Hospitalization
Cognitive decline
Epidemiology
Literature review
Prevalence


Machine Learning Methods as a Tool for Predicting Risk of Illness Applying Next-Generation Sequencing Data.

Abstract: Next-generation sequencing (NGS) data present an untapped potential to improve microbial risk assessment (MRA) through increased specificity and redefinition of the hazard. Most of the MRA models do not account for differences in survivability and virulence among strains. The potential of machine learning algorithms for predicting the risk/health burden at the population level while inputting large and complex NGS data was explored with Listeria monocytogenes as a case study. Listeria data consisted of a percentage similarity matrix from genome assemblies of 38 and 207 strains of clinical and food origin, respectively. Basic Local Alignment (BLAST) was used to align the assemblies against a database of 136 virulence and stress resistance genes. The outcome variable was frequency of illness, which is the percentage of reported cases associated with each strain. These frequency data were discretized into seven ordinal outcome categories and used for supervised machine learning and model selection from five ensemble algorithms. There was no significant difference in accuracy between the models, and support vector machine with linear kernel was chosen for further inference (accuracy of 89% [95% CI: 68%, 97%]). The virulence genes FAM002725, FAM002728, FAM002729, InlF, InlJ, Inlk, IisY, IisD, IisX, IisH, IisB, lmo2026, and FAM003296 were important predictors of higher frequency of illness. InlF was uniquely truncated in the sequence type 121 strains. Most important risk predictor genes occurred at highest prevalence among strains from ready-to-eat, dairy, and composite foods. We foresee that the findings and approaches described offer the potential for rethinking the current approaches in MRA.

Njage|Patrick Murigu Kamau|PMK|
Henri|Clementine|C|
Leekitcharoenphon|Pimlapas|P|
Mistou|Michel-Yves|MY|
Hendriksen|Rene S|RS|
Hald|Tine|T|

machine learning
microbial risk assessment
Listeria monocytogenes
support vector machines
whole genome sequencing


Favorable effect of glycoprotein IIbIIIa inhibitors among STEMI patients treated with primary PCI and incomplete ST resolution.

Abstract: Incomplete ST resolution after primary percutaneous coronary interventions (pPCI) in STEMI patients is a well known prognostic marker, associated with the occurrence of microvascular obstruction and increased mortality. The effects of the use of glycoprotein IIbIIIa inhibitors (GPIs) in this peculiar subset of high- risk patients is still unknown. The aim of the present study was to assess whether the GPIs administration would result in improved outcome in ST elevation myocardial infarction (STEMI) patients with incomplete ST resolution (ISTR).All consecutive STEMI patients who underwent pPCI at our hospital between 2005 and 2014 were enrolled (n = 2001). ST resolution was defined as incomplete with a < 70% resolution of initial ST shift. Mortality analyses were performed by Kaplan-Meier curves, multivariable analysis through Cox regressions and propensity matching score. The incidence of ISTR was 29% (n = 592). Among ISTR patients, GPIs use was an independent predictor of better prognosis (HR 0.39, 95% CI 0.16-0.96, p < 0.04). Propensity matched analysis confirmed that the use of GPIs was associated with a lower 30-day (6.1% vs 13.4%, p = 0.02) and 1-year (8.4% vs 15.1%, p = 0.045) mortality. STEMI patients treated with pPCI and presenting ISTR show a poor outcome. The use of GPIs in these patients is associated with improved survival at 30 days and at 1 year; the causes for these favorable effects remain speculative and could be related to the development and evolution of microvascular obstruction.

D019039:Platelet Glycoprotein GPIIb-IIIa Complex

D000072657:ST Elevation Myocardial Infarction


The complete chloroplast genome of Callicarpa bodinieri (Lamiales, Lamiaceae), an ornamental and medicinal plant from Chongqing, China.

Abstract: Plants classified to the genus Callicarpa L. have important medicinal and ornamental value. Here, we report and characterize the complete chloroplast (cp) genome of C. bodinieri to provide molecular basis for the further studies on the phylogeny analysis of this genus. The cp genome is 154,183 bp in length and is organized with a typical quadripartite structure, containing two inverted repeats of 25,701 bp separated by a large single-copy region of 84,956 bp and a small single-copy region of 17,825 bp. The cp genome of C. bodinieri contains 112 distinct genes, including 78 protein-coding, 30 tRNAs and 4 rRNAs genes. The phylogenetic analysis showed that C. bodinieri is fully resolved in a clade with C. nudiflora, sister to the clade of C. formosana and C. longifolia var. floccosa.

Wang|Chao-Ying|CY| Luo|Ji-Hong|JH| He|Hui-Liu|HL| Wang|Qian|Q|

chloroplast genome
Callicarpa bodinieri
Lamiaceae
phylogenetic analysis


Left atrial appendage closure.

