HIV- and hepatitis C-related risk behaviors among people who inject drugs in Uganda: implications for policy and programming.

Abstract:
BACKGROUND
There is a dearth of evidence on injecting drug use and associated HIV and hepatitis C virus (HCV) infections in Uganda. As such, policy and programming for people who inject drugs (PWID) is limited due to scarcity of epidemiological data. We therefore conducted this study to assess the injecting drug and sexual practices among PWID in Kampala Capital City and Mbale Municipality.

METHODS
Using a rapid situation assessment framework, we conducted semi-structured interviews among 125 PWID (102 males and 23 females)-recruited through outreach and snowball sampling. We assessed their injecting drug and sexual practices. We also conducted 12 focus group discussions among PWID and 30 in-depth interviews among key informants.

RESULTS
A total of 125 PWID (81.6% males and 18.4% females) were recruited into the study. Approximately three quarters of PWID started injecting before the age of 25. More females (21.7%) compared to males (13.7%) started injecting by the age of 17. Fifty-seven percent of the PWID in Kampala and 50% in Mbale shared injecting equipment in the last 3 months prior to the study. There was an emerging practice of mixing drugs with blood and sharing it among different PWID as a sign of oneness. Heroin was being injected by 72% of the participants. Less than one half of the PWID had used a condom during the last casual sex, and 42.7% did not use a condom the last time they engaged in sex work. Seventy-six percent of the PWID had undertaken an HIV test in the last 12 months, and 9.2% self-reported to be HIV positive.

CONCLUSIONS
This study highlights the need for introducing harm reduction policies and services including increased access to sterile injecting equipment and education around safer injecting and sexual practices. Programs for PWID should also address the specific needs of female sex workers who inject drugs.

Risk behavior
People who inject drugs
Uganda
Injecting drug use
HIV
Hepatitis C virus
Heroin
Harm reduction
Female sex workers


Ring-like late gadolinium enhancement for predicting ventricular tachyarrhythmias in non-ischaemic dilated cardiomyopathy.

Abstract:
AIMS
Myocardial fibrosis is associated with clinical ventricular tachyarrhythmia (VTA) events in patients with non-ischaemic dilated cardiomyopathy (DCM). Subepicardial or mid-wall ring-like late gadolinium enhancement (LGE) has received increasing attention in recent years. The aim of this study was to investigate the relationship between ring-like LGE and VTAs in DCM.

METHODS AND RESULTS
Patients diagnosed with non-ischaemic DCM who underwent cardiac magnetic resonance with LGE imaging at baseline were investigated. The composite outcome was the occurrence of VTAs defined as sustained ventricular tachycardia, ventricular fibrillation/flutter, aborted sudden cardiac death (SCD), SCD, and appropriate implantable cardioverter-defibrillator intervention. The final cohort comprised 157 patients, including 36 (22.9%) in no LGE group, 48 (30.6%) in focal LGE group, 40 (25.5%) in multi-focal LGE group, and 33 (21%) in ring-like LGE group. Ring-like LGE group patients were younger compared to focal and multi-focal LGE group (P < 0.001) with higher left ventricular ejection fraction (33.0% vs. 24.4% vs. 22.1%, P < 0.001). After a median of 13 ± 7 months follow-up, compared to patients with no LGE, the hazard ratios (HRs) with 95% confidence intervals (CIs) for VTAs were 2.90 (0.56-15.06), 5.55 (1.21-25.44), and 11.75 (2.66-51.92) for patients with focal LGE, multi-focal LGE, and ring-like LGE, respectively. After multivariable adjustment, ring-like LGE group remained associated with increased risk of VTAs (adjusted HR 10.00, 95% CI 1.54-64.98; P = 0.016) independent of the global LGE burden.

CONCLUSION
The ring-like pattern of LGE is independently associated with an increased risk of VTAs in patients with non-ischaemic DCM.

Chen|Wensu|W|0000-0001-9933-8156
Qian|Wen|W|
Zhang|Xinwei|X|
Li|Dongcheng|D|
Qian|Zhiyong|Z|
Xu|Hai|H|
Liao|Shengen|S|
Chen|Xing|X|
Wang|Yao|Y|
Hou|Xiaofeng|X|
Patel|Amit R|AR|
Xu|Yi|Y|
Zou|Jiangang|J|0000-0003-0926-3846

D019028:Magnetic Resonance Imaging, Cine


Use of Bispectrum Analysis to Inspect the Non-Linear Dynamic Characteristics of Beam-Type Structures Containing a Breathing Crack.

Abstract: A breathing crack is a typical form of structural damage attributed to long-term dynamic loads acting on engineering structures. Traditional linear damage identification methods suffer from the loss of valuable information when structural responses are essentially non-linear. To deal with this issue, bispectrum analysis is employed to study the non-linear dynamic characteristics of a beam structure containing a breathing crack, from the perspective of numerical simulation and experimental validation. A finite element model of a cantilever beam is built with contact elements to simulate a breathing crack. The effects of crack depth and location, excitation frequency and magnitude, and measurement noise on the non-linear behavior of the beam are studied systematically. The result demonstrates that bispectral analysis can effectively identify non-linear damage in different states with strong noise immunity. Compared with existing methods, the bispectral non-linear analysis can efficiently extract non-linear features of a breathing crack, and it can overcome the limitations of existing linear damage detection methods used for non-linear damage detection. This study's outcome provides a theoretical basis and a paradigm for damage identification in cracked structures.

Cui|Li|L| Xu|Hao|H| Ge|Jing|J| Cao|Maosen|M| Xu|Yangmin|Y| Xu|Wei|W|0000-0003-3268-3646 Sumarac|Dragoslav|D|

bispectrum
non-linear dynamics
breathing crack
finite element analysis
second harmonic


XB130 Deficiency Causes Congenital Hypothyroidism in Mice due to Disorganized Apical Membrane Structure and Function of Thyrocytes.

Abstract: Congenital hypothyroidism is often caused by genetic mutations that impair thyroid hormone (TH) production, resulting in growth and development defects. XB130 (actin filament associated protein 1 like 2) is an adaptor/scaffold protein that plays important roles in cell proliferation, migration, intracellular signal transduction, and tumorigenesis. It is highly expressed in thyrocytes, however, its function in the thyroid remains largely unexplored.  Xb130 mice and their littermates were studied. Postnatal growth and growth hormone levels were measured, and responses to low or high-iodine diet, and levothyroxine treatment were examined. TH and thyrotropin in the serum and TH in the thyroid glands were quantified. Structure and function of thyrocytes in embryos and postnatal life were studied with histology, immunohistochemistry, immunofluorescence staining, Western blotting, and quantitative reverse transcription polymerase chain reaction.  Xb130 mice exhibited transient growth retardation postnatally, due to congenital hypothyroidism with reduced TH synthesis and secretion, which could be rescued by exogenous thyroxine supplementation. The thyroid glands of Xb130 mice displayed diminished thyroglobulin iodination and release at both embryonic and early postnatal stages. XB130 was found mainly on the apical membrane of thyroid follicles. Thyroid glands of embryonic and postnatal Xb130 mice exhibited disorganized apical membrane structure, delayed folliculogenesis, and abnormal formation of thyroid follicle lumina.  XB130 critically regulates folliculogenesis by maintaining apical membrane structure and function of thyrocytes, and its deficiency leads to congenital hypothyroidism.

Wang|Yingchun|Y|
Shimizu|Hiroki|H|
Xiang|Yun-Yan|YY|
Sugihara|Junichi|J|
Lu|Wei-Yang|WY|
Liao|Xiao-Hui|XH|
Cho|Hae-Ra|HR|
Toba|Hiroaki|H|
Bai|Xiao-Hui|XH|
Asa|Sylvia L|SL|0000-0001-8418-5054
Arvan|Peter|P|0000-0002-4007-8799
Refetoff|Samuel|S|0000-0003-0164-8231
Liu|Mingyao|M|0000-0002-9188-8417

congenital hypothyroidism
folliculogenesis
adaptor protein
cell polarity
thyroglobulin release and iodination
thyroid hormone synthesis and secretion


Sleep-Related Cognitive Processes and the Incidence of Insomnia Over Time: Does Anxiety and Depression Impact the Relationship?

Abstract: Aim: According to the Cognitive Model of Insomnia, engaging in sleep-related cognitive processes may lead to sleep problems over time. The aim was to examine associations between five sleep-related cognitive processes and the incidence of insomnia, and to investigate if baseline anxiety and depression influence the associations. Methods: Two thousand three hundred and thirty-three participants completed surveys on nighttime and daytime symptoms, depression, anxiety, and cognitive processes at baseline and 6 months after the first assessment. Only those without insomnia at baseline were studied. Participants were categorized as having or not having incident insomnia at the next time point. Baseline anxiety and depression were tested as moderators. Results: Three cognitive processes predicted incident insomnia later on. Specifically, more safety behaviors and somatic arousal at Time 1 increased the risk of developing insomnia. When investigating changes in the cognitive processes over time, reporting an increase of worry and safety behaviors also predicted incident insomnia. Depressive symptoms moderated the association between changes in worry and incident insomnia. Conclusion: These findings provide partial support for the hypothesis that cognitive processes are associated with incident insomnia. In particular, safety behaviors, somatic arousal, and worry increase the risk for incident insomnia. Preventative interventions and future research are discussed.

incidence
insomnia
anxiety
depression
safety behaviors
arousal
worry
epidemiology


Parents' knowledge, beliefs, acceptance and uptake of the HPV vaccine in members of The Association of Southeast Asian Nations (ASEAN): A systematic review of quantitative and qualitative studies.

Abstract:
BACKGROUND AND OBJECTIVE
Cervical cancer is the second most common malignancy affecting females in Southeast Asia. Human Papillomavirus (HPV) vaccines have been available since 2006. Several Association of Southeast Asian Nations (ASEAN) member countries have since introduced and/or piloted the HPV vaccine with adolescent females. This systematic review was conducted to understand what factors influence parents' acceptance of the HPV vaccine in the region.

METHODS
Seven databases were searched for qualitative and quantitative studies published up to 16 April 2020. Papers were included if they were peer-reviewed, in English, available in full text, and had a focus on parents' knowledge, beliefs, attitudes and acceptance of the HPV vaccine. Findings were integrated to answer the review question using framework analysis based on the Theory of Planned Behaviour.

RESULTS
Sixteen publications were included and synthesised under the Theory of Planned Behaviour domains: 1) Knowledge, attitudes and acceptance, 2) subjective norms, and 3) perceived behavioural control. Parents' attitudes to HPV vaccination were positive and acceptance to vaccinate their daughters against HPV was high. The uptake was high when the vaccine was offered for free.

CONCLUSION
Parents' acceptance and uptake of the HPV vaccine in ASEAN member-countries was high when the vaccine was offered for free even though their knowledge of cervical cancer and HPV was poor. Further research is needed to see how uptake and acceptance can be maintain when the vaccine is not offered for free.

Wijayanti|Kurnia Eka|KE|
Schütze|Heike|H|
MacPhail|Catherine|C|
Braunack-Mayer|Annette|A|

D007722:Health Knowledge, Attitudes, Practice

D010342:Patient Acceptance of Health Care

Beliefs
Acceptance
Uptake
HPV vaccination
ASEAN
Systematic review
Cervical cancer
Parent knowledge


The involvement of insulin/ToR signaling pathway in reproductive performance of Rhodnius prolixus.

