Anxiety symptoms and risk of dementia and mild cognitive impairment in the oldest old women.

Abstract:
OBJECTIVES
Research is limited and findings conflict regarding anxiety as a predictor of future cognitive decline in the oldest old persons. We examined the relationship between levels of and changes in anxiety symptoms, and subsequent dementia and mild cognitive impairment (MCI) in the oldest old women.

METHOD
We conducted secondary analyses of data collected from 1425 community-dwelling women (mean age = 82.8, SD ±3.1 years) followed on average for five years. The Goldberg Anxiety Scale was used to assess anxiety symptoms at baseline, and an expert clinical panel adjudicated dementia and MCI at follow-up. Participants with probable cognitive impairment at baseline were excluded.

RESULTS
At baseline, 190 (13%) women had moderate/severe anxiety symptoms and 403 (28%) had mild anxiety symptoms. Compared with those with no anxiety symptoms at baseline, women with mild anxiety symptoms were more likely to develop dementia at follow-up (multivariable-adjusted odds ratio = 1.66, 95% confidence interval 1.12-2.45). No significant association was observed between anxiety symptoms and MCI.

CONCLUSION
In the oldest old women, our findings suggest that mild anxiety symptoms may predict future risk of dementia, but not MCI. Future studies should explore potential biological mechanisms underlying associations of anxiety with cognitive impairment.

Kassem|Ahmed M|AM|0000-0003-4053-7841
Ganguli|Mary|M|
Yaffe|Kristine|K|
Hanlon|Joseph T|JT|
Lopez|Oscar L|OL|
Wilson|John W|JW|
Ensrud|Kristine|K|
Cauley|Jane A|JA|
|||


Study on Near-Net Forming Technology for Stepped Shaft by Cross-Wedge Rolling Based on Variable Cone Angle Billets.

Abstract: Considering problems about concaves at the stepped shaft ends, this paper established the plastic flow kinetic theories about metal deforming during the cross-wedge rolling (CWR) process. By means of the DEFORM-3D finite element software and the point tracing method, the forming process of stepped shafts and the forming mechanism of concaves at shaft ends were studied. Based on the forming features of stepped shafts, rolling pieces were designed using variable cone angle billets. Single-factor tests were conducted to analyze the influence law of the shape parameters of billet with variable cone angle on end concaves, and rolling experiments were performed for verification. According to the results, during the rolling process of stepped shafts, concaves will come into being in stages, and the increasing tendency of its depth is due to the wave mode, the parameters of cone angle α, the first cone section length n. Furthermore, the total cone section length m has an increasingly weaker influence on the end concaves. Specifically, cone angle α has the most significant influence on the quality of shaft ends, which is about twice the influence of the total cone section length m. The concave depth will decrease at the beginning, and then increase with the increasing of the cone angle α and the first cone section length n, and it will decrease with the increasing of the total cone section length m. Finite element numerical analysis results are perfectly consistent with experimental results, with the error ratio being lower than 5%. The results provide a reliable theoretical basis for effectively disposing of end concave problems during CWR, rationally confirming the shape parameters of billets with a variable cone angle, improving the quality of stepped shaft ends, and realizing the near-net forming process of cross-wedge rolling without a stub bar.

near-net forming
stepped shaft
variable cone angle billets
plastic flow kinetic theories
cross wedge rolling


Mg-Fe layered double hydroxides modified titanium enhanced the adhesion of human gingival fibroblasts through regulation of local pH level.

Abstract: The durability of dental implants is closely related to osseointegration and surrounding soft tissue sealing. Appropriate local pH favors fibroblasts adhesion and contributes to soft tissue sealing. Layered double hydroxides (LDHs) are characterized by adjustable alkalinity, offering a possibility to investigate the influence of pH on cellular behaviors. Herein, we fabricated MgFe LDHs modified titanium. During calcination, the local pH value of LDHs increase, without altering other physics and chemical properties via OH- exchange mechanism. In vitro studies showed that LDHs films calcined at 250 °C for 2 h provide a local pH of 10.17, which promote early adhesion, proliferation, and type I collagen expression of human gingival fibroblasts (hGFs) through the formation of focal adhesion complex and activation of focal adhesion kinase related signaling pathways. In conclusion, endowing the titanium surface with appropriate alkalinity by MgFe LDHs films enhances the adhesion of hGFs, providing a new strategy of designing multifunctional biomaterials for soft tissue sealing around dental implants.

Yin|Yijia|Y| Jian|Linjia|L| Li|Baoe|B| Liang|Chunyong|C| Han|Xianglong|X| Zhao|Xuefeng|X| Wang|Donghui|D|

Layered double hydroxides
Adhesion
Dental implants
Soft tissue sealing
Alkaline microenvironment


The features of AECOPD with carbon dioxide retention.

Abstract:
BACKGROUND
Chronic obstructive pulmonary disease (COPD) with carbon dioxide retention is associated with a worsening clinical condition and the beginning of pulmonary ventilation decompensation. This study aimed to identify the factors associated with carbon dioxide retention.

METHODS
This was a retrospective study of consecutive patients with COPD (meeting the Global Initiative for Chronic Obstructive Lung Disease diagnostic criteria) hospitalized at The Ninth Hospital of Xi'an Affiliated Hospital of Xi'an Jiaotong University between October 2014 and September 2017. The baseline demographic, clinical, laboratory, pulmonary function, and imaging data were compared between the 86 cases with carbon dioxide retention and the 144 cases without carbon dioxide retention.

RESULTS
Compared with the non-carbon dioxide retention group, the group with carbon dioxide retention had a higher number of hospitalizations in the previous 12 months (p = 0.013), higher modified Medical Research Council (mMRC) dyspnea scores (p = 0.034), lower arterial oxygen pressure (p = 0.018), worse pulmonary function (forced expiratory volume in one second/forced vital capacity [FEV1/FVC; p < 0.001], FEV1%pred [p < 0.001], Z5%pred [p = 0.004], R5%pred [p = 0.008], R5-R20 [p = 0.009], X5 [p = 0.022], and Ax [p = 0.011]), more severe lung damage (such as increased lung volume [p = 0.011], more emphysema range [p = 0.007], and lower mean lung density [p = 0.043]). FEV1 < 1 L (odds ratio [OR] = 4.011, 95% confidence interval [CI]: 2.216-7.262) and emphysema index (EI) > 20% (OR = 1.926, 95% CI: 1.080-3.432) were independently associated with carbon dioxide retention in COPD.

CONCLUSION
Compared with the non-carbon dioxide retention group, the group with carbon dioxide retention had different clinical, pulmonary function, and imaging features. FEV1 < 1 L and EI > 20% were independently associated with carbon dioxide retention in AECOPD.

TRIAL REGISTRATION
ChiCTR-OCH-14004904 . Registered 25 June 2014.

D029424:Pulmonary Disease, Chronic Obstructive

Carbon dioxide retention
Chronic obstructive pulmonary disease
Emphysema index
Acute exacerbation
Pulmonary function test


Mining the proliferative diabetic retinopathy-associated genes and pathways by integrated bioinformatic analysis.

Abstract:
PURPOSE
Diabetic retinopathy (DR) especially proliferative diabetic retinopathy (PDR) is a serious eye disease. We aimed to identify key pathway and hub genes associated with PDR by analyzing the expression of retinal fibrovascular tissue in PDR patients.

METHODS
First raw data were downloaded from the Gene Expression Omnibus database. Median normalization was subsequently applied to preprocess. Differentially expressed genes (DEGs) analyzed with the Limma package. Weighted correlation network analysis (WGCNA) was utilized to build the co-expression network for all genes. Then, we compared the DEGs and modules filtered out by WGCNA. A protein-protein interaction network based on the STRING web site and the Cytoscape software was constructed by the overlapping DEGs. Next, the Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed. Finally, we used the Comparative Toxicogenomics Database to identify some important pathways and hub genes tightly related to PDR.

RESULTS
Functional enrichment analysis showed that the pathway of cytokine-cytokine receptor interaction was significantly related to PDR eight hub genes which were associated with pathway including tumor necrosis factor (TNF), tumor necrosis factor receptor superfamily member 12A (TNFRSF12A), C-C chemokine 20 (CCL20), chemokine (C-X-C motif) ligand 2 (CXCL2), oncostatin M (OSM) interleukin 10 (IL10), interleukin 15 (IL 15), and interleukin 1B (IL1B).

CONCLUSIONS
We identified one pathway and eight hub genes, which were associated with PDR. The pathway provided references that will advance the understanding of mechanisms of PDR. Moreover, the hub genes may serve as therapeutic targets for precise diagnosis and treatment of PDR in the future.

Sun|Haiyan|H| Cheng|Yahui|Y| Yan|Zhipeng|Z| Liu|Xiaokun|X| Zhang|Jun|J|

Proliferative diabetic retinopathy
DEGs
WGCNA


Passion for an activity: a new predictor of sleep quality.

Abstract:
STUDY OBJECTIVES
The present research examines the relationship between people's frequent involvement in an activity they like and find important (i.e., a passion) and the quality of their sleep. Research on the dualistic model of passion has widely documented the relationship between individuals' type of passion-harmonious versus obsessive-and the quality of their mental and physical health. However, research has yet to examine the relationship between passion and sleep quality. Building on prior research has shown that obsessive (vs harmonious) passion is related to depressive mood symptoms-an important factor associated with sleep problems-we hypothesized that obsessive passion would be associated with overall worse sleep quality, whereas harmonious passion would predict better sleep quality.

METHODS
A sample of 1,506 Americans filled out an online questionnaire on sleep habits and passion. Sleep quality was measured using the Pittsburgh Sleep Quality Index. Hierarchical linear regressions and mediation analyses were carried out with results confirming our hypotheses.

RESULTS
Obsessive passion for an activity was associated with worse sleep quality, whereas harmonious passion was associated with better sleep quality, adjusting for demographics, the type of passionate activity and its self-reported importance, alcohol and tobacco consumption, BMI, self-reported health, and diagnosed health conditions. The relationship between both types of passion and sleep quality was mediated by depressive mood symptoms.

CONCLUSIONS
Our study presents evidence of a strong relationship between sleep quality and passion, opening the door for future research to create new interventions to improve people's sleep and, consequently, their well-being.

Bélanger|Jocelyn J|JJ|
Raafat|Karima A|KA|
Nisa|Claudia F|CF|
Schumpe|Birga M|BM|

sleep quality
dualistic model of passion
Pittsburgh Sleep Quality Index
activity regulation


Spontaneous Regression of Laryngeal Squamous Cell Carcinoma After Biopsy.

Abstract: Approximately 7 cases of spontaneous regression of adult laryngeal carcinoma have been published in the literature since 1900. This case presents a 62-year-old male with a 6-month history of hoarseness who was subsequently diagnosed with a T1aN0M0 left true vocal fold squamous cell carcinoma (SCC) after biopsy. One month following the initial biopsy, histopathological findings on repeat biopsy revealed absence of malignancy and regression of the tumor without radiation. There has been no evidence of tumor recurrence. This case exemplifies how innate immune modulation may play a role in the spontaneous regression of laryngeal SCC, although the mechanism remains unknown.

spontaneous regression
laryngeal
squamous cell carcinoma
true vocal fold
immune modulation


Parental characteristics and the risk of schizophrenia in a Chinese population: a case-control study.