Abstract: Stroke or systemic embolism is a devastating consequence of atrial fibrillation (AF) due to thrombus formation in the left atrial appendage (LAA). AF causes thrombus formation in the LAA due to both the loss of atrial systole and the unique anatomic features of the LAA. Oral anticoagulation is a well established and effective therapy to reduce the risk of stroke in AF patients, albeit with a risk of bleeding. LAA closure is a possible alternative to oral anticoagulation in the prevention of stroke or systemic embolism in AF.

Left atrial appendage
Left atrial appendage closure
Atrial fibrillation


Intersectionality in the Liminal Space: Researching Caribbean Women's Health in the UK Context.

Abstract: African Caribbean women in the UK who are diagnosed with chronic illnesses that are related to overweight and obesity are more likely to experience poorer outcomes than their White British counterparts. It is then important to increase understandings of how women from this ethnic group perceive health with relation to body shape and size so that interventions can be developed to prevent the development of such conditions and to improve outcomes. As such, it is important to develop research methodology that encourages participation in health research from African Caribbean women and enables the capture of in-depth data that gives insight into the nuances of health understandings related to the body and the social realities in which they exist. This paper details the methodological framework of The Big Talk project, an investigation that sought to develop a novel approach to conducting health research with seldom heard communities. The concept of intersectionality, as used in Critical Race Theory, was applied as a theoretical tool for exploring the dynamics of societal power and where this power intersects across the lived realities of race, ethnicity, gender, sexuality, (dis)ability, and class. For this research, these intersections are explored for African Caribbean women and how they relate to concepts of health, body shape, and size. This research study was conducted in spaces identified as liminal spaces for African Caribbean women: talk radio programmes; hairdressing salons and; local community groups. A Black feminist epistemological approach was used to facilitate the collection of data. The data that emerged from these liminal spaces are not necessarily definitive answers on health for African Caribbean women, but rather illuminate alternative ways of understanding the social world from the perspective of those subject to power. This phenomenon makes liminal spaces intersectional in their construction and in taking such an approach to analysis could enable finely grained details of discourses regarding health, wellness and the body to be gathered. The importance of this understanding can help to improve preventive health interventions for African Caribbean women.

Andrews|Nicole|N| Greenfield|Sheila|S| Drever|William|W| Redwood|Sabi|S|

intersectionality
liminality
African Caribbean women
obesity
ethnicity
chronic health
qualitative methodology


A complex postnatal mental health intervention: Australian translational formative evaluation.

Abstract: Reducing the burden of postnatal maternal mental health problems is an international public health priority. We developed What Were We Thinking (WWWT), a psychoeducation programme for primary postnatal health care that addresses known but neglected risks. We then demonstrated evidence of its effects in a before-and-after controlled study in preventing maternal postnatal mental health problems among women without a psychiatric history participating in the intervention compared to usual care (AOR 0.43; 95% CI 0.21, 0.89) when conducted by specialist nurses. Testing its effectiveness when implemented in routine primary care requires changes at practitioner, organizational and health system levels. This paper describes a programme of translational formative evaluation to inform the protocol for a cluster RCT. Following the UK Medical Research Council (MRC) Guidance for evaluating complex interventions, we conducted a translational formative evaluation using mixed methods. Collection and analysis of postnatal health service documents, semi-structured interviews, group discussions and an online survey were used to investigate service provision, consumers' needs and expectations, clinicians' attitudes and clinical practice, and the implications for health service delivery. Participants were expectant parents, health care providers, health service managers and government policy makers. Results documented current clinical practice, staff training needs, necessary service modifications to standardize advice to parents and include fathers, key priorities and drivers of government health policy, and informed a model of costs and expected health and social outcomes. Implementation of WWWT into routine postnatal care requires adjustments to clinical practice. Staff training, modifications to service opening hours and economic implications for the health system also need to be considered. The MRC Guidance for developing and evaluating complex interventions is a useful framework for conceptualizing and reporting translational formative evaluation, which is an essential step in the evidence trajectory. The results of the evaluation will inform the protocol for a cluster RCT of WWWT and associated health economic evaluation.

Rowe|Heather J|HJ|
Wynter|Karen H|KH|
Burns|Joanna K|JK|
Fisher|Jane R W|JRW|

evaluation
prevention
implementation
perinatal mental health
research translation


Management of adverse effects/toxicity of ibrutinib.