Abstract: Insulins are peptide hormones widely studied for their important regulatory roles in metabolism, growth and development. In insects, insulin signaling along with the target of rapamycin (ToR) are involved in detecting and interpreting nutrient levels. Recently, by transcriptome analysis we reported an up-regulation of transcripts involved in insulin/ToR signaling in unfed Rhodnius prolixus; however, this signaling pathway is only activated in fed insects. Here, continuing with the blood-gorging triatomine R. prolixus as a model, we report the direct effect of insulin/ToR signaling on reproductive performance. By immunofluorescence we identified cells in the brain with positive signal to the R. prolixus ILP (Rhopr-ILP1) and show that the insulin receptor and protein effectors downstream of insulin/ToR signaling activation, are differentially expressed in ovarian follicles dependent on their developmental stage. Using qPCR we find that the expression of transcripts involved in insulin signaling in the central nervous system (CNS), fat body and ovaries increase as the state of starvation progresses, promoting a more highly sensitized state to respond rapidly to ILP/IGF levels. In addition, using dsRNA injection and in vivo and ex vivo assays to promote signaling activation we demonstrate a direct participation of insulin/ToR signaling in coordinating the synthesis of the main yolk protein precursor, vitellogenin, thereby influencing the numbers of eggs laid per female. We thereby show a mechanism by which nutritional signaling regulates reproductive performance in a vector of Chagas disease. As reproduction is responsible for propagation of insect populations, this work is important for the development of innovative biocontrol methods.

Leyria|Jimena|J|
Orchard|Ian|I|
Lange|Angela B|AB|

Insulin/ToR signaling
Reproduction
Insect
Vitellogenin
Nutritional states
Triatominae


Bone morphogenetic protein 7 is associated with the nodal invasion of colon cancer.

Abstract: Environmental and genetic factors interact in the process and treatment of colon cancer, although the underlying mechanisms remain elusive. The aim of the study was to examine the role of whether bone morphogenetic protein 7 (BMP7) is involved in the progression of colon cancer under local intratumoral infiltration lymphocytes. A total of 46 cases of pathologically confirmed specimens were obtained from patients with nodal invasion of colon cancer. The patients were subdivided into three groups based on the nodal invasion stages (N0, N1 and N2). Eleven cases without nodal invasion of colon cancer served as the control group (N0). The phenotype of CD45+, CD4+, CD8+, CD25+ and CD56+ cells and the expression of BMP7 were confirmed by immunofluorescence. The association between BMP7 expression and CD45+/CD4+CD25+/CD8+ cells infiltration was analyzed. The density of CD4+CD25+ T cells within the tumor was associated with nodal invasion in patients with colon cancer. More importantly, the expression of BMP7 was observed in the majority of the cancer tissues. The co-expression pattern of BMP7 in colon cancer cells and intratumor CD4+CD25+ T cells was associated with nodal invasion of colon cancer. In conclusion, the results have shown that the co-expression of BMP7 is inversely associated with the infiltration of CD4+CD25+ T cells of colon cancer. The results suggest the combination of adaptive immunotherapy and biological drugs impact the treatment strategy for colon cancer in distinct clinical settings.

Zhang|Tianqi|T| Fu|Jining|J| Li|Yueting|Y| Wang|Yaohui|Y| Zhang|Long|L| Liu|Ying|Y|

bone morphogenetic protein 7
nodal invasion
colon cancer
CD4+CD25+ T cells


Role of the Primary Cilia on the Macula Densa and Thick Ascending Limbs in Regulation of Sodium Excretion and Hemodynamics.

Abstract: We investigated the significance of the primary cilia on the macula densa and thick ascending limb (TAL) in regulation of renal hemodynamics, sodium excretion, and blood pressure in this study. A tissue-specific primary cilia knock-out (KO) mouse line was generated by crossing NKCC2-Cre mice with IFT88-Δ/flox mice (NKCC2CRE; IFT88Δ/flox), in which the primary cilia were deleted from the macula densa and TAL. NO generation was measured with a fluorescent dye (4,5-diaminofluorescein diacetate) in isolated perfused juxtaglomerular apparatus. Deletion of the cilia reduced NO production by 56% and 42% in the macula densa and TAL, respectively. NO generation by the macula densa was inhibited by both a nonselective and a selective nitric oxide synthesis inhibitors, whereas TAL-produced NO was inhibited by a nonselective and not by a selective NO synthesis 1 inhibitor. The tubuloglomerular feedback response was enhanced in the KO mice both in vitro measured with isolated perfused juxtaglomerular apparatuses and in vivo measured with micropuncture. In response to an acute volume expansion, the KO mice exhibited limited glomerular filtration rate elevation and impaired sodium excretion compared with the wild-type mice. The mean arterial pressure measured with telemetry was the same for wild-type and KO mice fed a normal salt diet. After a high salt diet, the mean arterial pressure increased by 17.4±1.6 mm Hg in the KO mice. On the basis of these findings, we concluded that the primary cilia on the macula densa and TAL play an essential role in the control of sodium excretion and blood pressure.

Song|Jiangping|J|
Wang|Lei|L|
Fan|Fan|F|
Wei|Jin|J|
Zhang|Jie|J|
Lu|Yan|Y|
Fu|Yiling|Y|
Wang|Shaohui|S|
Juncos|Luis A|LA|
Liu|Ruisheng|R|

D000818:Animals
D001794:Blood Pressure
D002923:Cilia
D025461:Feedback, Physiological
D005919:Glomerular Filtration Rate
D006439:Hemodynamics
D007606:Juxtaglomerular Apparatus
D007678:Kidney Glomerulus
D007684:Kidney Tubules
D051379:Mice
D023421:Models, Animal
D009569:Nitric Oxide
D065667:Renal Elimination
D012965:Sodium Chloride


Quantitative Label-Free Proteomic Analysis of Milk Fat Globule Membrane in Donkey and Human Milk.

Abstract: Previous studies have found donkey milk (DM) has the similar compositions with human milk (HM) and could be used as a potential hypoallergenic replacement diet for babies suffering from cow's milk allergy. Milk fat globule membrane (MFGM) proteins are involved in many biological functions, behaving as important indicators of the nutritional quality of milk. In this study, we used label-free proteomics to quantify the differentially expressed MFGM proteins (DEP) between DM (in 4-5 months of lactation) and HM (in 6-8 months of lactation). In total, 293 DEP were found in these two groups. Gene Ontology (GO) enrichment analysis revealed that the majority of DEP participated in regulation of immune system process, membrane invagination and lymphocyte activation. Several significant Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were determined for the DEP, such as lysosome, galactose metabolism and peroxisome proliferator-activated receptor (PPAR) signaling pathway. Our study may provide valuable information in the composition of MFGM proteins in DM and HM, and expand our knowledge of different biological functions between DM and HM.

Zhang|Xinhao|X| Jiang|Bo|B| Ji|Chuanliang|C| Li|Haijing|H| Yang|Li|L| Jiang|Guimiao|G| Wang|Yantao|Y| Liu|Guangyuan|G| Liu|Guiqin|G| Min|Lingjiang|L| Zhao|Fuwei|F|

milk fat globule membrane
donkey
human
comparison
quantitative proteomic


Genetic Analysis of Chelonid Herpesvirus 5 in Marine Turtles from Baja California Peninsula.

Abstract: The Chelonid herpesvirus 5 (ChHV5) is the primary etiological agent associated with fibropapillomatosis (FP), a neoplastic disease in marine turtles. In this study, we report for the first time ChHV5 in marine turtles and a leech from Baja California Peninsula. Eighty-seven black, olive or loggerhead turtle species, one FP tumor and five leeches were analyzed. The tumor sample from an olive, a skin sample from a black and a leech resulted positive of ChHV5 for conventional PCR. Two viral variants were identified and grouped within the Eastern Pacific phylogenetic group, suggesting a possible flow of the virus in this region.

Espinoza|Joelly|J|
Hernández|Elsa|E|
Lara-Uc|María Mónica|MM|
Reséndiz|Eduardo|E|
Alfaro-Núñez|Alonzo|A|
Hori-Oshima|Sawako|S|
Medina-Basulto|Gerardo|G|

Chelonid herpesvirus 5
Marine turtles
Fibropapillomatosis
Eastern Pacific
PCR identification
Phylogenetic analysis


Surgery for Colorectal Cancer: A Trigger for Liver Metastases Development? New Insights into the Underlying Mechanisms.

Abstract: Surgery is a crucial intervention and provides the best chance of cure for patients with colorectal cancer. Experimental and clinical evidence, however, suggests that paradoxically surgery itself may precipitate or accelerate tumor recurrence and/or liver metastasis development. This review addresses the various aspects of surgery-induced metastasis formation and sheds light on the role of inflammation as potential trigger for metastasis development. Understanding these mechanisms may provide potential new perioperative interventions to improve treatment outcomes, and as such could transform the perioperative timeframe from a facilitator of metastatic progression to a window of opportunity to reduce the risk of liver metastasis development. Ultimately, this can potentially improve long-term survival rates and quality of life in patients with colorectal cancer.

Grewal|Simran|S|
Oosterling|Steven J|SJ|
van Egmond|Marjolein|M|

colorectal cancer
liver metastases
treatment
immunology


Assessing the test-retest reliability and smallest detectable change of the Haemophilia Activities List.

Abstract:
INTRODUCTION
The Haemophilia Activities List (HAL) is a preferred instrument to measure self-reported limitations in activities in persons with haemophilia (PWH). Information on reliability and interpretability of HAL scores is lacking.

AIM
To examine the test-retest reliability and smallest detectable change (SDC) of the HAL in adult PWH.

METHODS
Fifty adult (≥18 years) persons with mild to severe haemophilia completed the HAL (42 items, 7 domains, optimum 100) at baseline (T0) and 3-4 weeks later (T1). The intraclass correlation coefficient (ICC) and SDC were calculated for sum and component scores.

RESULTS
Fifty persons with haemophilia were included (median age 49 years; 92% haemophilia A; 70% severe haemophilia). The median (interquartile ranges) HAL sum score was 77 (62 to 99) at T0 and 81 (64 to 98) at T1. Reliability was good with ICCs for sum and component scores >0.9. The SDC for the sum score was 10.2, for the upper extremity component score 9.2, for the basic lower extremity component score 16.7 and for the complex lower extremity component score 13.4.

CONCLUSION
The HAL has a good reliability for the sum and component scores. Score changes of the normalized sum HAL score greater than the SDC 10.2 indicate that the change was not a result of measurement error.

D000328:Adult
D006467:Hemophilia A
D006801:Humans
D007231:Infant, Newborn
D015203:Reproducibility of Results
D057566:Self Report
D011795:Surveys and Questionnaires

reliability
haemophilia
activities
participation
patient-reported outcome
questionnaire


A Comparison between Video and Still Imagery as a Methodology to Determine Southern Hairy-Nosed Wombat (Lasiorhinus latifrons) Burrow Occupancy Rates.