Abstract:
BACKGROUND
Genetic studies have provided convergent results indicating that schizophrenia is a polygenic disorder with a heritability estimate of ∼60-80%. The propensity for schizophrenia is ∼10 times higher in individuals with first-degree relatives with schizophrenia when compared to the general population.

AIM
To identify associations between parental characteristics and the risk of schizophrenia in a Chinese population.

METHODS
Participants with a diagnosis of schizophrenia were recruited along with healthy controls (HCs) matched for age and gender from Weifang, China. Logistic regression models and generalized linear models were used to explore the associations between parental characteristics with the risk and age at onset of schizophrenia. In total, 414 cases and 639 HCs were recruited for the study.

RESULTS
We observed an inverse association between levels of paternal and maternal education and risk of schizophrenia after controlling for potential confounders (Paternal: OR = 1.525, 95% CI: 1.080-2.153, p = .017; Maternal: OR = 1.984, 95% CI: 1.346-2.924, p = .001). Younger paternal and maternal childbearing age were associated with a higher risk of diagnosis of schizophrenia. We furtherly observed that individuals with earlier age at onset of schizophrenia had fewer siblings (p = .007) and had higher rates of parental marital disharmony (p = .033).

CONCLUSION
Our results indicate that parental years of education and age of childbearing are associated with an increased risk of schizophrenia in a Chinese population. Age of onset of schizophrenia was positively associated with a greater number of siblings and negatively associated with parental marital disharmony.

parental
Schizophrenia
Chinese
case-control study
onset age


The Psychosocial and Somatic Effects of Relocation from Remote Canadian First Nation Communities to Urban Centres on Indigenous Peoples with Chronic Kidney Disease (CKD).

Abstract: Chronic kidney disease, also referred to as end-stage renal disease (ESRD), is a prevalent and chronic condition for which treatment is necessary as a means of survival once affected individuals reach the fifth and final stage of the disease. Dialysis is a form of maintenance treatment that aids with kidney functioning once a normal kidney is damaged. There are two main types of dialysis: hemodialysis (HD) and peritoneal dialysis (PD). Each form of treatment is discussed between the patient and nephrologist and is largely dependent upon the following factors: medical condition, ability to administer treatment, supports, geographical location, access to necessary equipment/supplies, personal wishes, etc. For Indigenous Peoples who reside on remote Canadian First Nation communities, relocation is often recommended due to geographical location and limited access to both health care professionals and necessary equipment/supplies (i.e., quality of water, access to electricity/plumbing, etc.). Consequently, the objective of this paper is to determine the psychosocial and somatic effects for Indigenous Peoples with ESRD if they have to relocate from remote First Nation communities to an urban centre. A review of the literature suggests that relocation to urban centres has negative implications that are worth noting: cultural isolation, alienation from family and friends, somatic issues, psychosocial issues, loss of independence and role adjustment. As a result of relocation, it is evident that the impact is profound in terms of an individuals' mental, emotional, physical and spiritual well-being. Ensuring that adequate social support and education are available to patients and families would aid in alleviating stressors associated with managing chronic kidney disease.

D002170:Canada
D006801:Humans
D000081034:Indigenous Peoples
D007676:Kidney Failure, Chronic
D006435:Renal Dialysis
D051436:Renal Insufficiency, Chronic

relocation
remote
Canadian
urban
indigenous
chronic kidney disease
end-stage renal disease
dialysis
Northern
renal failure
rural


The Ability of Patients to Correctly Identify Their Hospitalist on a Patient Satisfaction Survey and the Impact of This Factor on Hospitalist Scores.

Abstract: Background: Patient evaluations of their physician have been utilized to evaluate physician performance and calculate hospital reimbursement. Despite the routine use of these evaluations, little research has been done to evaluate the accuracy of these evaluations. We assessed patient's ability to correctly identify the hospitalist providing their care and whether identification of the hospitalist affected the cumulative satisfaction scores. Methods: This prospective observational study was conducted at a suburban voluntary hospital. Hospitalists were evaluated anonymously by their patients over a 4-month period on a questionnaire designed to assess patient satisfaction. Results: One hundred fifty-eight patients evaluated 16 hospitalists yielding an average of 9.9 evaluations per hospitalist. Forty Nine (31%) patients were able to identify their hospitalist. The top score (3) accounted for 76% of patient responses across all questions. Significant differences (p = .0007) existed in the distribution of these scores when patients who could identify their hospitalist was compared with those who couldn't. The variables for effective communication and hospitalist introduction were scored significantly higher by patients who could identify their hospitalist (2.77 vs 2.55; p = .027 and 2.90 vs 2.67; p = .005). Patients of younger age and female gender were more likely identify their hospitalist. Conclusions: Less than one-third of patients were able to correctly identify their hospitalist. The variables for effective communication and hospitalist introduction to the patient were scored significantly higher by patients who could identify their hospitalist. The elimination of scores by patients who could not correctly identify their provider resulted in marked changes in the percentile ranking of these providers.

Ryan|Michele C|MC|
Ryan|William J|WJ|
Castro|Gabriela I|GI|
Khlat|Mickel|M|
Ryan|James G|JG|

evaluation
physician
metrics
patient experience


CYP1A1 gene polymorphisms and smoking status as modifier factors for lung cancer risk.

Abstract:
OBJECTIVE
Lung cancer remains the most prevalent malignancy worldwide. Susceptibility to lung cancer has been shown to be modulated by inheritance of polymorphic genes. Several metabolic enzymes are currently under investigation for their possible role in lung cancer susceptibility, including members of the cytochrome P450 (CYP) superfamily. The aim of this work was to identify the correlation between CYP1A1 m1 and m2 polymorphisms and lung cancer risk and figure its interactions with smoking as genetic modifiers in the etiology of lung cancer in the Egyptian population.

MATERIALS AND METHODS
One hundred and ten patients with lung cancer and one hundred and ten controls were enrolled in the study. CYP1A1 m1 and m2 polymorphisms were determined using polymerase chain reaction restriction fragment length polymorphism.

RESULTS
Subjects carrying TC and CC genotypes of CYP1A1 m1 and AG and GG genotypes of CYP1A1 m2 were significantly more likely to develop lung cancer especially squamous cell carcinoma. The proportion of lung cancer attributable to the interaction of smoking and CYP1A1 m1 and CYP1A1 m2 polymorphisms was 32% and 52% respectively.

CONCLUSION
Our results revealed that CYP1A1 m1 and m2 polymorphisms contribute to smoking related lung cancer risk in the Egyptian population.

Hussein|Atef G|AG|
Pasha|Heba F|HF|
El-Shahat|Hanan M|HM|
Gad|Doaa M|DM|
Toam|Mostafa M|MM|

D020022:Genetic Predisposition to Disease

D012150:Polymorphism, Restriction Fragment Length

Polymorphism
Lung cancer
CYP1A1 m1
CYP1A1 m2


Impact of ground- and excited-state aromaticity on cyclopentadiene and silole excitation energies and excited-state polarities.

Abstract: A new qualitative model for estimating the properties of substituted cyclopentadienes and siloles in their lowest ππ* excited states is introduced and confirmed through quantum chemical calculations, and then applied to explain earlier reported experimental excitation energies. According to our model, which is based on excited-state aromaticity and antiaromaticity, siloles and cyclopentadienes are cross-hyperconjugated "aromatic chameleons" that adapt their electronic structures to conform to the various aromaticity rules in different electronic states (Hückel's rule in the π(2) electronic ground state (S0) and Baird's rule in the lowest ππ* excited singlet and triplet states (S1 and T1)). By using pen-and-paper arguments, one can explain polarity changes upon excitation of substituted cyclopentadienes and siloles, and one can tune their lowest excitation energies by combined considerations of ground- and excited-state aromaticity/antiaromaticity effects. Finally, the "aromatic chameleon" model can be extended to other monocyclic compound classes of potential use in organic electronics, thereby providing a unified view of the S0, T1, and S1 states of a range of different cyclic cross-π-conjugated and cross-hyperconjugated compound classes.

Jorner|Kjell|K|
Emanuelsson|Rikard|R|
Dahlstrand|Christian|C|
Tong|Hui|H|
Denisova|Aleksandra V|AV|
Ottosson|Henrik|H|

aromaticity
electronic structure
organic electronics
conjugation
density functional calculations


Effect of polymorphisms in CYP3A4, PPARA, NR1I2, NFKB1, ABCG2 and SLCO1B1 on the pharmacokinetics of lovastatin in healthy Chinese volunteers.

Abstract:
AIM
This study examined whether gene polymorphisms (CYP3A4, ABCG2, SLCO1B1, NR1I2, PPARA and NFKB1) influenced the pharmacokinetics of lovastatin in Chinese healthy subjects.

PATIENTS & METHOD
Plasma concentrations of lovastatin and lovastatin acid were quantified using LC/MS/MS.

RESULTS
PPARA c.208+3819 G allele carriers had approximately twofold higher AUC0-∞ and Cmax of lovastatin than wild-type (PPARA c.208+3819 AA) subjects. After adjustment for the PPARA variants, subjects with the SLCO1B1 521TT genotype had approximately 50% lower AUC0-∞ of lovastatin acid than those with 521TC/CC genotypes, while the AUC0-∞ of lovastatin lactone in NFKB1-94 DD wild-type carriers was twofold higher than in mutant homozygotes carriers.

CONCLUSION
Gene polymorphisms of PPARA, SLCO1B1 and NFKB1 affected the pharmacokinetics of lovastatin.

Zhao|Guilian|G| Liu|Mei|M| Wu|Xiujun|X| Li|Guofei|G| Qiu|Feng|F| Gu|Jingkai|J| Zhao|Limei|L|

D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2

D027381:Liver-Specific Organic Anion Transporter 1


The metabolic syndrome in thyroid disease: A report from Nigeria.

Abstract:
BACKGROUND
The objective of this study was to determine the prevalence of the metabolic syndrome and its components in people with thyroid disorders.

MATERIALS AND METHODS
112 subjects with a history of thyroid disorders were consecutively enrolled for the study. Clinical data were obtained by interviewing the patients and referring to their case folders and prescriptions. The subjects were categorized into three: thyrotoxic, those with hypothyroidism and those with nontoxic goiters, based on clinical parameters and or thyroid function tests. The study subjects were weighed and their anthropometric indices were documented. The laboratory parameters that were analyzed included total cholesterol, high-density and low-density cholesterol and triglyceride. Statistical analysis was performed using Student's t test, one-way analysis of variance (ANOVA) test and chi-square test.

RESULTS
The study subjects were aged between 14 and 76 years, with a mean age of 44.5 years, and the female:male ratio was 97:15. The mean age and anthropometric indices were comparable in subjects with thyrotoxicosis, hypothyroidism and euthyroidism. The overall prevalence of the metabolic syndrome was 28% and the frequency of occurrence of the metabolic syndrome in subjects with thyrotoxicosis, hypothyroidism and nontoxic goiter was 24%, 40% and 42%, respectively. The commonest occurring metabolic syndrome defining criterion was dysglycemia, while hypertension and elevated triglyceride were the least documented of the criteria.