Abstract: Bruton tyrosine kinase signaling (BTK) is critical step for B-cell development and immunoglobulin synthesis. Ibrutinib is an orally bioavailable bruton tyrosine kinase inhibitor (BTKi) and forms an irreversible covalent bound to BTK at the Cysteine-481 residue. Ibrutinib has been approved by FDA for the treatment of mantle cell lymphoma, chronic lymphocytic leukemia, Waldenstrom's macroglobulinemia, marginal zone lymphoma and chronic graft-versus-host disease in allogeneic stem cell transplantation. Ibrutinib is generally well tolerated drug with rapid and durable responses but has some side events. The most common side effects are diarrhea, upper respiratory tract infection, bleeding, fatigue and cardiac side effects. These events are generally mild (grade I-II). However atrial fibrillation (AF) and bleeding are important and may be grade III or higher side effects require strict monitoring. Here side effects of ibrutinib have been summarized and important considerations in the management of these adverse events have been reviewed.

D064420:Drug-Related Side Effects and Adverse Reactions

Adverse effect
Ibrutinib
Diarrhea
Infection
Atrial fibrillation
Bruising
Skin reactions


Variation in the obesity risk gene FTO determines the postprandial cerebral processing of food stimuli in the prefrontal cortex.

Abstract: Variation in FTO is the strongest genetic determinant of body weight and has recently been linked with impaired neural processing of food stimuli. However, whether this brain-expressed gene affects neuronal processing of food-related stimuli after ingestion is still poorly understood. In this study, twenty-four participants were examined before, 30 and 120 min after ingesting 75 g of glucose solution or water on two separate days. Functional magnetic resonance imaging (fMRI) during visual food presentation was performed. All participants were genotyped for FTO SNP rs8050136. We detected significant differences between FTO genotypes in the prefrontal cortex 30 min post-glucose load in BOLD-response to food pictures (p=0.0017), while no differences were detected in response to water ingestion or 120 min post-glucose load. Since the prefrontal cortex plays a major role in the inhibitory control of eating, we propose that reduced postprandial activity in FTO risk allele carriers contributes to overeating and obesity.

Heni|Martin|M| Kullmann|Stephanie|S| Veit|Ralf|R| Ketterer|Caroline|C| Frank|Sabine|S| Machicao|Fausto|F| Staiger|Harald|H| Häring|Hans-Ulrich|HU| Preissl|Hubert|H| Fritsche|Andreas|A|


Resilience in Women who Experience Domestic Violence.

Abstract: Violence in the family constitutes a serious social and psychological problem with harmful consequences leading, among others, to changes in the psychological functioning of the victim and, secondarily, also the perpetrator. The aim of this study was to examine resilience in women experiencing domestic violence. The "Ego Resiliency Scale" (ERS) was used to study the group of women suffering domestic violence. The study group included 52 women aged 30-65 years (mean age: 40.15) using assistance of the Crisis Intervention Centre due to experienced domestic violence. They most often reported suffering psychological and physical violence, with the husband or intimate partner being the most common perpetrator. Study women experiencing domestic violence obtained significantly lower scores on the ERS. The lowest scores on the ERS were achieved by women suffering paternal violence, while the highest - by women experiencing violence on the part of the intimate partner. Resilience of study women suffering domestic violence was lower than resilience of the general population, i.e. individuals not experiencing domestic violence. Suffered violence inflicted by the father exerted the greatest adverse impact on resilience. It seems advisable to consider resilience in the process of providing women experiencing domestic violence with psychosocial help.


Novel Polymethoxylated Chalcones as Potential Compounds Against KRAS-Mutant Colorectal Cancers.

Abstract:
BACKGROUND/OBJECTIVE
KRAS-mutant colorectal cancers (CRC) are tumors that are associated with poor prognosis. However, no effective treatments are available to target them. Therefore, we designed and synthesized novel chalcone analogs, small organic molecules, to investigate their effects on KRAS-mutant CRC cells.

METHODS
Fourteen new chalcone analogs were synthesized, optimized, characterized, and tested against two KRAS-mutant CRC cell lines (HCT-116 and LoVo), one p-53 and BRAF mutant CRC cell line (HT-29) and one normal immortalized colon cells (NCE-1 E6/E7). Effects on cell viability, apoptosis, cell cycle, migration, colony formation, EMT, and angiogenesis were investigated.

RESULTS
Compounds 3 and 14 were the most effective. Compound 3 showed potent activity against HCT-116 and LoVo cell lines (GI50 of 6.10 μM and 7.00 μM, respectively). While compound 14 showed GI50 of 8.60 μM and 8.80 μM on HCT-116 and LoVo cell lines, respectively. Both compounds were approximately 2-3 times more selective toward cancer cells rather than normal colon cells. Compound 3 was effective in inducing apoptosis in HCT-116 cells via Bax upregulation and Bcl-2 downregulation. Invasion and metastasis of KRAS-mutant cells were modulated by compounds 3 and 14 through significant inhibition of cell migration and the prevention of colony formation. In addition, they reversed EMT by downregulation of EMT markers (vimentin, fascin, and β- catenin) and upregulation of cell-cell adhesion marker, E-cadherin. Furthermore, compounds 3 and 14 had significantly inhibited angiogenesis in ovo.