Abstract: Broad-scale abundance estimates of the southern hairy-nosed wombat population use a proxy measure based on counting the number of active burrows, which is multiplied by an index of 'wombats/active burrow'. However, the extant indices were calculated in the 1980s, prior to the use of calicivirus to control rabbits, and used invasive monitoring methods which may have affected the results. We hypothesise that the use of video might provide a logistically simple, non-invasive means of calculating updated indices. To this end, motion-activated, infra-red still and video cameras were placed at various distances outside active wombat burrows in the South Australian Murraylands and Eyre Peninsula regions. The captured imagery was inspected to determine how often the burrow was occupied by one or more wombats, and how effective the cameras were at detecting wombat activity. Video data was clearly superior to the still imagery, with more than twice as many burrow occupancies being positively identified (still: 43%). The indices of wombats/active burrow calculated based on video imagery were: Murraylands: 0.43, Eyre Peninsula: 0.42. 1948 false positive videos were recorded, of which 1674 (86%) occurred between noon and sunset.

wombats
species abundance
warrens
wildlife cameras


Oil Motion Control by an Extra Pinning Structure in Electro-Fluidic Display.

Abstract: Oil motion control is the key for the optical performance of electro-fluidic displays (EFD). In this paper, we introduced an extra pinning structure (EPS) into the EFD pixel to control the oil motion inside for the first time. The pinning structure canbe fabricated together with the pixel wall by a one-step lithography process. The effect of the relative location of the EPS in pixels on the oil motion was studied by a series of optoelectronic measurements. EPS showed good control of oil rupture position. The properly located EPS effectively guided the oil contraction direction, significantly accelerated switching on process, and suppressed oil overflow, without declining in aperture ratio. An asymmetrically designed EPS off the diagonal is recommended. This study provides a novel and facile way for oil motion control within an EFD pixel in both direction and timescale.

Dou|Yingying|Y| Tang|Biao|B| Groenewold|Jan|J| Li|Fahong|F| Yue|Qiao|Q| Zhou|Rui|R| Li|Hui|H| Shui|Lingling|L| Henzen|Alex|A| Zhou|Guofu|G|

oil motion
electro-fluidic displays
extra pinning structure (EPS)
response time


Gastrointestinal tuberculosis following renal transplantation accompanied with septic shock and acute respiratory distress syndrome: a survival case presentation.

Abstract:
BACKGROUND
Post-transplant tuberculosis (PTTB) is a serious opportunistic infection in renal graft recipients with a 30-70 fold higher incidence compared to the general population. PTTB occurs most frequently within the first years after transplantation, manifesting as pulmonary or disseminated TB. Gastrointestinal TB (GITB) is a rare and potentially lethal manifestation of PTTB and may show delayed onset in renal transplant recipients due to the use of lower doses of immunosuppressants. Further, non-specificity of symptoms and the common occurrence of GI disorders in transplant recipients may delay diagnosis of GITB.

CASE PRESENTATION
Here we report a rare survival case of isolated GITB in a renal transplant recipient, occurring seven years after transplantation. The patient's condition was complicated by severe sepsis with positive blood culture Staphylococcus haemolyticus, septic shock, multiple organ failure including acute respiratory distress syndrome (ARDS) and acute renal failure, requiring mechanical ventilation, vasopressor circulatory support and intermittent hemodialysis. Furthermore, nosocomial infections such as invasive aspergillosis and Pseudomonas aeruginosa occurred during hospitalization. Antituberculosis therapy (rifampicin, isoniazid, ethambutol and pyrazinamide) was initiated upon Mycobacterium confirmation. Moreover, treatment with voriconazole due to the Aspergillus flavus and meropenem due to the Pseudomonas aeruginosa was initiated, the former necessitating discontinuation of rifampicin. After 34 days, the patient was weaned from mechanical ventilation and was discharged to the pulmonary ward, followed by complete recovery.

CONCLUSION
This case offers a guideline for the clinical management towards survival of GITB in transplant patients, complicated by septic shock and multiple organ failure, including acute renal injury and ARDS.

Cikova|Andrea|A|
Vavrincova-Yaghi|Diana|D|
Vavrinec|Peter|P|
Dobisova|Anna|A|
Gebhardtova|Andrea|A|
Flassikova|Zora|Z|
Seelen|Mark A|MA|
Henning|Robert H|RH|
Yaghi|Aktham|A|

D003428:Cross Infection
D005260:Female
D006801:Humans
D016030:Kidney Transplantation
D008875:Middle Aged
D009102:Multiple Organ Failure
D009894:Opportunistic Infections
D011183:Postoperative Complications
D012128:Respiratory Distress Syndrome
D012772:Shock, Septic
D013997:Time Factors
D016896:Treatment Outcome
D014385:Tuberculosis, Gastrointestinal

Gastrointestinal tuberculosis
Renal transplantation
Septic shock
Acute respiratory distress syndrome
Multiple organ failure


Heterocyst Development and Diazotrophic Growth of Anabaena variabilis under Different Nitrogen Availability.

Abstract: Nitrogen is globally limiting primary production in the ocean, but some species of cyanobacteria can carry out nitrogen (N) fixation using specialized cells known as heterocysts. However, the effect of N sources and their availability on heterocyst development is not yet fully understood. This study aimed to evaluate the effect of various inorganic N sources on the heterocyst development and cellular growth in an N-fixing cyanobacterium, Anabaena variabilis. Growth rate, heterocyst development, and cellular N content of the cyanobacteria were examined under varying nitrate and ammonium concentrations. A. variabilis exhibited high growth rate both in the presence and absence of N sources regardless of their concentration. Ammonium was the primary source of N in A. variabilis. Even the highest concentrations of both nitrate (1.5 g L-1 as NaNO3) and ammonium (0.006 g L-1 as Fe-NH4-citrate) did not exhibit an inhibitory effect on heterocyst development. Heterocyst production positively correlated with the cell N quota and negatively correlated with vegetative cell growth, indicating that both of the processes were interdependent. Taken together, N deprivation triggers heterocyst production for N fixation. This study outlines the difference in heterocyst development and growth in A. variabilis under different N sources.

heterocyst
diazotrophic growth
nitrogen availability
Anabaena variabilis
cell quota
nitrogen-fixation


Imaging of extracellular cathepsin S activity by a selective near infrared fluorescence substrate-based probe.

Abstract: We designed a near-infrared fluorescent substrate-based probe (SBP), termed MG101, for monitoring extracellular cathepsin S (CatS) activity. We conceived a fused peptide hairpin loop-structure, combining a CatS recognition domain, an electrostatic zipper (with complementary charges of a polyanionic (D-Glu)5 segment and a polycationic (D-Arg)5 motif, as well as a N and C terminal Förster resonance energy transfer pair (donor: AlexaFluor680; quencher: BHQ3) to facilitate activity-dependent imaging. MG101 showed excellent stability since no fluorescence release corresponding to a self-dequenching was observed in the presence of either 2 M NaCl or after incubation at a broad range of pH (2.2-8.2). Cathepsins B, D, G, H, and K, neutrophil elastase and proteinase 3 did not cleave MG101, while CatS, and to a lesser extent CatL, hydrolysed MG101 at pH 5.5. However MG101 was fully selective for CatS at pH 7.4 (kcat/Km = 140,000 M-1 s-1) and sensitive to low concentration of CatS (<1 nM). The selectivity of MG101 was successfully endorsed ex vivo, as it was hydrolysed in cell lysates derived from wild-type but not knockout CatS murine spleen. Furthermore, application of the SBP probe with confocal microscopy confirmed the secretion of active CatS from THP-1 macrophages, which could be abrogated by pharmacological CatS inhibitors. Taken together, present data highlight MG101 as a novel near-infrared fluorescent SBP for the visualization of extracellular active CatS from macrophages and other cell types.

Wartenberg|Mylène|M|
Saidi|Ahlame|A|
Galibert|Mathieu|M|
Joulin-Giet|Alix|A|
Burlaud-Gaillard|Julien|J|
Lecaille|Fabien|F|
Scott|Christopher J|CJ|
Aucagne|Vincent|V|
Delmas|Agnès F|AF|
Lalmanach|Gilles|G|

D031541:Fluorescence Resonance Energy Transfer

Förster resonance energy transfer (FRET)


Expression of multiple formins in adult tissues and during developmental stages of mouse brain.

Abstract: Formins are highly conserved heterogeneous family of proteins with several isoforms having significant contribution in multiple cellular functions. Formins play crucial role in remodelling of actin cytoskeleton and thus play important role in cell motility. Formins are also involved in many cellular activities like determining cell polarity, cytokinesis and morphogenesis. Formins are multi domain protein with characteristic homodimeric formin homology 2 (FH2) domain. It nucleates the actin filaments and its activity is regulated by the presence of characteristic formin homology 1 (FH1) domain. In higher mammals like human and mouse fifteen different formin isoforms are present. However the function and expression pattern of each and every formin in different adult tissues are not well characterized. Here we have found that multiple formins are expressing in each adult tissue of mouse, irrespective of their origin from the germ layer. Formins are also expressing from early stage of development to the adulthood in brain. The expression of many formins in a single tissue of adult mouse indicates that regulation of actin cytoskeleton dynamics by formins may be crucial for physiological processes like wound healing, tissue repairing, exocytosis, endocytosis, synapse formation and maintenance. Expression of FMNL2 and Fhdc1 are high in adult mouse brain as compare to embryonic stages. Higher expression of FMNL2 and Fhdc1 indicates that FMNL2 and Fhdc1 might be very important for the adult brain functions.

D008841:Actin Cytoskeleton
D000199:Actins
D000367:Age Factors
D000818:Animals
D001921:Brain
D005326:Fetal Proteins
D000080865:Formins
D051379:Mice
D008810:Mice, Inbred C57BL
D008840:Microfilament Proteins
D009419:Nerve Tissue Proteins
D009687:Nuclear Proteins
D009928:Organ Specificity
D020033:Protein Isoforms
D017434:Protein Structure, Tertiary

Expression Formin Tissue Actin Distribution


Sense of Coherence, Compassionate Love and Coping in International Leaders during the Transition into the Fourth Industrial Revolution.

Abstract: Contemporary workplaces are influenced by rapid changes, high levels of competition, increasing complexities and internationalisation processes. At the edge of the Fourth Industrial Revolution (4IR), insecurities and anxieties are high, and leaders are encouraged more than ever to lead employees with meaningful vision and prudence in order to make use of employees' strengths, and ensure mental health and well-being. The aim of this article is to present new insights into salutogenesis, particularly sense of coherence (SOC), compassionate love (CL), and coping (C) in leaders with different cultural backgrounds. This study strengthens the idea that CL is a coping mechanism. This coping mechanism can be used by leaders to establish a resilient and salutogenic organisations. This article explores the subjective perspectives of 22 international leaders from five different countries and their views regarding SOC, CL and C through a qualitative research approach, using a qualitative online questionnaire for data collection and content analysis for data analysis. The findings on the perspectives of leaders provide new and original insights into how SOC, CL and C are connected, and how these concepts contribute to healthy organisations which are on their way to the transition into the 4IR. Conclusions are drawn. Recommendations for future research and practice are given.

salutogenesis
sense of coherence (SOC)
compassionate love (CL)
coping (C)
4IR workplaces
leadership
societal and cultural challenges


The Eating Disorders Genetics Initiative (EDGI): study protocol.

Abstract:
BACKGROUND
The Eating Disorders Genetics Initiative (EDGI) is an international investigation exploring the role of genes and environment in anorexia nervosa, bulimia nervosa, and binge-eating disorder.