CONCLUSION
Metabolic syndrome occurs in 1 in every 4 persons with thyroid disorders, and as such, routine screening for this cardiovascular risk factor may be of benefit in this group of people, especially in those with hypothyroidism.

Ogbera|Anthonia O|AO|
Kuku|Sonny|S|
Dada|Olusola|O|


The Spirit Is Willing, But the Flesh is Weak: Why Young People Drink More Than Intended on Weekend Nights-An Event-Level Study.

Abstract:
BACKGROUND
Heavy alcohol use is common among young adults on weekend nights and is assumed to be intentional. However, little is known about the extent to which heavy consumption is planned prior to the onset of drinking and what factors contribute to drinking more than intended. This study investigates drinking intentions at the beginning of an evening and individual and situational factors associated with a subsequent consumption over the course of multiple nights.

METHODS
Using a smartphone application, 176 young people aged 16 to 25 (mean age = 19.1; 49% women) completed questionnaires on drinking intentions, consumption, and drinking environments before, during, and after multiple Friday and Saturday nights (n = 757). Multilevel regressions were used to investigate individual-level and night-level factors associated with previous drinking intentions and subsequent deviations from intentions.

RESULTS
Participants intended to consume 2.5 drinks (SD = 2.8) per night yet consumed 3.8 drinks (SD = 3.9) on average. Drinking intentions were higher among those who frequently went out at night and engaged in more frequent predrinking. Participants drank more than intended on 361 nights (47.7%). For both genders, the number of drinks consumed before 8 pm, attending multiple locations, and being with larger groups of friends contributed to higher consumption than intended at the individual and the night levels. Heavier consumption than intended also occurred when drinking away from home for men and when going to nightclubs for women.

CONCLUSIONS
Making young adults aware of the tendency to drink more than intended, particularly when drinking begins early in the evening, moves from location to location, and includes large groups of friends, may be a fruitful prevention target. Structural measures, including responsible beverage service, may also help in preventing excessive drinking at multiple locations.

Young Adults
Deviation From Intentions
Behavioral Intentions
Ecological Momentary Assessment
Heavy Drinking


Gene therapy for chondral and osteochondral regeneration: is the future now?

Abstract: Gene therapy might represent a promising strategy for chondral and osteochondral defects repair by balancing the management of temporary joint mechanical incompetence with altered metabolic and inflammatory homeostasis. This review analysed preclinical and clinical studies on gene therapy for the repair of articular cartilage defects performed over the last 10 years, focussing on expression vectors (non-viral and viral), type of genes delivered and gene therapy procedures (direct or indirect). Plasmids (non-viral expression vectors) and adenovirus (viral vectors) were the most employed vectors in preclinical studies. Genes delivered encoded mainly for growth factors, followed by transcription factors, anti-inflammatory cytokines and, less frequently, by cell signalling proteins, matrix proteins and receptors. Direct injection of the expression vector was used less than indirect injection of cells, with or without scaffolds, transduced with genes of interest and then implanted into the lesion site. Clinical trials (phases I, II or III) on safety, biological activity, efficacy, toxicity or bio-distribution employed adenovirus viral vectors to deliver growth factors or anti-inflammatory cytokines, for the treatment of osteoarthritis or degenerative arthritis, and tumour necrosis factor receptor or interferon for the treatment of inflammatory arthritis.

Bellavia|Daniele|D|0000-0003-3308-9112
Veronesi|F|F|
Carina|V|V|
Costa|V|V|
Raimondi|L|L|
De Luca|A|A|
Alessandro|R|R|
Fini|M|M|
Giavaresi|G|G|

Expression vectors
Gene therapy procedures
Osteoarthritis
Cartilage repair
Regenerative medicine


Racial Disparity in Time to Surgery and Complications for Hip Fracture Patients.

Abstract:
Backgroud
Racial and ethnic disparities in orthopedic surgery may be associated with worse perioperative complications. For patients with hip fractures, studies have shown that early surgery, typically within 24 to 48 hours of admission, may decrease postoperative morbidity and mortality. Our objective was to determine whether race is associated with longer time to surgery from hospital presentation and increased postoperative complications.

Methods
We queried the National Surgical Quality Improvement Program database from 2011 to 2017 for patients (> 65 years) with hip fractures who underwent surgical fixation. Patients were identified using Current Procedural Terminology codes (27235, 27236, 27244, and 27245). Delayed surgery was defined as time to surgery from hospital admission that was greater than 48 hours. Time to surgery was compared between races using analysis of variance. A multivariate logistic regression analysis adjusting for comorbidities, age, sex, and surgery was performed to determine the likelihood of delayed surgery and rate of postoperative complications.

Results
A total of 58,456 patients who underwent surgery for a hip fracture were included in this study. Seventy-two percent were female patients and the median age was 87 years. The median time to surgery across all patients was 24 hours. African Americans had the longest time to surgery (30.4 ± 27.6 hours) compared to Asians (26.5 ± 24.6 hours), whites (25.8 ± 23.4 hours), and other races (22.7 ± 22.0 hours) (p < 0.001). After adjusting for comorbidities, age, sex, and surgery, there was a 43% increase in the odds of delayed surgery among American Africans compared to whites (odds ratio, 1.43; 95% confidence interval, 1.29-1.58; p < 0.001). Despite higher odds of reintubation, pulmonary embolism, renal insufficiency or failure, and cardiac arrest in African Americans, mortality was significantly lower compared to white patients (4.41% vs. 6.02%, p < 0.001). Asian Americans had the lowest mortality rate (3.84%).

Conclusions
A significant disparity in time to surgery and perioperative complications was seen amongst different races with only African Americans having a longer time to surgery than whites. Further study is needed to determine the etiology of this disparity and highlights the need for targeted strategies to help at-risk patient populations.

Nayar|Suresh K|SK|
Marrache|Majd|M|
Ali|Iman|I|
Bressner|Jarred|J|
Raad|Micheal|M|
Shafiq|Babar|B|
Srikumaran|Uma|U|

National surgical quality improvement program


Endoscopic Double Stenting for the Management of Combined Malignant Biliary and Duodenal Obstruction.

Abstract: Periampullary cancers are often diagnosed at advanced stages and can cause both biliary and duodenal obstruction. As these two obstructions reduce patients' performance status and quality of life, appropriate management of the disease is important. Combined malignant biliary and duodenal obstruction is classified according to the location and timing of the duodenal obstruction, which also affect treatment options. Traditionally, surgical bypass (gastrojejunostomy and hepaticojejunostomy) has been performed for the treatment of unresectable periampullary cancer. However, it has recently been substituted by less invasive endoscopic procedures due to its high morbidity and mortality. Thus, endoscopic double stenting (transpapillary stenting and enteral stenting) has become the current standard of care. Limitations of transpapillary stenting include its technical difficulty and the risk of duodenal-biliary reflux. Recently, endoscopic ultrasound-guided procedures have emerged as a novel platform and have been increasingly utilized in the management of biliary and duodenal obstruction. As the prognosis of periampullary cancer has improved due to recent advances in chemotherapy, treatment strategies for biliary and duodenal obstruction are becoming more important. In this article, we review the treatment strategies for combined malignant biliary and duodenal obstruction based on the latest evidence.

double stenting
duodenal obstruction
anti-reflux metal stent
biliary obstruction
lumen-opposing metal stent


An Augmented Pocketome: Detection and Analysis of Small-Molecule Binding Pockets in Proteins of Known 3D Structure.

Abstract: Protein-ligand interactions form the basis of most cellular events. Identifying ligand binding pockets in proteins will greatly facilitate rationalizing and predicting protein function. Ligand binding sites are unknown for many proteins of known three-dimensional (3D) structure, creating a gap in our understanding of protein structure-function relationships. To bridge this gap, we detect pockets in proteins of known 3D structures, using computational techniques. This augmented pocketome (PocketDB) consists of 249,096 pockets, which is about seven times larger than what is currently known. We deduce possible ligand associations for about 46% of the newly identified pockets. The augmented pocketome, when subjected to clustering based on similarities among pockets, yielded 2,161 site types, which are associated with 1,037 ligand types, together providing fold-site-type-ligand-type associations. The PocketDB resource facilitates a structure-based function annotation, delineation of the structural basis of ligand recognition, and provides functional clues for domains of unknown functions, allosteric proteins, and druggable pockets.

Bhagavat|Raghu|R| Sankar|Santhosh|S| Srinivasan|Narayanaswamy|N| Chandra|Nagasuma|N|

D000465:Algorithms
D001665:Binding Sites
D019295:Computational Biology
D030562:Databases, Protein
D008958:Models, Molecular
D011485:Protein Binding
D011487:Protein Conformation
D011506:Proteins

pocketome
protein-ligand interactions
structure-function relationship
allosteric proteins
druggable proteins
ligand and binding
pocket types
structural bioinformatics
structure-based annotation


Molecular and Functional Phenotypes of Human Bone Marrow-Derived Mesenchymal Stromal Cells Depend on Harvesting Techniques.

Abstract: Mesenchymal stromal cells (MSC) harvested in different tissues from the same donor exhibit different phenotypes. Each phenotype is not only characterized by a certain pattern of cell surface markers, but also different cellular functionalities. Only recently were different harvesting and processing techniques found to contribute to this phenomenon as well. This study was therefore set up to investigate proteomic and functional properties of human bone marrow-derived MSCs (hBM-MSC). These were taken from the same tissue and donor site but harvested either as aspirate or bone chip cultures. Both MSC populations were profiled for MSC markers defined by the International Society for Cellular Therapy (ISCT), MSC markers currently under discussion and markers of particular interest. While classic ISCT MSC markers did not show any significant difference between aspirate and outgrowth hBM-MSCs, our additional characterization panel revealed distinct patterns of differentially expressed markers. Furthermore, hBM-MSCs from aspirate cultures demonstrated a significantly higher osteogenic differentiation potential than outgrowth MSCs, which could be confirmed using a transcriptional approach. Our comparison of MSC phenotypes obtained by different harvesting techniques suggests the need of future standardized harvesting, processing and phenotyping procedures in order to gain better comparability in the MSC field.

phenotype
mesenchymal stromal cells
harvesting technique
characterization
differentiation
osteoimmunology


Cognitive performance in dialysis patients - "when is the right time to test?"

Abstract:
BACKGROUND
Cognitive impairment in chronic kidney disease, especially in end stage renal disease, is a public health problem. Nevertheless, the cause of chronic kidney disease still remains unclear. A prevalence of cognitive impairment in patients with end stage renal disease of up to 87% has been found.

METHODS
The study at hand deals with the research on the - potential - effect of timing on cognitive performance when testing cognitive impairment in hemodialysis patients during the dialysis cycle. We tested cognitive performance with a neuropsychological test battery (RBANS, Repeatable Battery for the Assessment of Neuropsychological Status) on two occasions while patients were on dialysis as well as on a dialysis-free day. In addition, all participants were rated using the Geriatric Depression Scale (GDS) and several demographic and clinical variables were recorded in order to investigate their possible influence on cognitive performance. The patients were recruited in three dialysis centers in the central region of Hesse, Germany. Twenty-six participants completed the 3 testings during a period of 6 weeks. The testing was carried out in the dialysis centers.