CONCLUSION
Compounds 3 and 14 represent potent and selective leads for KRAS-mutant CRC cells, thus, further in vitro and in vivo studies are necessary to confirm their effect on KRAS-mutant CRCs.

Mahmoud|Alaa|A|
Elkhalifa|Dana|D|
Alali|Feras|F|
Al Moustafa|Ala-Eddin|AE|
Khalil|Ashraf|A|

Chalcone
colorectal cancer
analogs
KRAS mutation
epithelial-mesenchymal transition (EMT)
metastasis.


Endoscopic Evaluation of Angiogenesis in the Large Airways of Horses with Heaves Using Narrow Band Imaging.

Abstract:
BACKGROUND
Heaves is a severe debilitating condition of horses, characterized by lower airway inflammation and permanent structural changes of the bronchial wall. Chronic inflammation promotes the formation of new vessels, a phenomenon known as angiogenesis. Narrow band imaging (NBI) endoscopy is a noninvasive technique that enhances the visualization of submucosal vessels, and commonly is employed for the study of angiogenesis in human patients.

OBJECTIVES
Using NBI, we aimed to determine whether or not the central airways of horses with heaves undergo angiogenesis.

ANIMALS
Horses with heaves during exacerbation of the disease (n = 5) and healthy controls (n = 6).

METHODS
A library of NBI images was established from previously recorded videoendoscopies. Images were acquired by an operator blinded to horse ID. Images were obtained from 3 sites: 130 from the trachea (14 ± 9.3 [mean ± SD] images per horse with heaves and 10 ± 5.4 from controls; P = .45), 58 from the carina (5.4 ± 3.2 from horses with heaves and 5.2 ± 2.8 fromn controls; P > .99) and 167 from the intermediate bronchi (17.8 ± 6.7 from horses with heaves and 13 ± 5.6 from controls; P = .17). Using dedicated stereology software (NewCAST, Visiopharm; Denmark), the volume density of superficial and deep vessels was calculated blindly by point counting at each site for all horses.

RESULTS
In the trachea, the volume density of superficial vessels was increased in horses with heaves compared to controls (P = .02). No difference was found between groups for the volume density of both superficial and deep vessels at the carina or intermediate bronchi.

CONCLUSION AND CLINICAL RELEVANCE
NBI imaging of the airways was easily performed in standing sedated horses.

Blood vessels
Equine Asthma
Recurrent airway obstruction


Imaging of Chemokine Receptor 4 Expression in Neuroendocrine Tumors - a Triple Tracer Comparative Approach.

Abstract: C-X-C motif chemokine receptor 4 (CXCR4) and somatostatin receptors (SSTR) are overexpressed in gastro-entero-pancreatic neuroendocrine tumors (GEP-NET). In this study, we aimed to elucidate the feasibility of non-invasive CXCR4 positron emission tomography/computed tomography (PET/CT) imaging in GEP-NET patients using [68Ga]Pentixafor in comparison to 68Ga-DOTA-D-Phe-Tyr3-octreotide ([68Ga]DOTATOC) and 18F-fluorodeoxyglucose ([18F]FDG). Twelve patients with histologically proven GEP-NET (3xG1, 4xG2, 5xG3) underwent [68Ga]DOTATOC, [18F]FDG, and [68Ga]Pentixafor PET/CT for staging and planning of the therapeutic management. Scans were analyzed on a patient as well as on a lesion basis and compared to immunohistochemical staining patterns of CXCR4 and somatostatin receptors SSTR2a and SSTR5. [68Ga]Pentixafor visualized tumor lesions in 6/12 subjects, whereas [18F]FDG revealed sites of disease in 10/12 and [68Ga]DOTATOC in 11/12 patients, respectively. Regarding sensitivity, SSTR-directed PET was the superior imaging modality in all G1 and G2 NET. CXCR4-directed PET was negative in all G1 NET. In contrast, 50% of G2 and 80% of G3 patients exhibited [68Ga]Pentixafor-positive tumor lesions. Whereas CXCR4 seems to play only a limited role in detecting well-differentiated NET, increasing receptor expression could be non-invasively observed with increasing tumor grade. Thus, [68Ga]Pentixafor PET/CT might serve as non-invasive read-out for evaluating the possibility of CXCR4-directed endoradiotherapy in advanced dedifferentiated SSTR-negative tumors.

Werner|Rudolf A|RA|
Weich|Alexander|A|
Higuchi|Takahiro|T|
Schmid|Jan S|JS|
Schirbel|Andreas|A|
Lassmann|Michael|M|
Wild|Vanessa|V|
Rudelius|Martina|M|
Kudlich|Theodor|T|
Herrmann|Ken|K|
Scheurlen|Michael|M|
Buck|Andreas K|AK|
Kropf|Saskia|S|
Wester|Hans-Jürgen|HJ|
Lapa|Constantin|C|

D000072078:Positron Emission Tomography Computed Tomography

chemokine receptor
Neuroendocrine tumor
CXCR4
SSTR
PET/CT
[68Ga]Pentixafor
DOTATOC
PRRT
peptide receptor radionuclide therapy.