METHODS
A total of 14,500 individuals with eating disorders and 1500 controls will be included from the United States (US), Australia (AU), New Zealand (NZ), and Denmark (DK). In the US, AU, and NZ, participants will complete comprehensive online phenotyping and will submit a saliva sample for genotyping. In DK, individuals with eating disorders will be identified by the National Patient Register, and genotyping will occur using bloodspots archived from birth. A genome-wide association study will be conducted within EDGI and via meta-analysis with other data from the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED).

DISCUSSION
EDGI represents the largest genetic study of eating disorders ever to be conducted and is designed to rapidly advance the study of the genetics of the three major eating disorders (anorexia nervosa, bulimia nervosa, and binge-eating disorder). We will explicate the genetic architecture of eating disorders relative to each other and to other psychiatric and metabolic disorders and traits. Our goal is for EDGI to deliver "actionable" findings that can be transformed into clinically meaningful insights.

TRIAL REGISTRATION
EDGI is a registered clinical trial: clinicaltrials.gov NCT04378101 .

D001315:Australia
D052018:Bulimia Nervosa
D001068:Feeding and Eating Disorders
D055106:Genome-Wide Association Study
D006801:Humans
D015201:Meta-Analysis as Topic
D009520:New Zealand
D014481:United States

Eating disorders
Anorexia nervosa
Bulimia nervosa
Binge-eating disorder
Genome-wide association
Psychiatric genomics consortium
Psychiatric genetics
Social media


Analgesic Effect of Melittin on Oxaliplatin-Induced Peripheral Neuropathy in Rats.

Abstract: Oxaliplatin is a chemotherapeutic agent used for metastatic colon and other advanced cancers. Most common side effect of oxaliplatin is peripheral neuropathy, manifested in mechanical and cold allodynia. Although the analgesic effect of bee venom has been proven to be effective against oxaliplatin-induced peripheral neuropathy, the effect of its major component; melittin has not been studied yet. Thus, in this study, we investigated whether melittin has an analgesic effect on oxaliplatin-induced allodynia. Intraperitoneal single injection of oxaliplatin (6 mg/kg) induced mechanical and cold allodynia, resulting in increased withdrawal behavior in response to von Frey filaments and acetone drop on hind paw. Subcutaneous melittin injection on acupoint ST36 (0.5 mg/kg) alleviated oxaliplatin-induced mechanical and cold allodynia. In electrophysiological study, using spinal in vivo extracellular recording, it was shown that oxaliplatin-induced hyperexcitation of spinal wide dynamic range neurons in response to peripheral stimuli, and melittin administration inhibited this neuronal activity. In behavioral assessment, analgesic effect of melittin was blocked by intrathecal α1- and α2- adrenergic receptor antagonists administration. Based on these results, we suggest that melittin could be used as an analgesic on oxaliplatin-induced peripheral neuropathy, and that its effect is mediated by activating the spinal α1- and α2-adrenergic receptors.

Choi|Seunghwan|S|
Chae|Hyeon Kyeong|HK|
Heo|Ho|H|
Hahm|Dae-Hyun|DH|
Kim|Woojin|W|
Kim|Sun Kwang|SK|0000-0002-2649-6652

D058668:Adrenergic alpha-1 Receptor Antagonists

D058669:Adrenergic alpha-2 Receptor Antagonists

D010523:Peripheral Nervous System Diseases

melittin
oxaliplatin
cold allodynia
chemotherapy
mechanical allodynia
neuropathic pain


A study on the interaction between 3-spiro-piperidones and bovine serum albumin using spectroscopic approaches.

Abstract: The interaction between 3-spiro-2'-pyrrolidine-3'-spiro-3″-piperidine-2,3″-dione (PPD) and bovine serum albumin (BSA) in aqueous solution was studied using fluorescence and UV-vis spectroscopy. Fluorescence emission data revealed that BSA (1.00 × 10(-5)  mol/L) fluorescence was statically quenched by PPD at various concentrations, which implies that a PPD-BSA complex was formed. The binding constant (KA ), the number of binding sites (n) and the specific binding site of the PPD with BSA were determined. Energy-transfer efficiency parameters were determined and the mechanism of the interaction discussed. The thermodynamic parameters, ΔG, ΔH and ΔS, were obtained according to van't Hoff's equation, showing the involvement of hydrophobic forces in these interactions. The effect of PPD acting on the BSA conformation was detected by synchronous fluorescence.

Yu|Xianyong|X| Yao|Qing|Q| Tao|Hongwen|H| Yang|Ying|Y| Li|Lei|L| Zheng|Baishu|B| Zhu|Shizhong|S|

interaction
bovine serum albumin
3′-spiro-3″-piperidine-2,3″-dione
fluorescence spectroscopy
ultraviolet spectroscopy


Clinical application of magnetic resonance-guided focused ultrasound in Parkinson's disease: a meta-analysis of randomized clinical trials.

Abstract:
BACKGROUND
To evaluate the safety and efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) in the treatment of Parkinson's disease (PD).

METHODS
The databases of Medline, EMBASE, and the Cochrane Library were searched for eligible randomized controlled trials comparing focused ultrasound surgery (FUS) group vs. sham procedure group in PD. Weighted mean differences and standardized mean differences with corresponding 95% confidence intervals were used to summarize the primary outcome, namely, the effect of MRgFUS to improve limb tremor in PD patients and adverse events, and the secondary outcome, which is the effect of MRgFUS in improving the quality of life, activities of daily living, and non-motor symptoms.

RESULTS
The pooled analysis comprised 2 studies. The blinded phase lasted for 4 months in one experiment and up to 3 months in the other. The FUS group showed significant improvement in limb tremor on the treated side (SMD: - 1.20; 95% CI: - 2.06, - 0.34) and the ability to perform daily activities (SMD: - 0.86; 95% CI: - 1.41, - 0.32) compared to the sham group, but there were no significant group differences in other indicators. Of the process-related adverse events, dizziness (OR: 4.68; 95% CI: 1.20, 18.23) was more common in the treatment group, with no group differences in the remaining adverse events.

CONCLUSIONS
These findings suggest beneficial effects of MRgFUS in PD patients with no serious side effects. Larger multicenter studies are needed in the future to select the most appropriate target and surgical device setup parameters.

D016032:Randomized Controlled Trials as Topic

Focused ultrasound
Meta-analysis
Safety
Efficacy
Parkinson’s disease


Chemokine CCL2 enhances NMDA receptor-mediated excitatory postsynaptic current in rat hippocampal slices-a potential mechanism for HIV-1-associated neuropathy?

Abstract: Human immunodeficiency virus type 1 (HIV-1)-infected mononuclear phagocytes (brain macrophages and microglial cells) release proinflammatory cytokines and chemokines. Elevated levels of chemokine CC motif ligand 2 (CCL2, known previously as monocyte chemoattractant protein-1) have been detected in serum and cerebrospinal fluid (CSF) of HIV-1-infected individuals and the raised CCL2 in the CSF correlates with HIV-1-associated neurocognitive disorders. To understand how elevated CCL2 induces HIV-1-associated neuropathy, we studied effects of CCL2 on excitatory postsynaptic current (EPSCs) in the CA1 region of rat hippocampal brain slices using whole-cell patch recording techniques. The AMPA receptor (AMPAR)-mediated EPSC (EPSCAMPAR) and N-Methyl-D-aspartate (NMDA) receptor (NMDAR)-mediated EPSCs (EPSCNMDAR) were isolated pharmacologically. Bath application of CCL2 produced a significant enhancement of the amplitudes of EPSCs, EPSCAMPAR and EPSCNMDAR. Further studies revealed that CCL2 potentiated NMDAR subtype NR2A-mediated EPSC (EPSCNR2AR) and NR2B-mediated EPSC (EPSCNR2BR). To determine the site of action, we recorded spontaneous mini EPSCs (mEPSC) before and during bath application of CCL2. Our results showed that CCL2 decreased inter event interval (IEI) and increased the frequency of mEPSCs without change on the amplitude, suggesting a presynaptic site of CCL2 action. CCL2 was also found to injure primary rat hippocampal neuronal cultures and neuronal dendrites in the CA1 region of hippocampal slices. The CCL2-associated neuronal and dendritic injuries were blocked by a specific NMDAR antagonist or by a CCR2 receptor antagonist, indicating that CCL2-associated neural injury was mediated via NMDARs and/or CCR2 receptors. Taken together, these results suggest a potential role CCL2 may play in HIV-1-associated neuropathology.

Chemokine
CCL2
HIV-1-associated neuropathy
NMDA receptors, EPSCs, hippocampus


The Long Noncoding RNA 150Rik Promotes Mesangial Cell Proliferation via miR-451/IGF1R/p38 MAPK Signaling in Diabetic Nephropathy.

Abstract:
BACKGROUND/AIMS
Diabetic nephropathy (DN) as the primary cause of end-stage kidney disease is a common complication of diabetes. However, the initiating molecular events triggering DN are unknown. Recently, long noncoding RNAs (lncRNAs) have been shown to play important roles in DN.

METHODS
The expression level of lncRNA 1500026H17Rik (150Rik for short) was measured by qRT-PCR (quantitative real-time PCR). Cell proliferation ability was detected by 5-Ethynyl-2'-deoxyuridine (EdU). The relationship between 150Rik and microRNA 451 (miR-451) was examined by luciferase assay and RNA immunoprecipitation (RIP) assay. Finally, the effect of 150Rik on cell proliferation through the miR-451/insulin-like growth factor 1 receptor (IGF1R)/mitogen-activated protein kinases (p38MAPK) pathway was detected by EdU, flow cytometry analysis, western blot.

RESULTS
We found that 150Rik, an evolutionarily conserved lncRNA, was significantly upregulated in renal tissue of db/db DN mice and in mesangial cells (MCs) cultured under a high glucose condition. Further, overexpression or knockdown of 150Rik was found to regulate cell proliferation in MCs. Moreover, 150Rik was found to interact with miR-451 in both a direct and argonaute-2 (Ago2)-dependent manner. Results also revealed that overexpression of 150Rik inhibited cell proliferation through the miR-451/IGF1R/p38MAPK pathway in MCs under the high glucose condition, while knockdown of 150Rik increased cell proliferation via the miR-451/IGF1R/p38MAPK pathway.

CONCLUSION
Taken together, these results provide new insight into the association between 150Rik and the miR-451/IGF1R/p38MAPK signaling pathway during DN progression.

Zhang|Yajuan|Y| Sun|Yan|Y| Peng|Rui|R| Liu|Handeng|H| He|Weihao|W| Zhang|Luyu|L| Peng|Huimin|H| Zhang|Zheng|Z|

D048051:p38 Mitogen-Activated Protein Kinases

Cell proliferation
miR-451
Diabetic nephropathy
lncRNA


Effects of Phosphatidylserine Source of Docosahexaenoic Acid on Cerebellar Development in Preterm Pigs.