RESULTS
Looking at the total scale score, patients achieved the best cognitive performance in the RBANS during the first 2 h on dialysis with 81.1 points. When comparing the scores of the three measurement occasions (first 2 h, Timepoint 1 vs. last 2 h, Timepoint 2 vs. dialysis free day, Timepoint 3, however, no significant difference in the total scale score was detected. But patients showed significantly better cognitive performance in language in the first 2 h (p < 0.001) as well as in the last 2 h (p < 0.001) compared with the dialysis-free day.

CONCLUSION
Due to the high prevalence of cognitive impairment, there is an increasing need to assess cognitive function in dialysis patients. Our data show that the time point of testing (first 2 h on hemodialysis vs. last 2 h on hemodialysis vs. Hemodialysis free day) had no influence of cognitive function in hemodialysis patients in routine indications.

Karakizlis|Hristos|H| Thiele|Stefanie|S| Greene|Brandon|B| Hoyer|Joachim|J|

Cognitive performance
Cognitive impairment
Hemodialysis patients
RBANS
Neurocognitive testing


The micro-damage process zone during transverse cortical bone fracture: No ears at crack growth initiation.

Abstract:
OBJECTIVE
Apply high-resolution benchtop micro-computed tomography (micro-CT) to gain greater understanding and knowledge of the formation of the micro-damage process zone formed during traverse fracture of cortical bone.

METHODS
Bovine cortical bone was cut into single edge notch (bending) fracture testing specimens with the crack on the transverse plane and oriented to grow in the circumferential direction. We used a multi-specimen technique and deformed the specimens to various individual secant modulus loss levels (P-values) up to and including maximum load (Pmax). Next, the specimens were infiltrated with a BaSO4 precipitation stain and scanned at 3.57-μm isotropic voxel size using a benchtop high resolution-micro-CT. Measurements of the micro-damage process zone volume, width and height were made. These were compared with the simple Irwin's process zone model and with finite element models. Electron and confocal microscopy confirmed the formation of BaSO4 precipitate in micro-cracks and other porosity, and an interesting novel mechanism similar to tunneling.

RESULTS
Measurable micro-damage was detected at low P values and the volume of the process zone increased according to a second order polynomial trend. Both width and height grew linearly up to Pmax, at which point the process zone cross-section (perpendicular to the plane of the crack) was almost circular on average with a radius of approximately 550µm (approximately one quarter of the unbroken ligament thickness) and corresponding to the shape expected for a biological composite under plane stress conditions.

CONCLUSION
This study reports details of the micro-damage fracture process zone previously unreported for cortical bone. High-resolution micro-CT enables 3D visualization and measurement of the process zone and confirmation that the crack front edge and process zone are affected by microstructure. It is clear that the process zone for the specimens studied grows to be meaningfully large, confirming the need for the J-integral approach and it does not achieve steady state at Pmax in most specimens. With further development, this approach may become valuable towards better understanding the role of the process zone in cortical bone fracture and the effects of relevant modifications towards changes in fracture toughness in a cost effective way.

Willett|Thomas|T|
Josey|David|D|
Lu|Rick Xing Ze|RXZ|
Minhas|Gagan|G|
Montesano|John|J|

Micro-damage
Process zone
Cortical bone
J-integral
Fracture toughness
Micro computed tomography


Assessing the Relationship between Helicobacter pylori and Chronic Kidney Disease.

Abstract: The relationship between Helicobacter pylori infection and/or gastric disorders and chronic kidney disease (CKD) has not been elucidated. We investigated the relationship between Helicobacter pylori and/or atrophic gastritis (AG) and chronic kidney disease. In total, 3560 participants (1127 men and 2433 women) were eligible for this cross-sectional study. We divided participants into four study groups: with/without Helicobacter pylori infection and with/without AG. The HP (+) AG (-) group demonstrated a significant association with CKD compared with the HP (-) AG (-) group (adjusted odds ratio, 1.443; 95% confidence interval, 1.047-1.989). In contrast, the HP (+) AG (+) group showed significantly lower adjusted odds of CKD than the HP (-) AG (-) group (adjusted odds ratio, 0.608; 95% confidence interval, 0.402-0.920). H. pylori infection without AG might be associated with CKD in these participants. Conversely, the HP (+) AG (+) group had lower odds of CKD. Uncovering an association between gastric and renal conditions could lead to development of new treatment strategies.

Hata|Koichi|K| Koyama|Teruhide|T|0000-0002-8161-368X Ozaki|Etsuko|E| Kuriyama|Nagato|N| Mizuno|Shigeto|S| Matsui|Daisuke|D| Watanabe|Isao|I| Uehara|Ritei|R| Watanabe|Yoshiyuki|Y|

Helicobacter pylori
chronic kidney disease
atrophic gastritis
inter-organ interactions


Noise properties and task-based evaluation of diffraction-enhanced imaging.

Abstract: Diffraction-enhanced imaging (DEI) is an emerging x-ray imaging method that simultaneously yields x-ray attenuation and refraction images and holds great promise for soft-tissue imaging. The DEI has been mainly studied using synchrotron sources, but efforts have been made to transition the technology to more practical implementations using conventional x-ray sources. The main technical challenge of this transition lies in the relatively lower x-ray flux obtained from conventional sources, leading to photon-limited data contaminated by Poisson noise. Several issues that must be understood in order to design and optimize DEI imaging systems with respect to noise performance are addressed. Specifically, we: (a) develop equations describing the noise properties of DEI images, (b) derive the conditions under which the DEI algorithm is statistically optimal,

Brankov|Jovan G|JG|
Saiz-Herranz|Alejandro|A|
Wernick|Miles N|MN|

diffraction-enhanced imaging
x-ray
synchrotron
analyzer-based imaging
noise analysis
phase-sensitive imaging


Aspergillus and Rhizopus Fungal Coinfection in a Patient With Multiple Myeloma.

Abstract: Opportunistic fungal infections are rare but life-threatening in immunocompromised patients. We discuss a case of an immunocompromised patient with multiple myeloma who presented with shortness of breath, fever, ocular palsy, and hemiplegia. She was found to have influenza A respiratory tract infection complicated by invasive aspergillosis and mucormycosis. Investigation revealed invasive fungal sinusitis and cerebritis. Serum biomarkers, beta-d-glucan, and galactomannan failed to detect fungal disease. We believe that our case is unique as there is limited data available regarding the occurrence of invasive fungal infections after Influenza infections. Furthermore, it highlights the hurdles in the diagnosis of disseminated fungal infection.

aspergillus
rhizopus
multiple myeloma
influenza a


Distinctive pattern of expression of spermatogenic molecular markers in testes of azoospermic men with non-mosaic Klinefelter syndrome.

Abstract:
PURPOSE
Mature sperm cells can be found in testicular specimens extracted from azoospermic men with non-mosaic Klinefelter syndrome (KS). The present study evaluates the expression of various known molecular markers of spermatogenesis in a population of men with KS and assesses the ability of those markers to predict spermatogenesis.

METHODS
Two groups of men with non-obstructive azoospermia who underwent testicular sperm-retrieval procedures were included in the study: 31 had non-mosaic KS (KS group) and 91 had normal karyotype (NK group). Each group was subdivided into mixed atrophy (containing some mature sperm cells) or Sertoli cell only syndrome according to testicular histology and cytology observations. Semi-quantitative histological morphometric analysis (interstitial hyperplasia and hyalinization, tubules with cells and abnormal thickness of the basement membrane) and expression of spermatogenetic markers (DAZ, RBM, BOLL, and CDY1) were evaluated and compared among those subgroups.

RESULTS
Clear differences in the histological morphometry and spermatogenetic marker expression were noted between the KS and NK groups. There was a significant difference in the expression of spermatogenetic markers between the subgroups of the NK group (as expected), while no difference could be discerned between the two subgroups in the KS group.

CONCLUSION
We conclude that molecular spermatogenetic markers have a pattern of expression in men with KS that is distinctively different from that of men with NK, and that it precludes and limits their use for predicting spermatogenesis in the former. It is suggested that this difference might be due to the specific highly abnormal histological morphometric parameters in KS specimens.

Kleiman|Sandra E|SE|
Yogev|Leah|L|
Lehavi|Ofer|O|
Yavetz|Haim|H|
Hauser|Ron|R|

Klinefelter syndrome
Spermatogenesis
Azoospermia
Infertility
Spermatogenic markers


Multiple sclerosis hospitalizations among users of oral disease-modifying therapies.

Abstract:
BACKGROUND
Oral disease-modifying therapies, namely dimethyl fumarate, fingolimod and teriflunomide, have become standard treatments for multiple sclerosis. Clinical trials demonstrated a reduction in annual relapse rate, but real-world data is lacking, particularly in older adults. The objective of our study is to evaluate the real-world effectiveness of oral disease-modifying therapies among individuals with multiple sclerosis.

METHODS
We used OptumTM ClinformaticsTM Data Mart, a large dataset representative of commercially insured individuals in the United States, to conduct a retrospective cohort study of adult users of three oral disease-modifying therapies from September 2010 through September 2015. The therapies of interest included dimethyl fumarate, teriflunomide, and fingolimod. Hospitalization for multiple sclerosis, an approximation of the clinical trial endpoint for relapse, was the study outcome. Cox proportional hazards models were built to evaluate the association of demographic and clinical factors with multiple sclerosis hospitalization. A subgroup analysis was performed on individuals ages 55 years or older.

RESULTS
We identified 1,823, 318, and 1,156 users of dimethyl fumarate, teriflunomide, and fingolimod that met our inclusion criteria, respectively. Rates of hospitalizations for multiple sclerosis were low among these 3,297 persons (1,041 ages 55+): 36/1,000 patient-years for dimethyl fumarate, 43/1,000 for teriflunomide, and 45/1,000 for fingolimod. Multiple sclerosis hospitalization was associated with therapy switching (adjusted hazard ratio 2.21, 95% confidence interval 1.57-2.84), minority (1.44, 1.10-1.89), and history of relapse in the year preceding oral therapy initiation (5.25, 3.89-7.09).

CONCLUSION
Oral disease-modifying therapies are comparably effective for the outcome of multiple sclerosis hospitalization, even in older adults.

Pham Nguyen|Thanh Phuong|TP|
Jacobs|Dina|D|
Thibault|Dylan|D|
Willis|Allison W|AW|

Multiple sclerosis
Dimethyl fumarate
Teriflunomide
Demyelinating autoimmune disease
Fingolimod hydrochloride
Pharmacoepidemiology


Current status and environment impact of direct straw return in China's cropland - A review.

Abstract: With the development of grain production technologies and improvement of rural living standard, the production and utilization of straw have significantly been changed in China. More than 1 billion tones of straw are produced per year, and vast amount of them are discarded without effective utilization, leading various environmental and social impacts. Straw return is an effective approach of the straw utilization that has been greatly recommended by government and scientists in China. This paper discussed the current status of the straw return in China. Specifically, the production and models of straw return were explored and their environmental impacts were extensively evaluated. It was concluded that straw could be positively effective on the improvement of the soil quality and the grain production. However, it appeared that the straw return also had several neglect negative effects, implying that further research and assessment on the returned straw are required before its large-scale promotion in China.