High PTPRQ Expression and Its Relationship to Expression of PTPRZ1 and the Presence of KRAS Mutations in Colorectal Cancer Tissues.

Abstract:
BACKGROUND
The risk of sporadic colorectal cancer (CRC) is strongly influenced by Iifestyle, environmental and genetic factors. Protein tyrosine phosphatases belong to a group of enzymes whose role in CRC has not yet been intensively studied. They play an important role in activation/de-activation of many enzymes, influencing cell biology by catalyzing reactions opposing those catalyzed by kinases. Protein tyrosine phosphatase receptor-like type Q (PTPRQ) and protein tyrosine phosphatase receptor-like type Z polypeptide 1 (PTPRZ1) have both been shown to be important in development of many cancer types including CRC.

MATERIALS AND METHODS
The expression level of PTPRQ and PTPRZ1 was determined by real-time polymerase chain reaction in 16 CRC tissues obtained from patients diagnosed with adenocarcinoma coli.

RESULTS
We revealed a high level of PTPRQ expression (p=0.0080), as well as an association between expression levels of PTPRQ and PTPRZ1 (p<0.0001). Moreover PTPRQ expression was higher in tissues presenting with Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation (p=0.0293).

CONCLUSION
We confirmed the contribution of PTPRZ1 and especially PTPRQ in CRC development, supporting the hypothesis that PTPRQ is a candidate oncogene, playing a crucial role in phosphorylation/dephosphorylation signaling pathways.

Laczmanska|Izabela|I|
Karpinski|Pawel|P|
Gil|Justyna|J|
Laczmanski|Lukasz|L|
Bebenek|Marek|M|
Sasiadek|Maria M|MM|

D020022:Genetic Predisposition to Disease

D060888:Real-Time Polymerase Chain Reaction

D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3

D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5

D020133:Reverse Transcriptase Polymerase Chain Reaction

PTPRQ
PTPRZ1
colorectal cancer
Protein tyrosine phosphatase


Activities of employers and OHS services during the developing COVID-19 epidemic in Poland.

Abstract:
Background
The epidemic is affecting the global economy, plunging many industries. The global extent of the epidemic and government controls, restrictions and constraints have led to imbalances in world trade and have put many companies under pressure. The epidemic is a test of individual companies' ability to operate effectively in the new environment. It is up to managers to mitigate its impact on business. The aim of the article is to identify the activities of employers in Poland related to the protection of workers with the developing epidemic COVID-19.

Methods
A survey was carried out among the employees of OHS services employed in enterprises in Poland. The research was conducted in three stages at two-week intervals. The obtained results were subjected to statistical analyses.

Results
In the analysed three periods a total of 588 answers were obtained, which allowed to formulate conclusions. The research showed that in connection with the COVID-19 epidemic, about 30% of the plants updated their occupational risk assessment, about 40% updated their safety instructions, about 90% of the plants equipped their employees with additional personal protective equipment.

Conclusions
The COVID-19 outbreak in Poland resulted in taking additional actions by employers to protect workers. Systematicity (methodicality) of these activities depended mainly on the seniority of the OHS service. As a border internship indicating a different approach to an emergency situation related to the epidemic, 7 years were set.

COVID-19 epidemic
Enterprises
Occupational risk
Health and safety at work
Health and safety service


Diffusion tensor imaging for multilevel assessment of the visual pathway: possibilities for personalized outcome prediction in autoimmune disorders of the central nervous system.

Abstract: The afferent visual pathway represents the most frequently affected white matter pathway in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). Diffusion tensor imaging (DTI) can reveal microstructural or non-overt brain tissue damage and quantify pathological processes. DTI facilitates the reconstruction of major white matter fiber tracts allowing for the assessment of structure-function and damage-dysfunction relationships. In this review, we outline DTI studies investigating the afferent visual pathway in idiopathic optic neuritis (ON), NMOSD, and MS. Since MS damage patterns are believed to depend on multiple factors, i.e., ON (anterior visual pathway damage), inflammatory lesions (posterior visual pathway damage), and global diffuse inflammatory and neurodegenerative processes, comprehensive knowledge on different contributing factors using DTI in vivo may advance our understanding of MS disease pathology. Combination of DTI measures and visual outcome parameters yields the potential to improve routine clinical diagnostic procedures and may further the accuracy of individual prognosis with regard to visual function and personalized disease outcome. However, due to the inherent limitations of DTI acquisition and post-processing techniques and the so far heterogeneous and equivocal data of previous studies, evaluation of the true potential of DTI as a possible biomarker for afferent visual pathway dysfunction is still substantially limited. Further research efforts with larger longitudinal studies and standardized DTI acquisition and post-processing validation criteria are needed to overcome current DTI limitations. DTI evaluation at different levels of the visual pathway has the potential to provide markers for individual damage evaluation in the future. As an imaging biomarker, DTI may support individual outcome prediction during personalized treatment algorithms in MS and other neuroinflammatory diseases, hereby leveraging the concept of predictive, preventive, and personalized medicine in the field of clinical neuroimmunology.