Abstract: Preterm birth, a major contributor to infant mortality and morbidity, impairs development of the cerebellum, the brain region involved in cognitive processing and motor function. Previously, we showed that at term-equivalent age, preterm pigs that received formula supplemented with docosahexaenoic acid (DHA) esterified to phosphatidylserine (PS) had cerebellar weights similar to those of newborn term pigs and were heavier than control preterm pigs. However, whether PS-DHA promotes the development of specific cerebellar cell populations or enhances key developmental processes remains unknown. Here we investigated the effects of the PS-DHA on development of the cerebellum in preterm pigs delivered via caesarean section and reared for ten days on a milk replacer with either PS-DHA (experimental group) or sunflower oil (control group). Upon necropsy, key cerebellar populations were analyzed using immunohistochemistry. Consumption of PS-DHA was associated with the expansion of undifferentiated granule cell precursors and increased proliferation in the external granule cell layer (EGL). Preterm pigs that received PS-DHA also had significantly fewer apoptotic cells in the internal granule cell layer (IGL) that contains differentiated granule neurons. PS-DHA did not affect the number of differentiating granule cells in the inner EGL, thickness of the inner EGL, density of Purkinje cells, or Bergmann glial fibers, or diameter of Purkinje cells. Thus, PS-DHA may support cerebellar development in preterm subjects by enhancing proliferation of granule cells, a process specifically inhibited by preterm birth, and increasing the survival of granule cells in the IGL. These findings suggest that PS-DHA is a promising candidate for clinical studies directed at enhancing brain development.

Chizhikov|Daniel|D|
Buddington|Randal K|RK|
Iskusnykh|Igor Y|IY|0000-0002-1207-6075

phosphatidylserine
pig
cerebellum
docosahexaenoic acid (DHA)
granule cells
proliferation
brain development
apoptosis
preterm infants


Health literacy and health outcomes in chronic obstructive pulmonary disease.

Abstract:
BACKGROUND
There is little information worldwide about the impact of health literacy (HL) on clinical outcomes of COPD. Our aim was to quantify inadequate HL in Spain, as measured by the Short Assessment of Health Literacy for Spanish Adults questionnaire, and to examine the associations between HL and both COPD outcomes and health status.

METHODS
296 COPD patients of 68(SD = 9) years and a FEV1%predicted of 53%(SD = 18%) were enrolled and followed-up for one year. 59% showed "inadequate" HL.

RESULTS
Individuals with inadequate HL were older (70[SD = 9] vs 65[SD = 8] years; p < 0.001) and had less knowledge of their disease, as measured by the low HL-COPD questionnaire, (6.9[SD = 2.3] vs 7.5[SD = 1.9]; p < 0.001). While their lung function was no different, they reported significant differences in mMRC (1.6[SD = 1] vs 1.4[SD = 1]; p < 0.001), CAT (19.2[SD = 8.1] vs 18.3[SD = 7.5]; p = 0.049), and EQ-5 (3.1[SD = 2.2] vs 2.3[SD = 1.9]; p < 0.00). Those with inadequate HL had also higher risk of having ≥2 comorbidities (OR = 1.87; 95%CI = 1.14-3.08), need of assistance (OR = 2.5; 95%CI = 1.5-4.2), anxiety/depression (OR = 1.9; 95%CI = 1.2-3.0), admissions or visits to the emergency department (OR = 1.70; 95%CI = 1.1-2.7), and all-cause deaths in the following year (3.8% (SE = 1.1%) vs 0%; p = 0.051).

CONCLUSIONS
Inadequate HL is prevalent among COPD patients and it is related to health status and relevant clinical outcomes of the disease. HL needs to be considered when planning the care for COPD patients.

Puente-Maestu|Luis|L|
Calle|Myriam|M|
Rodríguez-Hermosa|Juan Luis|JL|
Campuzano|Anna|A|
de Miguel Díez|Javier|J|
Álvarez-Sala|Jose Luis|JL|
Puente-Andues|Luis|L|
Pérez-Gutiérrez|Maria Joselín|MJ|
Lee|Shoou-Yih D|SY|

D029424:Pulmonary Disease, Chronic Obstructive

Health outcomes
COPD
Health status
Daily living activities
Dependence
Utility
Utilization


Aqueous photocatalytic degradation of selected micropollutants by Pd-modified titanium dioxide in three photoreactor types.

Abstract: The goals of the present study were to synthesise highly efficient Pd-TiO2 photocatalyst, to characterise its performance in slurry in smaller scale and to investigate its performance in the aqueous photocatalytic oxidation of three antibiotics: doxycycline, sulphamethizole and amoxicillin. The performance of the photocatalyst was evaluated in an open batch slurry reactor equipped with a fluorescent long-wavelength ultraviolet (UVA) lamp (0.2 L). With the fastest degrading doxycycline, experimental research was continued in a fixed-bed continuous flow photoreactor (0.13 L), with the Pd-TiO2 photocatalyst attached to a glass plate, and a medium laboratory-scale three-phase fluidised-bed reactor (2 L) equipped with four fluorescent UVA lamps, with the photocatalyst attached to the surface of expanded clay granules employed as the bed material. While showing very high activity in the batch slurry reactor, far surpassing P25 Aeroxide, the performance of Pd-TiO2 with doxycycline was comparable to P25 in the semi-continuous reactors.

Klauson|Deniss|D| Šakarašvili|Marko|M| Pronina|Natalja|N| Krichevskaya|Marina|M| Kärber|Erki|E| Mikli|Valdek|V|

photoreactor
fluidised-bed reactor
Tetracyclines
penicillins
sulphonamides


The effects of magnesium on the course of atrial fibrillation and coagulation in patients with atrial fibrillation undergoing mitral valve annuloplasty.

Abstract:
BACKGROUND
Atrial fibrillation (AF) is the most common cardiac arrhythmia. Magnesium has been reported to be effective in reducing the incidence or prophylaxis of AF. Magnesium is also an essential constituent of many enzyme systems and plays a physiological role in coagulation regulation. The aim of the present study was to examine the effects of magnesium, whether magnesium infusion might decrease the incidence of AF and induce hypocoagulable state in patients with AF, who were undergoing mitral valve annuloplasty.

METHODS
This prospective laboratory study was performed using blood from patients with AF undergoing mitral valve annuloplasty. The radial artery was punctured with a 20 gauge catheter and used for monitoring continuous arterial pressure and blood sampling. After anesthesia induction, 4 g of magnesium was mixed with 100 ml normal saline and infused for 5 minutes. Magnesium, calcium, activated clotting time (ACT) and thromboelastographic parameters were checked before and 60 minutes after the magnesium infusion. The electrocardiography changes after magnesium infusion were also checked before commencing cardiopulmonary bypass.

RESULTS
After magnesium infusion, the serum level of magnesium increased significantly but serum calcium did not change significantly. ACT did not change significantly before or after magnesium infusion. The thromboelastographic parameters showed no significant changes before or after magnesium infusion. None of the patients converted to sinus rhythm from AF after the magnesium infusion.

CONCLUSIONS
A magnesium infusion did not influence the course of AF and coagulation in patients during prebypass period with AF undergoing mitral valve annuloplasty.

Kang|Woon-Seok|WS| Yun|Hye-Jeong|HJ| Han|Sang-Joo|SJ| Kim|Hye-Young|HY| Kim|Duk-Kyung|DK| Lim|Jeong-Ae|JA| Woo|Nam-Sik|NS| Kim|Seong-Hyop|SH|

Magnesium
Atrial fibrillation
Mitral valve annuloplasty
Thromboelastography


Modulation of Type I Interferon System by African Swine Fever Virus.

Abstract: African Swine Fever Virus (ASFV) has tropism for macrophages, which seems to play a crucial role in disease pathogenesis and viral dissemination. Previous studies showed that ASFV developed mechanisms to evade type I interferon (IFN) responses. Hence, we analyzed the ability of ASFV strains of diverse virulence to modulate IFN-β and IFN-α responses. Porcine monocyte-derived macrophages un-activated (moMΦ) or activated with IFN-α (moMΦ + FN-α) were infected with virulent (22653/14) or attenuated (NH/P68) ASFV strains, and expressions of IFN-β and of 17 IFN-α subtypes genes were monitored over time. ASFV strains of diverse virulence induced different panels of IFN genes: infection of moMΦ with either strains caused statistically significant up-regulation of IFN-α3, -α7/11, whereas only attenuated NH/P68 determined statistically significant up-regulation of IFN-α10, -α12, -α13, -α15, -α17, and IFN-β. Infection of activated moMΦ with either strains resulted in up-regulation of IFN-β and many IFN-α subtypes, but statistical significance was found only for IFN-α1, -α10, -α15, -α16, -α17 in response to NH/P68-infection only. These data revealed differences in type I IFNs expression patterns, with differences between strains of diverse virulence. In addition, virulent 22653/14 ASFV seems to have developed mechanisms to suppress the induction of several type I IFN genes.

African swine fever
IFN-β
monocyte-derived macrophages
IFN-α subtypes
INF-α activation


Type 1 diabetic patients have better endothelial function after simultaneous pancreas-kidney transplantation than after kidney transplantation with continued insulin therapy.

Abstract: The purpose of this study was to analyse the influence of simultaneous pancreas-kidney or kidney transplantation on endothelial function and systemic inflammation in type 1 diabetic patients with end-stage renal disease. In 39 simultaneous pancreas-kidney, 39 type 1 diabetic kidney and 52 non-diabetic kidney recipients, flow-mediated dilatation was measured. Additionally, blood glycated haemoglobin, serum creatinine and lipids, plasma nitrites [Formula: see text] and nitrates, asymmetric dimethylarginine, soluble vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and E-selectin, high-sensitivity C-reactive protein, tumour necrosis factor-α, interleukin 1β and interleukin 6 concentrations were assessed. During 58 ± 31 months follow-up period, flow-mediated dilatation and [Formula: see text] were greater in simultaneous pancreas-kidney than in type 1 diabetic kidney recipients [10.4% ± 4.7% vs 7.7% ± 4.2%, p < 0.05 and 0.94 (0.74-1.34) vs 0.24 (0.20-0.43) μmol/L, p < 0.01, respectively]. In type 1 diabetic patients after simultaneous pancreas-kidney or kidney transplantation, [Formula: see text] correlated with flow-mediated dilatation (r = 0.306, p < 0.05) and with blood glycated haemoglobin (r = -0.570, p < 0.001). The difference in [Formula: see text] was linked to blood glycated haemoglobin and estimated glomerular filtration rate, whereas the difference in flow-mediated dilatation was linked to [Formula: see text]. The levels of inflammatory markers (except soluble vascular cell adhesion molecule-1) were similar in simultaneous pancreas-kidney and type 1 diabetic kidney recipients. Improved endothelial function in type 1 diabetic patients with end-stage renal disease after simultaneous pancreas-kidney compared to kidney transplantation is associated with normalisation of glucose metabolism but not with improvement in plasma pro-inflammatory cytokines.

Ziaja|Jacek|J|
Kowalik|Adrian P|AP|
Kolonko|Aureliusz|A|
Kamińska|Dorota|D|
Owczarek|Aleksander J|AJ|
Kujawa-Szewieczek|Agata|A|
Kusztal|Mariusz A|MA|
Badura|Joanna|J|
Bożek-Pająk|Dominika|D|
Choręza|Piotr|P|
Zakrzewska|Agnieszka|A|
Król|Robert|R|
Chłopicki|Stefan|S|
Klinger|Marian|M|
Więcek|Andrzej|A|
Chudek|Jerzy|J|
Cierpka|Lech|L|


Modifying cognition and behavior with electrical microstimulation: implications for cognitive prostheses.