Li|Hui|H| Dai|Mingwei|M| Dai|Shunli|S| Dong|Xinju|X|


PET imaging reveals sex differences in kappa opioid receptor availability in humans, in vivo.

Abstract: Opioid receptors may play critical roles in alcoholism and other addictions, addiction withdrawal, and depression and are considered pharmacological targets for treatment of these conditions. Sex differences have been demonstrated in mu (MOR) and delta (DOR) opioid receptors in humans, in vivo. In addition, sex differences have been observed in efficacy of treatment targeting kappa opioid receptors (KOR). Our goal in the present study was to compare the availability of KOR (1) between healthy control (HC) men and women. Twenty-seven subjects-18 males (M) and 9 females (F)-underwent PET scans with [(11)C] LY2795050, a selective kappa antagonist tracer. Partial volume correction was applied to all PET data. Volume of distribution (V T) of the tracer was estimated regionally as well as at the voxel level. V T values of males versus females were compared for 19 defined ROIs. Results at the regional and voxel levels were consistent. Males had significantly higher V T and thus a higher KOR availability than women in multiple brain regions. To our knowledge, this is the first report of sex differences in the KOR system in humans, in vivo. These findings could have implications for the treatment of pain with kappa opioid analgesics. The results may also have an impact on the diagnosis and treatment of addictive and other disorders.

Vijay|Aishwarya|A|
Wang|Shuo|S|
Worhunsky|Patrick|P|
Zheng|Ming-Qiang|MQ|
Nabulsi|Nabeel|N|
Ropchan|Jim|J|
Krishnan-Sarin|Suchitra|S|
Huang|Yiyun|Y|
Morris|Evan D|ED|

PET imaging
Sex differences
volume of distribution
kappa opioid receptor system


In vitro fertilization in mice using the MBCD-GSH protocol.

Abstract: Historically, timed mating of either naturally cycling or superovulated females has been the mainstay of pre-implantation embryo production. However, rising cage costs and the rapid expansion of biomedical research programs has necessitated the development of high-throughput approaches to mouse embryo production. In vitro fertilization (IVF) represents one such versatile tool offering many advantages to busy mouse facilities in terms of efficient use of space and resources. For example, strains can be taken off the shelf, frozen quickly as sperm, and recovered at a later date, small colonies can be rapidly expanded to meet demand, and IVF can be used to rescue strains that fail to breed or where the founder male is ill or has died suddenly. This article describes an IVF protocol currently used by many reproductive technologists to assist mouse biology programs.

Guan|Mo|M| Bogani|Debora|D| Marschall|Susan|S| Raspa|Marcello|M| Takeo|Toru|T| Nakagata|Naomi|N| Fray|Martin|M|

mouse IVF cryopreservation methyl-beta-cyclodextrin oocytes spermatozoa


Risk factors associated with nephrolithiasis: a case-control study in China.

Abstract: Nephrolithiasis is a multifactorial disease. The authors conducted a case-control study in China to explore its associated risk factors. A total of 725 nephrolithiasis patients and 553 controls were asked to complete a questionnaire that asked for information about psychological, behavioral, and dietary factors along with a physical and blood biochemical examination. For men, higher education was negatively associated with nephrolithiasis (odds ratio [OR] = 0.6; 95% confidence interval [CI] = 0.4-1.0), whereas hypso-waist-to-hip ratio (hypso-WHR), defined as WHRs >0.9 for men and >0.8 for women (OR = 2.2; 95% CI = 1.4-3.4); overexercise (OR = 2.1; 95% CI = 1.3-3.5); and having experienced negative life events (OR = 2.2; 95% CI = 1.2-4.1) were positively associated with nephrolithiasis. For women, higher fluid intake was negatively associated with nephrolithiasis (OR = 0.6; 95% CI = 0.3-0.9), and abnormal status of blood pressure (BP) and blood lipids was positively associated with nephrolithiasis. Varied factors were related to differences in nephrolithiasis occurrence between genders. Besides taking enough fluids, maintaining a normal metabolic status, avoiding overexercise, and reducing BP might be beneficial in preventing nephrolithiasis.

Zhao|Ai|A|
Dai|Meng|M|
Chen|Yu Juan|YJ|
Chang|Hong En|HE|
Liu|Ai Ping|AP|
Wang|Pei Yu|PY|

nephrolithiasis
case-control study
behaviors
metabolic status
psychological factors


Isolation and molecular detection of Avipoxvirus from field outbreaks in Mymensingh, Bangladesh.

Abstract:
Objective
The present study was performed for isolation, identification, and molecular detection of Avipoxvirus [Turkeypox virus (TPV), Fowlpox virus (FPV), and Pigeonpox virus (PPV)] from field outbreaks in some selected areas of Mymensingh division, Bangladesh.

Materials and Methods
A total of 60 suspected cutaneous nodular samples (10 TPV, 20 PPV, and 30 FPV) were collected. The samples were then subjected to isolation and identification by chicken embryo propagation followed by confirmation using polymerase chain reaction (PCR).

Results
The TPV, FPV, and PPV were successfully isolated and identified from the nodular samples using embryo propagation and PCR technique targeting pox virus p4b gene. Out of 10 Turkeypox suspected field samples, five (50%) were positive for TPV. Similarly, among 30 Fowl pox suspected field samples, 12 (40%), and out of 20 Pigeonpox suspected field samples, eight (40%) were found to be positive for FPV and PPV, respectively. The overall prevalence of avipox (TPV, FPV, and PPV) virus infections in Mymensingh division was 41.67% (n = 25/60).

Conclusion
This study has shown that TPV, FPV, and PPV are circulating in Mymensingh division. The isolated TPV, FPV, and PPV field isolates can be used as vaccine candidates to develop an effective vaccine for effective controlling of the avipox in Mymensingh division and surrounding areas.

Rahman|Saifur|S|
Islam|Md Ariful|MA|
Islam|Md Shafiqul|MS|
Nazir|K H M Nazmul Hussain|KHMNH|
Khan|Md Shahidur Rahman|MSR|

Turkeypox virus
fowlpox virus
pigeonpox virus
PCR


A systematic review on neuromodulation therapies for reducing body weight in patients with obesity.

Abstract: The global prevalence of obesity increases yearly along with a rising demand for efficacious, safe, and accessible treatments. Neuromodulation interventions (i.e., deep brain stimulation [DBS], transcranial magnetic stimulation [TMS], transcranial direct current stimulation [tDCS], percutaneous neurostimulation [PENS], vagus nerve stimulation [VNS], and gastric electrical stimulation [GES]) have been proposed as novel therapies. This systematic review sought to examine the safety and efficacy of neuromodulation therapies in reducing body weight in patients with obesity. Using PRISMA guidelines, we performed a systematic review for studies on neuromodulation for the treatment of obesity, resulting in 60 trials included (7 DBS, 5 TMS, 7 tDCS, 17 PENS and VNS, and 24 GES; a total of 3,042 participants). While promising results have been reported in open label studies, double-blinded randomized clinical trials often did not reach their primary endpoints, with no technique inducing a striking reduction in body weight. Bearing in mind the complexity and multifactorial nature of obesity, it is possible that a single treatment may not be enough for patients to lose or maintain the weight lost at long term.

Gouveia|Flavia Venetucci|FV|
Silk|Esther|E|
Davidson|Benjamin|B|
Pople|Christopher B|CB|
Abrahao|Agessandro|A|
Hamilton|Jill|J|
Ibrahim|George M|GM|
Müller|Daniel J|DJ|
Giacobbe|Peter|P|
Lipsman|Nir|N|
Hamani|Clement|C|0000-0002-7586-2487

D065908:Transcranial Direct Current Stimulation

neuromodulation
obesity
electrical stimulation
weight loss


Effect of the Forth and Fifth Zinc Finger Deletions of MTF-1 on the Expression of Metal Ion Metabolism Related Gene.

Abstract: Metal response element binding transcription factor 1 (MTF-1) is one of the important regulatory proteins involved in the mediation of intracellular metal ion balance, which is zinc dependent. The changes of zinc finger effected its function. MTF-1 mutant 293T cell line was obtained by transferring the vector of MTF-1 4th or 5th mutant zinc finger into 293T cell line that knocked out MTF-1 gene. The results showed that the mutant of 4th zinc finger in MTF-1 protein showed a significant difference on target gene expression compared with 5th zinc finger. Further RNA-seq assay showed that 4th and 5th zinc finger of MTF-1 have a different effect on molecular biological functions, cellular components, and biological process. The mutant of 4th and 5th zinc finger in MTF-1 protein changed different signaling pathways and metal ion metabolism related to genes. The present study evaluated that 4th or 5th mutant zinc finger in MTF-1 gene were associated with the function of MTF-1 protein.

Xu|Hongyan|H| Luo|Ying|Y| Tu|Xinzhuo|X| Cui|Weitong|W| Dou|Ye|Y| Wang|Qinglu|Q|

zinc finger
MTF-1
metal ion metabolism
mutant
ERR signaling


Using the Postoperative Visual Acuity to Monitor the Quality of Cataract Surgery: Does the Day One Visual Acuity following Cataract Surgery Correlate with the Final Visual Acuity?

Abstract:
PURPOSE
Monitoring the visual acuity following cataract surgery is used as a measure of the quality of the surgery in blindness prevention programs in middle- and low-income countries. While the day 1 visual acuity is usually available, the (final) visual acuity after several weeks may not be available, as the majority of patients may not return for review. This study was undertaken to ascertain if the early and late visual acuities are correlated and if the day 1 visual acuity can be used to predict the likely final visual acuity.

METHODS
A retrospective case note review was undertaken of all eyes having cataract surgery over a 6-month period.

RESULTS
There was a positive correlation between the day 1 and week 6 visual acuities in both the World Health Organization categories (Spearman coefficient = 0.4666, P = 0.001) and the logMAR visual acuity scores (Spearman coefficient = 0.5425, P = 0.001).

CONCLUSION
In blindness prevention programs in middle- and low-income countries with poor postoperative follow-up where it is not possible to document the final visual acuity in all the operated cases, there is merit in documenting and monitoring the day 1 visual acuity as a quality control measure.

cataract surgery postoperative visual acuity


Tumor Necrosis Factor Alpha and the Gastrointestinal Epithelium: Implications for the Gut-Brain Axis and Hypertension.

Abstract: The colonic epithelium is the site of production and transport of many vasoactive metabolites and neurotransmitters that can modulate the immune system, affect cellular metabolism, and subsequently regulate blood pressure. As an important interface between the microbiome and its host, the colon can contribute to the development of hypertension. In this critical review, we highlight the role of colonic inflammation and microbial metabolites on the gut brain axis in the pathology of hypertension, with special emphasis on the interaction between tumor necrosis factor α (TNFα) and short chain fatty acid (SCFA) metabolites. Here, we review the current literature and identify novel pathways in the colonic epithelium related to hypertension. A network analysis on transcriptome data previously generated in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats reveals differences in several pathways associated with inflammation involving TNFα (NF-κB and STAT Expression Targets) as well as oxidative stress. We also identify down-regulation of networks associated with gastrointestinal function, cardiovascular function, enteric nervous system function, and cholinergic and adrenergic transmission. The analysis also uncovered transcriptome responses related to glycolysis, butyrate oxidation, and mitochondrial function, in addition to gut neuropeptides that serve as modulators of blood pressure and metabolic function. We present a model for the role of TNFα in regulating bacterial metabolite transport and neuropeptide signaling in the gastrointestinal system, highlighting the complexity of host-microbiota interactions in hypertension.