Kuchling|Joseph|J|0000-0002-7981-2073
Brandt|Alexander U|AU|
Paul|Friedemann|F|
Scheel|Michael|M|

Predictive preventive personalized medicine


The Need for Sexuality Education in Pakistan.

Abstract: Sexuality education is an extremely controversial topic in countries like Pakistan where any dialogue regarding sexual practices is considered taboo. Yet, it is a country with a high prevalence of abortions and sexually transmitted illnesses (STIs). Current knowledge about such issues in the general public is also very poor. Hence, it is extremely important to discuss the advantages of having sexual education programs in Pakistan and analyze the current impact of an absence of such programs and public awareness campaigns.

sexuality education
abortions
sexually transmitted illnesses
hiv


Stimulation of contractions in pregnant human myometrium is associated with 5-HT3 receptors.

Abstract:
BACKGROUND
Serotonin (5-HT) is known to play an important role in regulating uterine contractions. However, the specific receptors involved have not been well characterized. We evaluated whether 5-HT3 receptors exist in human myometrium, and their effects on myometrial contractility when stimulated by a 5-HT3 agonist.

METHODS
Four tissue samples taken from patients undergoing hysterectomy (n=2) and elective cesarean delivery (n=2) were used to detect expression of 5-HT3 receptors on the myometrium using western blotting. For isometric tension measurement, another 12 myometrial strips obtained from patients undergoing elective cesarean delivery were randomly divided into a control group (Group CON) and an RS56812 group (Group RG). In increasing doses from 10-7M to 10-4M, RS56812, a 5-HT3 receptor agonist, was used to investigate the contractile effects after bonding to the 5-HT3 receptor, following which the effects of granisetron were assessed. Amplitude, interval and duration of myometrial contractions were recorded.

RESULTS
Proteins with a molecular mass of 55kDa, consistent with 5-HT3 receptors, were detected both on non-pregnant and late-pregnant human uteri. RS56812 increased the contractile amplitude at concentrations of 10-6M, 10-5M and 10-4M, achieving maximum effect at 10-5M. A prolonged contractile interval was detected at the concentration of 10-4M. However, RS56812 showed no significant effect on contraction duration. Granisetron did not reverse the contractile effects induced by RS56812.

CONCLUSION
5-HT3 receptors are expressed on non-pregnant and pregnant uteri. RS56812 enhanced myometrial contractions, but this was not affected by granisetron, the mechanism of which requires further investigation.

Li|H|H|
Diao|M|M|
Ni|J|J|
Li|P|P|
Zhu|Q|Q|
Wan|Y L|YL|
Ma|Y S|YS|
Lin|X M|XM|

Contraction
Myometrium
5-HT3 receptor
RS56812
Granisetron


Accelerated long-term forgetting is not evident in adults with genetic generalized epilepsy irrespective of the paradigm used.

Abstract: Accelerated long-term forgetting (ALF) is a recently discovered memory disorder characterized by intact acquisition and retention over short delays, followed by abnormally fast rates of forgetting. Accelerated long-term forgetting has been repeatedly found in children, but not in adults, with genetic generalized epilepsy (GGE). It is possible that this discrepancy is due to a difference in paradigms used in these studies. The current study aimed to determine whether adults with GGE displayed ALF using two paradigms, one that required complete learning and another one that did not. In addition, we explored the relationships with everyday memory difficulties, working memory, mood, and epilepsy variables. Fourteen adults with GGE were compared with 16 healthy controls on two verbal memory tests: a modified version of the California Verbal Learning Test learned to a criterion of 100% (complete learning) and Logical Memory from the Wechsler Memory Scale (Fourth Edition) presented only once (incomplete learning). Recall was tested at 2 min, 30 min, and 1 week, and recognition at 1 week only. Working memory, everyday memory, and mood were also assessed. We found no evidence of ALF on either of the two verbal memory paradigms on recall or recognition tests although patients displayed significantly poorer working memory. Moreover, patients with GGE reported significantly more memory difficulties in everyday life, and these were associated with greater mood disturbances but not with memory tests scores. Greater number of antiepileptic drugs and epilepsy severity also related to memory scores on some tests. Our study suggests that a difference in paradigms used to investigate ALF in children and adults with GGE is unlikely to explain the differences in findings. The study tentatively raises a hypothesis that developmental factors may play a role in ALF in patients with GGE; children with GGE may grow out of ALF. Nevertheless, this hypothesis would need to be tested in a longitudinal study that would follow patients from childhood to early adulthood.