Abstract: A fundamental goal of cognitive neuroscience is to understand how brain activity generates complex mental states and behaviors. While neuronal activity may predict or correlate with behavioral responses in a cognitive task, the use of electrical microstimulation presents the possibility to augment such correlational findings with direct evidence for causal relationships. Although microstimulation has been used for many years as a tool for mapping sensory and motor function, its role in learning, memory and decision-making has emerged only recently. Focal microstimulation of higher cortical areas can produce complex mental states and sequences of action. However, the relationship between the locus of stimulation and the percepts or actions evoked is often stereotyped and inflexible. The challenge is to develop stimulation systems that do not have fixed output but can flexibly contribute to complex cognitive and behavioral tasks. We discuss how microstimulation has been instrumental in manipulating a wide spectrum of cognitive functions including working memory, perceptual decisions and executive control by enhancing attention, re-ordering temporal sequence of saccades, improving associative learning or cognitive performance. For example, stimulation in prefrontal, parietal and sensory cortices may establish causal effects on decision-making, while microstimulation of inferotemporal cortex or caudate nucleus enhances associative learning. Building cognitive prosthetics based on the insights gleaned from such studies may depend on the development of multiple-input, multiple-output (MIMO) devices that allow subjects to control stimulation with their own thoughts in a closed-loop system.

Causal relationship
IT
Learning
Perception
Attention
Inferotemporal cortex
Caudate nucleus
CN
Dorsolateral prefrontal cortex
FEF
Frontal eye field
MF
MT
Memory/movement field
Middle temporal visual area
RF
Receptive field
SEF
SMA
Supplementary eye field
Supplementary motor area
dlPFC

P P P P P P P U M U U U U M M U U U U U M U


spe-43 is required for sperm activation in C. elegans.

Abstract: Successful fertilization requires that sperm are activated prior to contacting an oocyte. In C. elegans, this activation process, called spermiogenesis, transforms round immobile spermatids into motile, fertilization-competent spermatozoa. We describe the phenotypic and genetic characterization of spe-43, a new component of the spe-8 pathway, which is required for spermiogenesis in hermaphrodites; spe-43 hermaphrodites are self-sterile, while spe-43 males show wild-type fertility. When exposed to Pronase to activate sperm in vitro, spe-43 spermatids form long rigid spikes radiating outward from the cell periphery instead of forming a motile pseudopod, indicating that spermiogenesis initiates but is not completed. Using a combination of recombinant and deletion mapping and whole genome sequencing, we identified F09E8.1 as spe-43. SPE-43 is predicted to exist in two isoforms; one isoform appears to be a single-pass transmembrane protein while the other is predicted to be a secreted protein. SPE-43 can bind to other known sperm proteins, including SPE-4 and SPE-29, which are known to impact spermiogenesis. In summary, we have identified a membrane protein that is present in C. elegans sperm and is required for sperm activation via the hermaphrodite activation signal.

Krauchunas|Amber R|AR|
Mendez|Ernesto|E|
Ni|Julie Zhouli|JZ|
Druzhinina|Marina|M|
Mulia|Amanda|A|
Parry|Jean|J|
Gu|Sam Guoping|SG|
Stanfield|Gillian M|GM|
Singson|Andrew|A|

D020133:Reverse Transcriptase Polymerase Chain Reaction

Sperm
Sperm activation
C. elegans
Spermiogenesis


Restoration of the immune function as a complementary strategy to treat Chronic Lymphocytic Leukemia effectively.

Abstract: Chronic Lymphocytic Leukemia (CLL) is a hematological malignancy characterized by uncontrolled proliferation of B-cells and severe immune dysfunction. Chemo(immuno)therapies (CIT) have traditionally aimed to reduce tumor burden without fully understanding their effects on the immune system. As a consequence, CIT are usually associated with higher risk of infections, secondary neoplasms and autoimmune disorders. A better understanding of the biology of the disease has led to the development of therapeutic strategies which not only act against malignant B-cells but also reactivate and enhance the patient's own anti-tumor immune response. Here, we review the current understanding of the underlying interplay between the malignant cells and non-malignant immune cells that may promote tumor survival and proliferation. In addition, we review the available evidence on how different treatment options for CLL including CIT regimens, small molecular inhibitors (i.e, BTK inhibitors, PI3K inhibitors, BCL-2 inhibitors) and T-cell therapies, affect the immune system and their clinical consequences. Finally, we propose that a dual therapeutic approach, acting directly against malignant B-cells and restoring the immune function is clinically relevant and should be considered when developing future strategies to treat patients with CLL.

Immune function
Chronic Lymphocytic Leukemia
CLL
Ibrutinib


Sonographic assistance in the process of internal jugular vein catheterization.

Abstract:
OBJECTIVE
Introduction: The use of ultrasound assistance of major vessels simplifies and facilitates vascular catheterization under conditions that significantly complicate gaining vascular access and reduces the risk of complications. The aim of the work is technical improvement of catheterization of major vessels, in particular, of the jugular vein, under guidance of ultrasound.

PATIENTS AND METHODS
Materials and Methods:The result of catheterization of the internal jugular vein in 126 patients of intensive care unit, was analyzed. In 75 patients Seldinger's catheterization was used, taking into account anatomical markings, in 51 patients a method using ultrasound navigation was applied.

RESULTS
Results: The advantages of catheterization of the main vessels under the guidance of ultrasound are established, in particular, control over the procedure and reduction of the time of its carrying out, the possibility of catheterization at the first attempt and the absence of complications associated with the procedure.

CONCLUSION
Conclusions: The greatest effectiveness of internal jugular vein catheterization under the guidance of ultrasound assistency has been proved, which reduces the time of the procedure by 23.1%, reduces the number of attempts of catheterization, enables to monitor the progress of the procedure and prevent complications by using ultrasound navigation in 100% of the cases.

Karlova|Olena O|OO|
Kaminsky|Vyacheslav V|VV|
Kuzminska|Olena V|OV|

jugular vein
catheterization
complications
Ultrasound diagnosis


Internal Spermatic Vein Insufficiency in Varicoceles: A Different Entity in Adults and Adolescents?

Abstract:
OBJECTIVE
The purpose of this study was to determine whether phlebographic features can be used to discriminate adult from adolescent varicocele.

MATERIALS AND METHODS
Left and right internal spermatic venograms of 191 adolescents (< 17 years) and 224 adults (≥ 25 years) were anonymized and evaluated. Phlebographic radioanatomic features (valves, duplications, collaterals, and classifications) were compared and analyzed with univariate tests.

RESULTS
Insufficiency of the left internal spermatic vein (ISV) was confirmed in 409 of the 415 (99%) patients. Adults had no spontaneous opacification of the ISV during venography twice as frequently as adolescents (p = 0.001), a complex outflow into the renal vein 2.2 times as often (p = 0.021), and significantly more collaterals (p = 0.030). Adolescents had a significantly lower number of competent valves and significantly more instances of nutcracker phenomenon (p = 0.001). According to the Bähren classification, the distribution of the types of ISVs was significantly different between adults and adolescents (p = 0.009). Insufficiency of the right ISV was encountered 2.4 times as frequently in adults as in adolescents (p < 0.001). In adults the maximum diameter of the ISV was significantly larger (p = 0.023). Bilateral ISV insufficiency was 2.2 times as frequent in adults (p < 0.001) as in adolescents.

CONCLUSION
Left-sided varicoceles in adults are distinct from those in adolescents. In adults, reflux is likely to be induced via collateral pathways, whereas in adolescents congenital venous abnormalities are predominantly present. The higher prevalence and the greater diameter of a right insufficient ISV in adults, combined with the absence of venous anatomic differences, supports the hypothesis that right-sided varicocele is an evolutive disease.

Vanlangenhove|Peter|P|
Dhondt|Elisabeth|E|
Van Maele|Georges|G|
Van Waesberghe|Sofie|S|
Delanghe|Ellen|E|
Defreyne|Luc|L|

varicocele adults adolescents pathophysiology phlebography


Consequences of different growth rates in broiler breeder and layer hens on embryogenesis, metabolism and metabolic rate: A review.

Abstract: Intensive genetic selection of broiler breeders and layer hens for economically important production traits, which has been carried out for almost a century, resulted in considerable differences in the mechanisms of growth and development and, thus, in avian metabolism, both during embryogenesis and after hatching. Selection for meat production (broiler breeders) and eggs (layer hens) led to increased productivity but also brought about metabolic disorders. That intensive genetic selection of broiler breeders and layer hens is effective is seen, for example, in the differences in growth and development, metabolism of the yolk sac, hormones and lipids, gas exchange, and thermogenesis. Due to genetic proximity and different developmental mechanisms in broiler breeders and layer hens, avian embryos and chicks serve as excellent models for fundamental scientific research. This review paper discusses the consequences of different growth rates as a result of long-term genetic selection on embryonic development and metabolic rate of broilers and layers. The evidence presented herein indicates that it would be worth comparing these issues in a meta-analysis.

broiler breeder
layer hen
metabolism
genetic selection
development


Cost-effectiveness of valbenazine compared with deutetrabenazine for the treatment of tardive dyskinesia.

Abstract:
AIMS
To evaluate clinical and economic outcomes associated with valbenazine compared with deutetrabenazine in patients with tardive dyskinesia (TD) using a model that accounts for multiple dimensions of patient health status.

MATERIALS AND METHODS
A discretely integrated condition event model was developed to evaluate the cost-effectiveness of treatment with valbenazine and deutetrabenazine in a synthetic cohort of 1,000 patients with TD who were receiving antipsychotic medication to treat an underlying psychiatric disorder. Clinical inputs were derived from relevant clinical trials or from publicly available sources. Patients were assessed over 1 year using ≥50% improvement from baseline in Abnormal Involuntary Movement Scale (AIMS) total score as the primary definition of response. Response at 1 year using Clinical Global Impression of Change (CGIC) score ≤2 was also assessed. Health outcomes included quality-adjusted life years (QALYs), life years, proportion responding to treatment at 1 year, and number of psychiatric relapses.

RESULTS
Regardless of the definition used for response, patients treated with valbenazine were more likely to have responded to treatment at 1 year, lived longer, and accrued more QALYs than patients who received deutetrabenazine. Using the AIMS response criterion, the incremental cost-effectiveness ratio was $9,951/QALY for valbenazine compared with deutetrabenazine. By comparison, using the CGIC response criterion valbenazine dominated deutetrabenazine with valbenazine-treated patients accumulating more QALYs (3.4 vs 3.3 years) and incurring lower lifetime costs ($252,311 vs $283,208) than deutetrabenazine-treated patients.

LIMITATIONS
There are no head-to-head trials of valbenazine and deutetrabenazine, so probabilities of response used in the model were calculated based on an indirect treatment comparison of results from individual trials with one drug or the other, using only those metrics reported across trials.

CONCLUSIONS
In patients with TD, treatment with valbenazine is highly cost-effective compared with deutetrabenazine.

valbenazine
deutetrabenazine
Tardive dyskinesia
I11
I13
VMAT2 inhibitors
cost effectiveness


Probability and amount of medicines expenditure according to health insurance status in Kenya: A household survey in eight counties.

Abstract:
BACKGROUND
National and county governments in Kenya have introduced various health insurance schemes to protect households against financial hardship as a result of large health expenditure. This study examines the relationship between health insurance and medicine expenditure in eight counties in Kenya.

METHODS
A cross-sectional study of collected primary data via household survey in eight counties was performed. Three measures of medicine expenditure were analysed: the probability of any out-of-pocket expenditure (OOPE) on medicines in the last 4 weeks; amount of OOPE on medicines; and OOPE on medicines as a proportion of total OOPE on health.