Hypertension
Blood pressure
Microbiome
Inflammation
Butyrate
Gene networks


Molecular cloning and characterization of CD63 in common carp infected with koi herpesvirus.

Abstract: CD63 is a member of the four-transmembrane-domain protein superfamily and is the first characterized tetraspanin protein. In the present study, we cloned the common carp (Cyprinus Carpio) CD63 (ccCD63) sequence and found that the ccCD63 ORF contained 711 bp and encoded a protein of 236 amino acids. Homology analysis revealed that the complete ccCD63 sequence had 84.08% amino acid similarity to CD63 of Sinocyclocheilus anshuiensis. Subcellular localization analysis revealed that ccCD63 was localized in the cytoplasm. Quantitative real-time PCR (qRT-PCR) analysis indicated that ccCD63 was expressed in the gill, intestine, liver, spleen, brain and kidney, with higher expression in spleen and brain tissues than in the other examined tissues. After koi herpesvirus (KHV) infection, these tissues exhibited various expression levels of ccCD63. The expression level was the lowest in the liver and highest in the brain; the expression level in the brain was 8.7-fold higher than that in the liver. Furthermore, knockdown of ccCD63 promoted KHV infection. Moreover, ccCD63 was correlated with the regulation of RIG-I/MAVS/TRAF3/TBK1/IRF3 and may be involved in the antiviral response through the RIG-I viral recognition signalling pathway in a TRAF3/TBK1-dependent manner. Taken together, our results suggested that ccCD63 upregulated the interaction of KHV with the host immune system and suppressed the dissemination of KHV.

Fan|Z H|ZH|
Xu|Y|Y|
Luo|W|W|
He|X C|XC|
Zheng|T T|TT|
Zhang|J J|JJ|
Xu|X Y|XY|
Qin|Q W|QW|
Lee|X Z|XZ|


Vitamin D deficiency as a risk factor for dementia and Alzheimer's disease: an updated meta-analysis.

Abstract:
BACKGROUND
We aimed to comprehensively explore the associations between serum 25(OH)D deficiency and risk of dementia and Alzheimer's disease(AD).

METHODS
We systematically searched Pubmed, the Cochrane Library, Embase and the reference lists of pertinent review articles for relevant articles published from database inception up until January 2019. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with random effects models using the Stata 12.0 statistical software package.

RESULTS
Twelve prospective cohort studies and four cross-sectional studies were included in this meta-analysis. The pooled HRs of dementia and AD, respectively, were 1.32 (95%CI: 1.16, 1.52) and 1.34 (95%CI: 1.13, 1.60) for vitamin D deficiency (< 20 ng/ml). In the subgroup analyses, the pooled HRs of dementia and AD, respectively, were 1.48 (95%CI: 1.19, 1.85) and 1.51 (95%CI: 1.04, 2.18) for moderate vitamin D deficiency (10-20 ng/ml) and 1.20 (95%CI: 0.99, 1.44) and 1.36 (95%CI: 1.01, 1.84) for severe vitamin D deficiency (< 10 ng/ml).

CONCLUSION
There are significant associations between vitamin D deficiency and both dementia and AD. There are stronger associations between severe vitamin D deficiency (< 10 ng/ml) and both dementia and AD compared to moderate vitamin D deficiency (10-20 ng/ml).

D000465:Algorithms
D000544:Alzheimer Disease
D003430:Cross-Sectional Studies
D016208:Databases, Factual
D003704:Dementia
D006801:Humans
D016016:Proportional Hazards Models
D011446:Prospective Studies
D012307:Risk Factors
D014807:Vitamin D
D014808:Vitamin D Deficiency

Vitamin D deficiency
Dementia
Meta-analysis
Alzheimer’s disease


Defining, Recognizing, and Reporting Malnutrition.

Abstract: Although malnutrition is a common health and social care problem, there is no universal agreement about its definition, prevalence, or method of identification and report. Fifteen definitions of malnutrition were critically examined to assess their variability. They ranged from descriptions of undernutrition alone to under- and overnutrition, with intakes ranging from dietary protein and energy alone to dietary and nondietary sources of all nutrients and energy. Definitions also varied from non-outcome based to those based on functional, physiological, and/or clinical outcomes. Some definitions relied on the pathways by which malnutrition develops, with one apparently requiring loss of fat-free mass. Also examined were nutrition screening tools, diversely developed for detection of malnutrition, management of malnutrition, and prediction of clinical outcomes or health care usage. Their intended use also varied from specific care settings (hospital, community, care homes) to all settings and from specific age groups to all age groups. With all these definitions and tools, there is considerable scope for confusion and misunderstanding. Therefore, to clarify the burden and significance of malnutrition, guidelines for documenting it in routine practice and reporting it in scientific literature are provided.

D019468:Disease Management
D006801:Humans
D044342:Malnutrition
D015596:Nutrition Assessment
D009752:Nutritional Status
D017410:Practice Guidelines as Topic

malnutrition definition identification screening


Gadolinium-Based Nanoparticles for Theranostic MRI-Guided Radiosensitization in Hepatocellular Carcinoma.

Abstract: Background: Radiation therapy (RT) of hepatocellular carcinoma (HCC) is limited by low tolerance of the liver to radiation, whereas radiosensitizers are effective in reducing the required radiation dose. Multimodality gadolinium-based nanoparticles (AGuIX) are small and have enhanced permeability and retention effects; thus, they are very suitable for radiation sensitizer HCC RT. Here, we evaluated the potential value of AGuIX for theranostic MRI-radiosensitization in HCC. Methods: The radiosensitization effects of AGuIX were evaluated via in vitro and in vivo experiments. Tumor growth, apoptosis imaging, and immunohistochemistry were performed to verify the antitumor effects of RT with AGuIX. Results: In vitro evaluation of the efficacy of radiosensitivity of the AGuIX demonstrated that the presence of AGuIX significantly decreased HepG2 cell survival when combined with an X-ray beam. In vivo MRI imaging showed the ratio of tumor/liver concentration of the AGuIX was the highest 1 h after intravenous injection. For antitumor effects, we found that the tumor size decreased by RT-only and RT with AGuIX. The antitumor effects were more effective with high-dose AGuIX-mediated RT. Apoptosis imaging and immunohistochemistry both demonstrated that the degree of the cell apoptosis was highest with a high dose of AGuIX-mediated RT. Conclusions: This study provides compelling data that AGuIX can facilitate theranostic MRI-radiosensitization in HCC.

Hu|Pengcheng|P| Fu|Zhequan|Z| Liu|Guobing|G| Tan|Hui|H| Xiao|Jie|J| Shi|Hongcheng|H| Cheng|Dengfeng|D|

nanoparticles
theranostic
radiosensitization
hepatocellular carcinoma
AGuIX
MRI


Vaginal progesterone to reduce preterm birth among HIV-infected pregnant women in Zambia: a feasibility study protocol.

Abstract:
BACKGROUND
Women infected with HIV have a risk of preterm birth (PTB) that is twice that among uninfected women, and treatment with antiretroviral therapy (ART) may further increase this risk. Progesterone supplementation reduces the risk of preterm delivery in women who have a shortened cervix in the midtrimester. We propose to study the feasibility of a trial of vaginal progesterone (VP) to prevent PTB among HIV-infected women receiving ART in pregnancy. Given low adherence among women self-administering vaginal study product in recent microbicide trials, we plan to investigate whether adequate adherence to VP can be achieved prior to launching a full-scale efficacy trial.

METHODS AND DESIGN
One hundred forty HIV-infected pregnant women in Lusaka, Zambia, will be randomly allocated to daily self-administration of either VP or matched placebo, starting between 20 and 24 gestational weeks. The primary outcome will be adherence, defined as the proportion of participants who achieve at least 80% use of study product, assessed objectively with a validated dye stain assay that confirms vaginal insertion of returned single-use applicators. Secondary outcomes will be study uptake, retention, and preliminary efficacy. We will concurrently perform semi-structured interviews with participants enrolled in the study and with women who decline enrollment to assess the acceptability of VP to prevent PTB and of enrollment to a randomized controlled trial.

DISCUSSION
We hypothesize that VP could prevent PTB among women receiving ART in pregnancy. In preparation for a trial to test this hypothesis, we plan to assess whether participants will be adherent to study product and protocol.

TRIAL REGISTRATION
ClinicalTrial.gov, NCT02970552.

Price|Joan T|JT|
Mollan|Katie R|KR|
Fuseini|Nurain M|NM|
Freeman|Bethany L|BL|
Mulenga|Helen B|HB|
Corbett|Amanda H|AH|
Vwalika|Bellington|B|
Stringer|Jeffrey S A|JSA|

Progesterone
Preterm birth
HIV
Antiretroviral therapy
Sub-Saharan Africa


Presentation and management of symptomatic central bone cement embolization.

Abstract:
BACKGROUND CONTEXT
With more cement augmentation procedures done, the occurrence of serious complications is also expected to rise. Symptomatic central cement embolization is a rare but very serious complication. Moreover, the pathophysiology and treatment of intrathoracic cement embolism remain controversial.

PURPOSE
In this case series, we are trying to identify various presentations and suggest our emergent management scheme for symptomatic central cement embolization.

PATIENT SAMPLE
Retrospective case series of nine patients with symptomatic central cement embolism identified after vertebroplasty with 24 months of follow-up. Level IV.

OUTCOME MEASURES
The degree of dyspnea measured by the New York Heart Association (NYHA) score and/or death related to cement embolism induced cardio/respiratory failure at the final follow-up at 24 months.

METHODS
The nine patients, eight females, and one male had a mean age of 70.25 years (range 65-78 years) and were operated between January 2004 and December 2014. They had percutaneous vertebroplasty for osteoporotic non-traumatic and malignant vertebral collapse of dorsal and lumbar vertebrae. Post-vertebroplasty dyspnea and stitching chest pain were striking in the nine patients. After exclusion of cardiac ischemia and medical pulmonary causes for dyspnea, we identified radiopaque lesions on the chest X-ray. Further echocardiography and high-resolution chest CT were performed for optimal localization. Emergent heart surgery was performed in two patients: interventional therapy was conducted in one patient, while the remaining six patients were conservatively treated by anticoagulation. The management decision was taken in the setting of an interdisciplinary meeting depending on localization, fragmentation, and clinical status.

RESULTS
All patients of this series showed gradual improvement and an uneventful hospital stay. During our 24-month follow-up phase, eight patients showed no subsequent cardiological and/or respiratory symptoms (NYHA I). However, one mortality due to advanced malignancy occurred. Preoperative anemia was the only common intersecting preoperative parameter among these nine patients.

CONCLUSIONS
After cement augmentation, close clinical monitoring is mandatory. A chest CT is pivotal in determining the interdisciplinary management approach in view of the availability of necessary expertise, facilities and the location of the cement emboli whether accessible by cardiac or vascular surgical means. The clinical presentation and its timing may vary and the patient may be seen subsequently by other health care providers obligating a wide-spread awareness for this serious entity among health care providers for this age group as spine surgeons, family and emergency room doctors, and institutional or home-care nurses. Most symptomatic central cement emboli may be treated conservatively.