Beilharz|Jessica Elise|JE|
Thayer|Zoe|Z|
Nikpour|Armin|A|
Lah|Suncica|S|

D000328:Adult
D004829:Epilepsy, Generalized
D005260:Female
D006801:Humans
D008137:Longitudinal Studies
D008297:Male
D008569:Memory Disorders
D008570:Memory, Short-Term
D011939:Mental Recall
D008875:Middle Aged
D009483:Neuropsychological Tests
D021641:Recognition, Psychology
D055815:Young Adult

Accelerated long-term forgetting
Genetic generalized epilepsy
Memory


Brachytherapy: current status and future strategies -- can high dose rate replace low dose rate and external beam radiotherapy?

Abstract: Brachytherapy delivers the most conformal high dose radiotherapy possible to the prostate, using either a low dose rate (LDR) or high dose rate (HDR) technique. It may be used either alone as monotherapy or in combination with external beam radiotherapy (EBRT) as a local boost. Comparative efficacy studies, including one randomised controlled trial, consistently show higher cancer control rates when brachytherapy is used compared with EBRT alone, with even some evidence of improvement in survival. There are now extensive mature data supporting the use of LDR as monotherapy for patients with low-risk and selected intermediate-risk disease, with most series reporting long-term disease control rates of over 90% after high-quality implants. HDR is most commonly combined with EBRT to treat intermediate- and high-risk disease, with disease control rates of over 90% reported. The low alpha/beta ratio of prostate cancer combined and the ability to optimally sculpt dose distribution provides the biological and dosimetric rationale for HDR. HDR enables more consistent implant quality than LDR, with evidence of lower acute and late toxicity. Many dose and fractionation schedules of HDR in combination with EBRT have been investigated, but a single fraction of 10-15 Gy is commonly combined with EBRT to a dose of 40-50 Gy to treat intermediate- and high-risk disease. High disease control rates are also reported with HDR as monotherapy, particularly in patients with low- and intermediate-risk disease. Although older series have delivered four to six fractions of HDR, there is growing evidence to support the delivery of HDR in three or even two fractions. Single-fraction HDR monotherapy is now being investigated and if early data are confirmed with longer follow-up, may well become the treatment of choice for many men with localised prostate cancer.

external beam
LDR
HDR
Comparative efficacy
image guidance
outcomes


Desmopressin improves platelet activity in acute intracerebral hemorrhage.

Abstract:
BACKGROUND AND PURPOSE
Minimizing hematoma growth in high-risk patients is an attractive strategy to improve outcomes after intracerebral hemorrhage. We tested the hypothesis that desmopressin (DDAVP), which improves hemostasis through the release of von Willebrand factor, improves platelet activity after intracerebral hemorrhage.

METHODS
Patients with reduced platelet activity on point-of-care testing alone (5), known aspirin use alone (1), or both (8) received desmopressin 0.4 μg/kg IV. We measured Platelet Function Analyzer-epinephrine (Siemens AG, Germany) and von Willebrand factor antigen from baseline to 1 hour after infusion start and hematoma volume from the diagnostic to a follow-up computed tomographic scan.

RESULTS
We enrolled 14 patients with of mean age 66.8±14.6 years, 11 (85%) of whom were white and 8 (57%) were men. Mean Platelet Function Analyzer-epinephrine results shortened from 192±18 seconds pretreatment to 124±15 seconds (P=0.01) 1 hour later, indicating improved plate activity. von Willebrand factor antigen increased from 242±96% to 289±103% activity (P=0.004), indicating the expected increase in von Willebrand factor. Of 7 (50%) patients who received desmopressin within 12 hours of intracerebral hemorrhage symptom onset, changes in hematoma volume were modest, -0.5 (-1.4 to 8.4) mL and only 2 had hematoma growth. One patient had low blood pressure and another had a new fever within 6 hours of desmopressin administration.

CONCLUSIONS
Intravenous desmopressin was well tolerated and improved platelet activity after acute intracerebral hemorrhage. Larger studies are needed to determine its potential effects on reducing hematoma growth versus platelet transfusion or placebo.

CLINICAL TRIAL REGISTRATION URL
http://www.clinicaltrials.gov. Unique identifier: NCT00961532.

Naidech|Andrew M|AM|
Maas|Matthew B|MB|
Levasseur-Franklin|Kimberly E|KE|
Liotta|Eric M|EM|
Guth|James C|JC|
Berman|Micheal|M|
Rosenow|Joshua M|JM|
Lindholm|Paul F|PF|
Bendok|Bernard R|BR|
Prabhakaran|Shyam|S|
Bernstein|Richard A|RA|
Kwaan|Hau C|HC|

blood platelets
cerebral hemorrhage
deamino arginine vasopressin


The effects of B cell depletion on immune related adverse events associated with immune checkpoint inhibition.