RESULTS
Out of the 452 individuals, those with health insurance (n = 225) were significantly different from individuals without health insurance (n = 227): overall, they were older, had a higher level of educational attainment and possessed more assets. Adjusting for covariates, individuals with health insurance had a reduced probability of OOPE on medicines (0.40, CI95% 0.197-0.827) and spent proportionally less on medicines out of total health expenditure (0.50, CI95% 0.301-0.926).

CONCLUSIONS
Kenya has made great strides to scale up Universal Health Coverage including access to medicines. Prioritising enrollment of low-income individuals with non-communicable diseases can accelerate access to medicines and financial protection.

medicines expenditure
health insurance
Kenya
universal health coverage


Characterization of the interactions of ADAMTS13 CUB1 domain to WT- and GOF-Spacer domain by molecular dynamics simulation.

Abstract: Metalloprotease ADAMTS13 specifically cleaves VWF (von Willebrand Factor) to prevent excessive platelet aggregation and thrombus formation at the sites of vascular injury. To avoid non-specific cleavage, ADAMTS13 has the auto-inhibition effect in which the Spacer domain in N-terminal interacts with the CUB1 domain in C-terminal, resulting in decreased proteolytic activity. Previous studies reported that exosite-3 in the Spacer domain was a key binding site in the Spacer-CUB1 interaction. When exosite-3 was mutated (R660K/F592Y/R568K/Y661F/Y665F, GOF), the auto-inhibition of ADAMTS13 was disrupted and the enzymatic activity was markedly increased. However, the characteristics of the Spacer-CUB1 interaction is not fully understood. Here, we constructed the model of Spacer-CUB1 complex by homologous modeling and molecular docking to characterize the Spacer-CUB1 binding and predict key amino acid residues via molecular dynamics simulation. Our data showed that G607-S610 was a non-reported potential binding site in the Spacer domain; GOF mutation attenuated the formation of hydrogen bond between exosite-3 and the CUB1 domain; Residues E1231, R1251, L1258, D1259 and T1261 in the CUB1 domain might play an important role in the Spacer-CUB1 interaction. Our study advances the understanding of the structural basis of the auto-inhibition of ADAMTS13 and provides information about the key residues in the binding interface.

Yang|Junxian|J| Wu|Zhiwei|Z| Xie|Xubin|X| Liu|Guangjian|G| Fang|Ying|Y| Wu|Jianhua|J| Lin|Jiangguo|J|

D001665:Binding Sites
D062105:Molecular Docking Simulation
D056004:Molecular Dynamics Simulation
D059748:Proteolysis
D014841:von Willebrand Factor

ADAMTS13
CUB1
Molecular dynamics simulation
VWF
Auto-inhibition
Spacer


In vivo reflectance confocal microscopy features of cutaneous microcirculation and epidermal and dermal changes in diffuse systemic sclerosis and correlation with histological and videocapillaroscopic findings.

Abstract:
BACKGROUND
Videocapillaroscopy of the nail fold is the current gold standard to assess progressive changes of the capillary network in patients with systemic sclerosis (SSc). Reflectance confocal microscopy (RCM) is a non-invasive optical imaging tool that allows in vivo visualization of the skin structures and cutaneous microcirculation.

OBJECTIVE
To investigate qualitative and quantitative changes of the cutaneous microcirculation and dermal-epidermal alterations of SSc patients by RCM and to correlate the images with findings of videocapillaroscopy and histology.

METHODS
Ten patients affected by diffuse-type SSc with skin involvement and 10 healthy controls were enrolled. All subjects underwent RCM of the dorsal and ventral surfaces of the middle third of the left forearm and nailfold videocapillaroscopy. Skin biopsies for histological and immunohistochemical investigations were taken from 5 patients and 2 healthy controls.

RESULTS
At RCM observation, the diameter, perimeter and area of cutaneous capillaries were significantly increased in comparison to healthy controls, as histologically confirmed, whereas blood flow speed was significantly slower. Videocapillaroscopy showed a pathologic pattern of disease activity in 8 SSc patients and was non-specific in the remaining 2. In addition, RCM showed epidermal atrophy, flattening of rete ridges and dermal fibrosis in 7 SSc patients with long-standing disease but not in 3 patients with a recent onset.

CONCLUSION
RCM provides measurable morphological and functional findings of microcirculation in patients suffering from diffuse-type SSc. These findings can integrate with, but not substitute, those provided by standard videocapillaroscopy. In addition, unlike videocapillaroscopy, RCM allows the investigation of epidermal and dermal changes.

Venturini|Marina|M| Arisi|Mariachiara|M| Zanca|Arianna|A| Cavazzana|Ilaria|I| Gonzàlez|Salvador|S| Franceschini|Franco|F| Calzavara-Pinton|Piergiacomo|P|

reflectance confocal microscopy
systemic sclerosis
videocapillaroscopy
cutaneous capillaries


Physical Mechanisms of Bacterial Killing by Histones.

Abstract: Antibiotic resistance is a global epidemic, becoming increasingly pressing due to its rapid spread. There is thus a critical need to develop new therapeutic approaches. In addition to searching for new antibiotics, looking into existing mechanisms of natural host defense may enable researchers to improve existing defense mechanisms, and to develop effective, synthetic drugs guided by natural principles. Histones, primarily known for their role in condensing mammalian DNA, are antimicrobial and share biochemical similarities with antimicrobial peptides (AMPs); however, the mechanism by which histones kill bacteria is largely unknown. Both AMPs and histones are similar in size, cationic, contain a high proportion of hydrophobic amino acids, and possess the ability to form alpha helices. AMPs, which mostly kill bacteria through permeabilization or disruption of the biological membrane, have recently garnered significant attention for playing a key role in host defenses. This chapter outlines the structure and function of histone proteins as they compare to AMPs and provides an overview of their role in innate immune responses, especially regarding the action of specific histones against microorganisms and their potential mechanism of action against microbial pathogens.

Antimicrobial peptides
Antimicrobial synergy
Host-microbe interactions
LL-37
Mammalian histones
Neutrophil extracellular traps


Myocardial T1 mapping using SMART1 Map and MOLLI mapping in asymptomatic patients with recent extracardiac sarcoidosis.

Abstract:
INTRODUCTION
Sarcoidosis is a systemic granulomatous disease affecting in particular the respiratory tract. Cardiac magnetic resonance (CMR), including a measurement of T1 relaxation time, could potentially detect early stadia of sarcoidosis of the heart. The study aims to assess T1 mapping in the detection of early cardiac involvement in asymptomatic patients with sarcoidosis.

METHODS
One hundred and twenty patients with extracardiac sarcoidosis and without any heart disease history were included. One hundred and thirteen of them underwent a CMR examination. The mean time from the diagnosis of sarcoidosis was 0.8 (0.2-3.3) years. Cine images for the assessment of left ventricular (LV) functional parameters and pre- and post-contrast saturation method using adaptive recovery times for cardiac T1 mapping (SMART1 Map) and modified Look-Locker inversion recovery (MOLLI) images were acquired for the assessment of native T1 relaxation time and extracellular volume (ECV). The measured parameters were compared between sarcoidosis patients and 22 controls.

RESULTS
The sarcoidosis patients had normal global and regional systolic LV function-LV ejection fraction 65 ± 5% versus 66 ± 7% (p NS). The mean native T1 relaxation times were not prolonged-1465 ± 93 ms versus 1480 ± 88 ms (p NS) measured by SMART1 Map and 1317 ± 60 ms versus 1313 ± 83 ms (p NS) measured using a MOLLI sequence. Similarly, the mean ECV values did not increase-16.9 ± 3.9% versus 17.9 ± 3.7% (p NS) measured by SMART1 Map and 30.9 ± 2.9% versus 31.6 ± 8.3% (p NS) measured using a MOLLI sequence.

CONCLUSION
Myocardial native T1 relaxation times were not prolonged and ECV was not increased in asymptomatic patients with extracardiac sarcoidosis.

Panovský|Roman|R|0000-0001-8489-132X
Doubková|Martina|M|
Holeček|Tomáš|T|
Máchal|Jan|J|
Feitová|Věra|V|
Masárová|Lucia|L|
Opatřil|Lukáš|L|
Mojica-Pisciotti|Mary Luz|ML|
Kincl|Vladimír|V|

sarcoidosis
cardiac magnetic resonance
extracellular volume
parametric mapping


Consistent safety and tolerability of Valtoco® (diazepam nasal spray) in relationship to usage frequency in patients with seizure clusters: Interim results from a phase 3, long-term, open-label, repeat-dose safety study.

Abstract:
OBJECTIVE
Need for rescue therapy differs among patients with seizure clusters. Diazepam nasal spray is approved to treat seizure clusters in patients with epilepsy ≥6 years of age. This analysis used interim data from a phase 3 safety study to assess safety profile and effectiveness of diazepam nasal spray using average number of doses/month as a proxy measurement.

METHODS
This phase 3, open-label, repeat-dose, safety study of diazepam nasal spray enrolled patients (6-65 years) with epilepsy and need of benzodiazepine rescue. Patients were stratified by average number of doses/month (<2, moderate frequency; 2-5, high frequency; >5, very-high frequency). Safety was evaluated based on treatment-emergent adverse events (TEAEs), assessed nasal irritation, and olfaction. The proportion of treatments given as a second dose was used as an exploratory proxy for effectiveness.

RESULTS
Of 175 enrolled patients (data cutoff, October 31, 2019), 158 received ≥1 dose of diazepam nasal spray. Frequency of use was moderate in 43.7% of patients, high in 50.6% of patients, and very high in 5.7% of patients. Patients treated 3397 seizure episodes (moderate frequency, 14.2%; high frequency, 59.9%; very high frequency, 25.8%). Nasal discomfort was the most common treatment-related TEAE in all groups. No notable changes in nasal irritation or olfaction were observed. Second doses represented only 2.5%, 7.5%, and 17.2% of all doses in the moderate-, high-, and very-high-frequency groups, respectively. Overall retention rate was 82.9%, without an observed relationship to frequency of use.

SIGNIFICANCE
Frequency of dosing diazepam nasal spray had little impact on the safety/tolerability profile across a range of <2 to >5 doses/month. Effectiveness was suggested for all dosing frequencies by the high proportion of seizure clusters not treated with a second dose. These results support the utility, safety profile, and effectiveness of diazepam nasal spray across frequencies of seizure cluster burden.

diazepam
nasal spray
seizure cluster
dosing frequency
acute repetitive seizure
intranasal


Survival times with and without tube feeding in patients with dementia or psychiatric diseases in Japan.

Abstract:
BACKGROUND
It is widely supposed that there has been no evidence of increased survival in patients with advanced dementia receiving enteral tube feeding. However, more than a few studies have reported no harmful outcome from tube feeding in dementia patients compared to in patients without dementia.

METHODS
This was a retrospective study. Nine psychiatric hospitals in Okayama Prefecture participated in this survey. All inpatients fulfilling the entry criteria were evaluated. All subjects suffered from difficulty with oral intake. Attending physicians thought that the patients could not live without long-term artificial nutrition. The physicians decided whether to make use of long-term artificial nutrition between January 2012 and December 2014.

RESULTS
We evaluated 185 patients. Their mean age was 76.6 ± 11.4 years. Of all subjects, patients with probable Alzheimer's disease (n = 78) formed the biggest group, schizophrenia patients (n = 44) the second, and those with vascular dementia (n = 30) the third. The median survival times were 711 days for patients with tube feeding and 61 days for patients without tube feeding. In a comparison different types of tube feeding, median survival times were 611 days for patients with a nasogastric tube and more than 1000 days for those with a percutaneous endoscopic gastrostomy tube.