Open heart and minimally invasive heart surgery

Pulmonary cement emboli and central symptomatic bone embolization


Insects Associated to Crime Scenes in the Northeast of Brazil: Consolidation of Collaboration Between Entomologists and Criminal Investigation Institutes.

Abstract: In Brazil, many studies on Forensic Entomology analyze the activity and succession of flies in animal models. Data on human corpses are always collected and evaluated in isolated cases. This study aimed to list the insect species associated with crime scenes investigated by the Technical-Scientific Institute of criminal expertise of the State of Rio Grande do Norte (ITEP-RN), in the Northeast of Brazil, a region exposed to high homicide rates. In total, 10 cases were investigated, of which 50% were in the initial stage of decomposition. The examined bodies were colonized by species of three orders of insects, Diptera, Coleoptera and Hymenoptera. The order Diptera represented 96% of the total insects, being represented by the following species: Chrysomya albiceps (Wiedemann) (Diptera: Calliphoridae), Chrysomya megacephala (Fabricius) (Diptera: Calliphoridae), Chrysomya putoria (Wiedemann) (Diptera: Calliphoridae), and Cochliomyia macellaria, (Fabricius) (Diptera: Calliphoridae); Musca domestica (Linnaeus) (Diptera: Muscidae); and unidentified females of the Sarcophagidae family. Among beetles, the occurrence of Dermestes maculatus (DeGeer) (Coleoptera: Dermestidae), Necrobia rufipes (De Geer) (Coleoptera: Cleridae), and Onthophagus sp. (Scarabaeidae), as well as unidentified specimens of the families Tenebrionidae and Histeridae were recorded. In addition, specimens of Ectatomma sp. (Formicidae) were also recorded. Considering that the Rio Grande do Norte state presents a high homicide rate and the last cadaver study was conducted over a decade ago, these records update the list of species associated with cadaveric decomposition and contribute to consolidate forensic entomology in the Northeast region.

Meira|L M R|LMR|
Barbosa|T M|TM|
Jales|J T|JT|
Santos|A N|AN|
Gama|R A|RA|

forensic entomology
flies
human corpses
beetles


Sequence assignment for low-resolution modelling of protein crystal structures.

Abstract: The performance of automated model building in crystal structure determination usually decreases with the resolution of the experimental data, and may result in fragmented models and incorrect side-chain assignment. Presented here are new methods for machine-learning-based docking of main-chain fragments to the sequence and for their sequence-independent connection using a dedicated library of protein fragments. The combined use of these new methods noticeably increases sequence coverage and reduces fragmentation of the protein models automatically built with ARP/wARP.

Chojnowski|Grzegorz|G|
Pereira|Joana|J|0000-0002-5588-6588
Lamzin|Victor S|VS|

D000465:Algorithms
D000595:Amino Acid Sequence
D018360:Crystallography, X-Ray
D030562:Databases, Protein
D066264:Datasets as Topic
D000069550:Machine Learning
D062105:Molecular Docking Simulation
D011487:Protein Conformation
D011506:Proteins
D012984:Software

sequence assignment
low-resolution modelling
model building
ARP/wARP
loop building
macromolecular crystallography


Comparison of (18)F-FET and (18)F-FLT small animal PET for the assessment of anti-VEGF treatment response in an orthotopic model of glioblastoma.

Abstract:
BACKGROUND
The radiolabeled amino acid O-(2-(18)F-fluoroethyl)-L-tyrosine (FET) and thymidine analogue 3'-deoxy-3'-(18)F-fluorothymidine (FLT) are widely used for positron emission tomography (PET) brain tumor imaging; however, comparative studies are scarce. The aim of this study therefore was to compare FLT and FET PET for the assessment of anti-VEGF response in glioblastoma xenografts.

METHODS
Xenografts with confirmed intracranial glioblastoma were treated with anti-VEGF therapy (B20-4.1) or saline as control. Weekly bioluminescence imaging (BLI), FLT and FET PET/CT were used to follow treatment response. Tracer uptake of FLT and FET was quantified using maximum standardized uptake (SUVmax) values and tumor-to-background ratios (TBRs). Survival, the Ki67 proliferation index and micro-vessel density (MVD) were evaluated.

RESULTS
In contrast to FLT TBRs, FET TBRs were significantly lower as early as one week after treatment initiation in the anti-VEGF group as compared to the control group. Following two weeks of treatment, both FLT and FET TBRs were significantly lower in the anti-VEGF group. In contrast, no significant difference between the treatment groups was detected using BLI. Furthermore, we found a significantly lower MVD in the anti-VEGF group as compared to the control group. However, we found no difference in the Ki67 proliferation index or mean survival time.

CONCLUSION
FET appears to be a more sensitive tracer than FLT to measure early response to anti-VEGF therapy with PET. Advances in knowledge and implications for patient care FET PET appears to be an early predictor of anti-VEGF efficacy. Confirmation of these results in clinical studies is needed.

Nedergaard|Mette Kjoelhede|MK|
Michaelsen|Signe Regner|SR|
Perryman|Lara|L|
Erler|Janine|J|
Poulsen|Hans Skovgaard|HS|
Stockhausen|Marie-Thérése|MT|
Lassen|Ulrik|U|
Kjaer|Andreas|A|

D042461:Vascular Endothelial Growth Factor A

PET Response Glioblastoma FET FLT Glioma


Detection of cytomegalovirus, herpes virus simplex, and parvovirus b19 in spontaneous abortion placentas.

Abstract:
OBJECTIVE
This study aims to investigate the presence of Cytomegalovirus (CMV), herpes virus simplex (HSV), and parvovirus B19 (PVB19) in the placental tissue of patients who underwent abortions without an otherwise-defined aetiology.

STUDY DESIGN
This cross-sectional study was conducted in a high-risk obstetric maternity facility at a University Hospital in Belo Horizonte, Brazil, from January 2013 to December 2015. We included placenta samples obtained from spontaneous abortions of unknown aetiology. Seventy placenta samples were identified and were classified according to histopathological characteristics. All samples were analysed using immunohistochemistry and polymerase chain reaction for CMV, PVB19, and HSV. The clinical variables were collected from the medical records of patients to verify the association of infection with villitis. The patients were divided into the following groups: I) with villitis (n = 28) and II) without villitis (n = 42).

METHODS
Immunohistochemistry used monoclonal anti-CMV antibody (NCL-CMVpp65, Leica Biosystems, Wetzlar, Germany), anti-PVB19 antibody (NCL-PARVO, Leica Biosystems, Wetzlar, Germany), and anti-HSV1/HSV2 antibodies (NCL-HSV-1 and HSV2, Leica Biosystems, Wetzlar, Germany). The data were analysed using the Statistical Package for Social Sciences (SPSS Inc, Chicago, IL) 19.0.

RESULTS
Viral agents were detected in five patients (7.14%) in the villitis group. Three patients were positive for CMV, one for PVB19, and one for HSV type 2. Foetal and maternal complications were significantly higher in the group with villitis compared with those in the group without villitis (p = .002).

CONCLUSIONS
The prevalence of transplacental viral infections as a cause of spontaneous abortion should be considered high in the placenta with villitis. Thus, this study highlights the need for developing diagnostic tests to clarify the aetiology of abortion and foetal loss.

Aguiar|Regina Amélia Lopes Pessoa de|RALP|

cytomegalovirus
herpes virus simplex
parvovirus B19
spontaneous abortion
vertical transmission


Eculizumab Treatment in a Patient with Hematopoietic Stem Cell Transplantation-Associated Thrombotic Microangiopathy and Steroid-Refractory Acute Graft Versus Host Disease.

Abstract: A 30-year-old man with acquired aplastic anemia underwent an HLA-identical bone marrow transplant. He developed a grade III acute graft versus host disease (GVHD) refractory to various lines of treatment. On post-transplant day 196, he was diagnosed with stem cell transplantation-associated thrombotic micro-angiopathy (HSCT-TMA) and he received treatment with eculizumab 900 mg iv weekly for 4 doses followed by a single dose of 1200 mg 2 weeks later. After the first dose of eculizumab, the patient ceased to require transfusions and a progressive improvement in analytical parameters for microangiopathy was observed until their complete normalization. Coinciding with the improved of HSCT-TMA, the patient presented a clear response to his acute GVHD with disappearance of the diarrhea and bilirubin normalization. He was discharged eight weeks after the start of treatment. Unfortunately, one month later, the patient was readmitted for a GVHD relapse and he died two weeks later by an acute respiratory distress syndrome. In our case, the rapid clinical and analytical response to early treatment with eculizumab supports the implication of the complement in HSCT-TMA and suggests that the drug has a beneficial effect when used as coadjuvant therapy in acute GVHD.

Fernández|Cristina|C| Lario|Ana|A| Forés|Rafael|R| Cabrera|Rafael|R|

Eculizumab
thrombotic microangiopathy
acute graft versus host disease


Laterality interacts with sex across the schizophrenia/bipolarity continuum: an interpretation of meta-analyses of structural MRI.

Abstract: Review of the first comprehensive meta-analysis of VBM (voxel-based morphometry) studies in schizophrenia indicates asymmetrical reductions of anterior cingulate gyrus to the right, and medial temporal lobe (including the uncus) and para-hippocampal gyrus to the left. In subsequent meta-analyses of schizophrenia and bipolar disorder change in these limbic structures is systematically related to change in the insula. Deficits in insula (and para-hippocampal gyrus) to the left, and dorsal anterior cingulate gyrus to the right are greater in schizophrenic psychoses whereas deficits in anterior cingulate to the left and insula to the right are greater in bipolar illness. Thus (1) brain structures implicated in schizophrenia include those implicated in bipolar disorder, (2) the variation that separates the prototypical psychoses may be a subset of that relating to the structural asymmetry (the "torque") characteristic of the human brain, and (3) the meta-analysis of Bora et al. (2012) indicates that laterality of involvement of the insula and cingulate gyrus across the spectrum of bipolar and schizophrenic psychoses is critically dependent upon the sex ratio. Thus structural change underlying the continuum of psychosis relates to the interaction of laterality and sex.

Crow|Timothy J|TJ|
Chance|Steven A|SA|
Priddle|Thomas H|TH|
Radua|Joaquim|J|
James|Anthony C|AC|

Continuum MRI Meta-analysis Torque Language Sapiens Speciation


7-dehydrocholesterol suppresses melanoma cell proliferation and invasion via Akt1/NF-κB signaling.