Abstract: This letter describes the potential effect of B cell depletion on immune related adverse events associated with immune checkpoint inhibition. B cell depleting agents such as rituximab reduce B cell to plasma cell differentiation and antibody production. This treatment strategy is used in several immune mediated inflammatory diseases such as rheumatoid arthritis and small vessel vasculitis. The immune related adverse events associated with immune checkpoint inhibition resemble immune mediated inflammatory diseases. Here, we report a lower incidence of hypothyroidism in a trial of combined B cell depletion and immune checkpoint inhibitor treatment compared with studies of immune checkpoint inhibitor monotherapy. This letter aims to increase awareness of the immune related adverse events associated with immune checkpoint inhibition in future clinical trials of immune checkpoint inhibition together with B cell depletion (primarily trials of B cell lymphomas). Hopefully, observations from these clinical trials can guide future treatment strategies to treat or prevent immune related adverse events associated with immune checkpoint inhibition.

B cell depletion
Immune related adverse events
Immune checkpoint inhibition
Immune mediated inflammatory disease
Hypothyroidism


Sociodemographics and their impacts on risk factor awareness and beliefs about cancer and screening: results from a cross-sectional study in Newfoundland and Labrador.

Abstract:
BACKGROUND
Our objective was to examine cancer risk factor awareness and beliefs about cancer treatment, outcomes, and screening, and how these are mediated by sociodemographic variables, among Newfoundland and Labrador residents.

METHODS
Participants aged 35 to 74 were recruited through Facebook advertising, and a self-administered online questionnaire was used to collect data. Descriptive statistics, Spearman rank correlations, and multivariate logistic regression analyses were performed.

RESULTS
Of the 1048 participants who responded and met the inclusion criteria for this study, 1019 were selected for this analysis. Risk factor recognition was generally good, though several risk factors had poor awareness: being over 70 years old (53.4% respondents aware), having a low-fiber diet (65.0%), and drinking more than 1 unit of alcohol per day (62.8%). Our results showed that the participants' awareness of risk factors was significantly associated with higher income level (rs = 0.237, P <  0.001), higher education (rs = 0.231, P <  0.001), living in rural regions (rs = 0.163, P <  0.001), and having a regular healthcare provider (rs = 0.081, P = 0.010). Logistic regression showed that among NL residents in our sample, those with higher income, post-secondary education, those in very good or excellent health, and those with a history of cancer all had higher odds of having more positive beliefs about cancer treatment and outcomes. Those with a history of cancer, and those with very good or excellent health, also had higher odds of having more positive beliefs about cancer screening. Finally, compared to Caucasian/white participants, those who were non-Caucasian/white had lower odds of having more positive beliefs about cancer screening.

CONCLUSION
Among adults in NL, there was poor awareness that low-fiber diets, alcohol, and age are risk factors for cancer. Lower income and education, rural residence, and not having a health care provider were associated with lower risk factor awareness. We also found a few associations between sociodemographic factors and beliefs about cancer treatment and outcomes or screening. We stress that while addressing awareness is necessary, so too is improving social circumstances of disadvantaged groups who lack the resources necessary to adopt healthy behaviours.

Shi|Fuyan|F|
Shaver|Lance Garrett|LG|
Kong|Yujia|Y|
Yi|Yanqing|Y|
Aubrey-Bassler|Kris|K|
Asghari|Shabnam|S|
Etchegary|Holly|H|
Adefemi|Kazeem|K|
Wang|Peizhong Peter|PP|

D007722:Health Knowledge, Attitudes, Practice

Risk factors
Awareness and beliefs
Cancer
Newfoundland and Labrador
Health behaviours


Coronary artery thromboembolism from left appendage mural thrombus- a rare complication from atrial fibrillation.

Abstract: A 54-year-old man with recurrent, persistent atrial fibrillation was found dead unexpectedly. He was reportedly non-compliant with his medications and was not on anti-coagulant therapy. He was found dead in his residence after complaining of abdominal discomfort a day prior to death. Postmortem examination revealed a thromboembolus occluding the left anterior descending coronary artery that originated from a mural thrombus in the left appendage, in addition to kidney infarcts. Although atrial fibrillation-related thromboembolism is often speculated to be a cause of myocardial infarction with non-obstructive coronary arteries, supporting pathological evidence is rare. This case documents radiological, macroscopic and microscopic images of this important complication from atrial fibrillation.

McCarthy|Sinead|S|
Garland|Jack|J|
Wong|Christopher X|CX|
Tse|Rexson|R|0000-0002-1388-9537

Coronary artery
Thromboembolism
Atrial fibrillation
Postmortem
Autopsy