Abstract: Melanoma is the most lethal cutaneous cancer with a high metastatic rate worldwide, causing ~55,500 deaths annually. Although the selective B-Raf oncogene serine/threonine-kinase (BRAF) inhibitors, dabrafenib and vemurafenib, have been approved for the treatment of BRAF-mutant metastatic melanoma, the 5-year survival rate remains unfavorable due to acquired therapy resistance. Therefore, it is of great importance to develop alternative therapeutic drugs and uncover their mechanisms for the treatment of melanoma. 7-dehydrocholesterol (7-DHC) has been demonstrated to inhibit melanoma, but the mechanism is unclear. Therefore, the present study aimed to elucidate the mechanisms of the inhibitory effect of 7-DHC in melanoma cells via analyzing the proliferation, migration, apoptosis, cell cycle and transcriptional sequencing of melanoma cells treated with 7-DHC, as well as constructing a gene signature according to public data of patients with melanoma. In the present study, 7-DHC, the precursor of vitamin D3, was able to induce apoptosis and inhibit cell proliferation and invasion of melanoma cells in a dose-dependent manner. RNA sequencing of melanoma cells treated with different concentrations of 7-DHC revealed that, compared with untreated melanoma cells, 65 genes were downregulated, and genes involved in the regulation of NF-ĸB import into the nucleus and NF-ĸB signaling were significantly repressed. Consistently, the Akt kinase family was one of most common somatic mutation hotspots in patients with melanoma according to The Cancer Genome Atlas enrichment analysis. Furthermore, 7-DHC decreased the phosphorylation of Akt1-Ser473 rather than that of MEK1, and the decreased phosphorylation of Akt1 subsequently inhibited the translocation of free RELA proto-oncogene NF-κB subunit to the nucleus. Finally, by intersecting downregulated genes by 7-DHC treatment and upregulated genes in patients with melanoma, a 7-DHC gene signature was identified, which was negatively associated with the prognosis. Overall, the present results demonstrated that 7-DHC suppressed melanoma cell proliferation and invasion via the Akt1/NF-ĸB signaling pathway, and 7-DHC key target genes were negatively associated with the prognosis. These findings highlight the potential application of 7-DHC for the treatment of melanoma in the future.

Liu|Jia|J| Zhong|Feiliang|F| Cao|Lei|L| Zhu|Ruiying|R| Qu|Junze|J| Yang|Lin|L| Chen|Tingting|T| Hu|Yunlong|Y| Wang|Ying|Y| Yao|Mingdong|M| Xiao|Wenhai|W| Li|Chun|C| Li|Bo|B| Yuan|Yingjin|Y|


Elicitors and Pre-Fermentative Cold Maceration: Effects on Polyphenol Concentration in Monastrell Grapes and Wines.

Abstract: Vitis vinifera L cv Monastrell is the main red grape variety grown for vinification in the Denomination of Origin Jumilla (southeast Spain). Different strategies are still being tested to optimize available resources both in terms of the environment and to achieve wines with better organoleptic and functional characteristics. The objective of this work was to combine two strategies: the application of methyl jasmonate (MeJ), benzothiadiazole (BTH), and methyl jasmonate + benzothiadiazole (MeJ + BTH) elicitors to Monastrell leaves, and pre-fermentative cold maceration. During two seasons, the experiment was carried out to improve the extraction of the phenolic compounds, whose levels may have increased following the application of elicitors in the field, and to assess the effect of both strategies on the wine quality. Discriminant analysis revealed that independently of the meteorological conditions during both years, the pre-harvest response to the application of elicitors MeJ, BTH, and MeJ + BTH, induced increases in total anthocyanin concentration of the treated grapes, allowing the distinction of the treatments. This analysis also allowed the distinction between the types of maceration used, showing greater extraction of phenolic compounds by the application of low temperature, giving wines with a higher index of total phenols, a greater intensity of color, and a lower luminosity.

methyl jasmonate
benzothiadiazole
phenolic compounds
flavonols


How to compare instrumental variable and conventional regression analyses using negative controls and bias plots.

Abstract: There is increasing interest in the use of instrumental variable analysis to overcome unmeasured confounding in observational pharmacoepidemiological studies. This is partly because instrumental variable analyses are potentially less biased than conventional regression analyses. However, instrumental variable analyses are less precise, and regulators and clinicians find it difficult to interpret conflicting evidence from instrumental variable compared with conventional regression analyses. In this paper, we describe three techniques to assess which approach (instrumental variable versus conventional regression analyses) is least biased. These techniques are negative control outcomes, negative control populations and tests of covariate balance. We illustrate these methods using an analysis of the effects of smoking cessation therapies (varenicline) prescribed in primary care.

Davies|Neil M|NM|
Thomas|Kyla H|KH|
Taylor|Amy E|AE|
Taylor|Gemma M J|GMJ|
Martin|Richard M|RM|
Munafò|Marcus R|MR|
Windmeijer|Frank|F|

Instrumental variables
negative controls
pharmacoepidemiology
causal inference


Patient-accessible tool for shared decision making in cardiovascular primary prevention: balancing longevity benefits against medication disutility.

Abstract:
BACKGROUND
Primary prevention guidelines focus on risk, often assuming negligible aversion to medication, yet most patients discontinue primary prevention statins within 3 years. We quantify real-world distribution of medication disutility and separately calculate the average utilities for a range of risk strata.

METHOD AND RESULTS
We randomly sampled 360 members of the general public in London. Medication aversion was quantified as the gain in lifespan required by each individual to offset the inconvenience (disutility) of taking an idealized daily preventative tablet. In parallel, we constructed tables of expected gain in lifespan (utility) from initiating statin therapy for each age group, sex, and cardiovascular risk profile in the population. This allowed comparison of the widths of the distributions of medication disutility and of group-average expectation of longevity gain. Observed medication disutility ranged from 1 day to >10 years of life being required by subjects (median, 6 months; interquartile range, 1-36 months) to make daily preventative therapy worthwhile. Average expected longevity benefit from statins at ages ≥50 years ranges from 3.6 months (low-risk women) to 24.3 months (high-risk men).

CONCLUSION
We can no longer assume that medication disutility is almost zero. Over one-quarter of subjects had disutility exceeding the group-average longevity gain from statins expected even for the highest-risk (ie, highest-gain) group. Future primary prevention studies might explore medication disutility in larger populations. Patients may differ more in disutility than in prospectively definable utility (which provides only group-average estimates). Consultations could be enriched by assessing disutility and exploring its reasons.

Fontana|Marianna|M|
Asaria|Perviz|P|
Moraldo|Michela|M|
Finegold|Judith|J|
Hassanally|Khalil|K|
Manisty|Charlotte H|CH|
Francis|Darrel P|DP|


Risk factors of metachronous brain metastasis in patients with EGFR-mutated advanced non-small cell lung cancer.

Abstract:
BACKGROUND
NSCLC patients with EGFR mutation were at a higher incidence of developing brain metastasis (BM). Patients with BM are associated with high mortality. Reducing BM incidence becomes increasingly significant for NSCLC patients to achieve prolonged survival. The aim of the study was to explore the possible risk factors of developing metachronous BM during EGFR-TKIs treatment, and to identify the potential candidates for prophylactic cranial irradiation (PCI) or the first-line Osimertinib treatment.

METHODS
A total of 157 consecutive EGFR-mutated advanced NSCLC patients without BM at initial diagnosis in our institution from 2012 and 2018 were retrospectively reviewed. Comparisons of OS were performed based on BM status. The cumulative incidence of metachronous BM was calculated by the Kaplan-Meier method, and the independent risk factors of metachronous BM were investigated by multivariate analysis.

RESULTS
Patients developing metachronous BM had worse survival (mOS: 22.1 months) than patients not-developing BM (mOS: 44.8 months). Moreover, the multivariate analysis indicated that age ≤ 49 years (P = 0.035), number of extracranial metastases (P = 0.013), and malignant pleural effusion (P = 0.002) were independent risk factors of metachronous BM. Furthermore, the 1-year actuarial incidence of developing metachronous BM in patients with no risk factor (n = 101), 1 risk factor (n = 46), and 2 risk factors (n = 10) were 7.01, 14.61, and 43.75%, respectively (P < 0.001).

CONCLUSIONS
Patients developing metachronous BM during EGFR-TKIs treatment have worse outcomes. Our results suggested that EGFR-mutated advanced NSCLC patients with ≥1 risk factors were candidates for PCI or the first-line Osimertinib treatment.

Risk factor
Non-small cell lung cancer
Brain metastases
Epidermal growth factor receptor


The environmental adaptation strategy of seed germination, and roles of the seed pappus on dispersal and hypocotyl hairs on seedling anchorage in Tamarix ramosissima.

Abstract: Seed dispersal, germination and seedling establishment are affected by various ecological factors in desert plant species. Tamarix ramosissima has evolved multiple strategies to facilitate its survival in harsh environments during the early stages of development. In this study, we investigated the effects of different ecological factors on seed germination and seedling growth, the function of the seed pappus in seed dispersal, as well as the function of the hypocotyl hairs in seedling establishment. We found that the seed germination of T. ramosissima was rapid and could occur under a wide range of temperatures (5-30 °C), after long periods of storage (at least 12 months on dispersal), under high concentrations of salts (700-900 mmol·L-1) and polyethylene glycol (PEG) 6000 (500 g·L-1) and under medium concentrations of alkalis (300-500 mmol·L-1). Lower concentrations of salts and PEG promoted seedling growth. The seed pappus had no effect on seed germination, but it might function as an accessory structure that provides a buoyancy force and promotes long-distance seed dispersal. The hypocotyl hairs located on the edge of the hypocotyl end might aid the upright positioning of the seedlings during early development, especially when seed germination occurs under floating or flooding conditions. In conclusion, the germination of T. ramosissima seeds and seedling development can occur under diverse types of abiotic stress, and the seed pappus and hypocotyl hairs played an important role in seed dispersal and seedling establishment.

seed germination
seed pappus
Hypocotyl hairs
Tamarix ramosissima
seed dispersal


Integrated Care for Pregnant Women and Parents With Methamphetamine-Related Mental Disorders.

Abstract: Background: Methamphetamine use is a rapidly increasing cause of morbidity and mortality. Pregnant women and new parents who consume methamphetamine are at high risk since they seldom seek health services despite having multiple needs. We addressed this care gap by implementing an easily accessible program that pools resources from psychiatric, obstetric, and pediatric departments as well as community and government agencies. Method: This real-life observational study evaluated an integrated care program in 27 expecting parents and 57 parents of minors. The outcome criteria were treatment retention, psychosocial functioning, and abstinence. We compared participant demographics according to outcome and applied ordinal logistic regression to predict treatment success. Results: Patients received integrated care for almost 7 months on average. Nearly half achieved stable abstinence and functional recovery. Only one pregnant woman dropped out before a care plan could be implemented, and all women who gave birth during treatment completed it successfully. Three-fourths of patients had psychiatric comorbidities. Patients with depressive disorders were almost 5 times less likely to succeed with treatment. Attention-deficit hyperactivity disorder (ADHD) was diagnosed in nearly 30% of patients who dropped out of a care plan, which was about 4 times more often than in the successful outcome group. Conclusion: Our program engaged pregnant women and parents in treatment and helped them recover from methamphetamine-related mental disorders. Management of comorbid ADHD and depression should be an integral part of care initiatives to counter the methamphetamine crisis that affects parents and children across the globe.

Petzold|Johannes|J|
Spreer|Maik|M|
Krüger|Maria|M|
Sauer|Cathrin|C|
Kirchner|Tobias|T|
Hahn|Susanna|S|
Zimmermann|Ulrich S|US|
Pilhatsch|Maximilian|M|

depression
ADHD
addiction
drug dependence
methamphetamine use disorder
multimodal therapy
outcome prediction
pregnancy