CONCLUSION
Patients with tube feeding survived longer than those without tube feeding, even among dementia patients. This study suggests that enteral nutrition for patients with dementia prolongs survival. Additionally, percutaneous endoscopic gastrostomy tube feeding may be safer than nasogastric tube feeding among patients in psychiatric hospitals.

Takayama|Keiko|K| Hirayama|Keisuke|K| Hirao|Akihiko|A| Kondo|Keiko|K| Hayashi|Hideki|H| Kadota|Koichi|K| Asaba|Hiroyuki|H| Ishizu|Hideki|H| Nakata|Kenji|K| Kurisu|Kairi|K| Oshima|Etsuko|E| Yokota|Osamu|O| Yamada|Norihito|N| Terada|Seishi|S|

tube feeding
dementia
psychiatric disease
nasogastric tube
percutaneous endoscopic gastrostomy


Local temperature and El Niño Southern Oscillation influence migration phenology of East Asian migratory waterbirds wintering in Poyang, China.

Abstract: Temperature is a critical factor influencing avian phenology, due to its direct impact on food and water availability. Most previous studies have focused on the timing of spring migration and the arrival of birds at breeding grounds along the European and American flyways; little is known about migration ecology at the wintering sites along the Asian flyways. Using linear regression models, this study investigates how local temperature variation and EI Niño Southern Oscillation (ENSO) influences the arrival and departure timing of 9 waterbird species breeding in Mongolia or Siberia and overwintering in Poyang, China from 2002 to 2013. Birds mainly arrive at Poyang in October and depart for their breeding sites in March. Out of the 9 species, 6 show a strong negative relationship between departure time and overwintering temperature in Poyang. Departure dates also show a negative association with overwintering ENSO and March ENSO for two species. Both local and large-scale climate indices show no influence on the arrival timing of waterbirds. We suggest that birds react to the annual variation of overwintering temperature: an earlier departure of waterbirds is facilitated by a warmer overwintering period and vice versa. The long-term accumulated temperature effect is more pronounced than ENSO and the short-term local temperature effect. Our findings could help quantify the potential impact of global warming on waterbirds.

ENSO
arrival and departure time
annual temperature variation
local accumulated temperature
overwintering birds


Prevention of drowning by community-based intervention: implications for low- and middle- income countries.

Abstract:
BACKGROUND
Drowning is a serious but neglected health problem in low-and middle-income countries.

OBJECTIVES
To describe the effectiveness of drowning prevention program on the reduction of drowning mortality rates in rural settings at the north of Iran, and guide its replication elsewhere.

PATIENTS AND METHODS
This interventional design included pre- and post-intervention observations in the rural area of the Caspian Sea coastline without a comparison community. Cross-sectional data were collected at pre- and post-intervention phases. Outcome evaluation was based on a four-year period (March 2005-March 2009) utilizing drowning registry data for the north of Iran.

RESULTS
The implementation program increased the rate of membership in an organization responsible for promoting safety in high risk areas near the Caspian Sea. Compared to a WHO standardized population, drowning incidence in rural areas of the study demonstrated a continuous decrease in age-specific drowning rate among the oldest victims with a gradual decline during the implementation. In the study area, the epidemiological aspects of the study population were exposed and contributing factors were highlighted.

CONCLUSIONS
This study showed that the promotion of passive interventions had a greater effect on drowning rate than that of active interventions.

Drowning
Intervention
Iran
Community Based
Prevention and Control


Collaborative learning: Elements encouraging and hindering deep approach to learning and use of elaboration strategies.

Abstract:
AIM
The purpose of this research was to investigate students' approaches to learning and use of cognitive strategies in a collaborative learning environment with team-based learning.

METHOD
In a mixed-methods study, 263 medical students from 6 different semesters answered the R-SPQ-2F Questionnaire and MSLQ's items that measure elaboration and rehearsal strategies. ANOVA was used to compare differences between semesters, and Pearson's correlation to investigate how approaches to learning, cognitive strategies, and academic achievement correlate. Focus groups elucidated which elements in the collaborative learning environment enhanced or hindered deep approach to learning or elaboration strategies and why.

RESULTS
Students took a deep approach to learning and sometimes a surface approach. They used elaboration and rehearsal strategies. First semester's students had significantly higher deep approach than fifth and sixth semesters' students. Elaboration strategies significantly correlated with final grade. Commitment to the group, case discussions, feeling challenged by teachers, and patients' visits were perceived to enhance deep approach to learning and use of elaboration strategies, while overload in course activities hindered deep approach to learning.

CONCLUSIONS
Particular elements of the learning environment triggered students to take deep approach to learning and use elaboration strategies, and this positively correlated to academic achievement.

Pires|Elda Maria Stafuzza Gonçalves|EMSG|0000-0002-8792-2870

Collaborative/peer-to-peer
education environment
general
small group


Click chemistry inspired highly facile synthesis of triazolyl ethisterone glycoconjugates.

Abstract: Numerous deoxy-azido sugars 3 were prepared by the reaction of tosyl/bromo sugars with NaN3 in dry DMF under heating condition. The 1,3-dipolar cycloaddition of deoxy-azido sugars 3 with ethisterone 4 to afford regioselective triazole-linked ethisterone glycoconjugates 5 was investigated in the presence of CuI and DIPEA in dichloromethane or CuSO4·5H2O and sodium ascorbate in aqueous medium. All the developed compounds were characterized by spectroscopic analysis (IR, (1)H &(13)C NMR, and MS spectra). Structure of triazolyl ethisterone glycoconjugate 5a has been further confirmed by its Single Crystal X-ray analysis.

Kumar|Dhananjay|D|
Mishra|Kunj B|KB|
Mishra|Bhuwan B|BB|
Mondal|Saheli|S|
Tiwari|Vinod K|VK|

Click chemistry
Ethisterone
Glycoconjugate
Carbohydrate


After-effects of self-control: The reward responsivity hypothesis.

Abstract: Exercising self-control can be phenomenologically aversive. Insofar as individuals strive to maintain a positive emotional state, one consequence of exercising self-control may thus be a temporarily tuning toward or amplification of reward-related impulses (perhaps arising to countermand the aversive feelings that stem from self-control). Reward-relevant after-effects are relatively underappreciated in self-control research. In the current paper, we review theory and research pertaining to the idea that exercising self-control increases reward responsivity. First, we review theoretical models of self-control focusing on the relationship between control systems and reward systems. Second, we review behavioral studies regarding the effects of exercising self-control on subsequent reactivity to food, money, drugs, and positive emotional images. Third, we review findings from functional neuroimaging and electroencephalographic research pertaining to the reward responsivity hypothesis. We then call for additional research to integrate how, when, and under what circumstances self-control exertion influences reward processing. Such an endeavor will help to advance research and theory on self-control by offering a more precise characterization of the dynamic interactions between control systems and reward systems.

Kelley|Nicholas J|NJ|
Finley|Anna J|AJ|
Schmeichel|Brandon J|BJ|

Self-control
Reward
Ego depletion
Mental effort
Positive affect
Self-regulation


Aberrant Functional Connectivity and Structural Atrophy in Subcortical Vascular Cognitive Impairment: Relationship with Cognitive Impairments.

Abstract: Abnormal structures in the cortical and subcortical regions have been identified in subcortical vascular cognition impairment (SVCI). However, little is known about the functional alterations in SVCI, and no study refers to the functional connectivity in the prefrontal and subcortical regions in this context. The medial prefrontal cortex (MPFC) is an important region of the executive network and default mode network, and the subcortical thalamus plays vital roles in mediating or modulating these two networks. To investigate both thalamus- and MPFC-related functional connectivity as well as its relationship with cognition in SVCI, 32 SVCI patients and 23 control individuals were administered neuropsychological assessments. They also underwent structural and functional magnetic resonance imaging scans. Voxel-based morphometry and functional connectivity analysis were performed to detect gray matter (GM) atrophy and to characterize the functional alterations in the thalamus and the MPFC. For structural data, we observed that GM atrophy was distributed in both cortical regions and subcortical areas. For functional data, we observed that the thalamus functional connectivity in SVCI was significantly decreased in several cortical regions [i.e., the orbitofrontal lobe (OFL)], which are mainly involved in executive function and memory function. However, connectivity was increased in several frontal regions (i.e., the inferior frontal gyrus), which may be induced by the compensatory recruitment of the decreased functional connectivity. The MPFC functional connectivity was also decreased in executive- and memory-related regions (i.e., the anterior cingulate cortex) along with a motor region (i.e., the supplementary motor area). In addition, the cognitive performance was closely correlated with functional connectivity between the left thalamus and the left OFL in SVCI. The present study, thus, provides evidence for an association between structural and functional alterations, and sheds light on the underlying neural mechanisms of executive dysfunction in SVCI.

Zhou|Xia|X| Hu|Xiaopeng|X| Zhang|Chao|C| Wang|Haibao|H| Zhu|Xiaoqun|X| Xu|Liyan|L| Sun|Zhongwu|Z| Yu|Yongqiang|Y|

functional connectivity
vascular cognition impairment
MPFC
thalamus
gray matter atrophy
resting-state fMRI


Boosting in vitro cartilage tissue engineering through the fabrication of polycaprolactone-gelatin 3D scaffolds with specific depth-dependent fiber alignments and mechanical stimulation.

Abstract: Due to the limited self-healing ability of natural cartilage, several tissue engineering strategies have been explored to develop functional replacements. Still, most of these approaches do not attempt to recreate in vitro the anisotropic organization of its extracellular matrix, which is essential for a suitable load-bearing function. In this work, different depth-dependent alignments of polycaprolactone-gelatin electrospun fibers were assembled into three-dimensional scaffold architectures to assess variations on chondrocyte response under static, unconfined compressed and perfused culture conditions. The in vitro results confirmed that not only the 3D scaffolds specific depth-dependent fiber alignments potentiated chondrocyte proliferation and migration towards the fibrous systems, but also the mechanical stimulation protocols applied were able to enhance significantly cell metabolic activity and extracellular matrix deposition, respectively.

Semitela|Ângela|Â|
Girão|André F|AF|
Fernandes|Carla|C|
Ramalho|Gonçalo|G|
Pinto|Susana C|SC|
Completo|António|A|
Marques|Paula A A P|PAAP|

Cartilage tissue engineering
Mechanical stimulation
Depth-dependent properties
Electrospinning


Development of a Resource Impact Model for Clinics Treating Pre-Operative Iron Deficiency Anemia in Ireland.

Abstract:
INTRODUCTION
Intravenous (IV) iron is typically the preferred treatment for patients with iron deficiency anemia (IDA) who cannot tolerate or absorb oral iron, or who require fast replenishment of iron stores pre-operatively. Several IV iron formulations are available with different dosing characteristics affecting infusion speed and maximum dose. The aim was to develop a resource impact model to calculate the cost of establishing an IV iron clinic and model resource impact of different IV irons to inform clinicians and service providers implementing innovative pre-operative IV iron services in Ireland.

METHODS
A resource impact tool was developed to model resource utilization and IDA treatment costs. Two fast-administration, high-dose formulations of IV iron are available in Ireland: iron isomaltoside 1000/ferric derisomaltose (IIM) and ferric carboxymaltose (FCM). The tool modeled clinic throughput based on their different dosing characteristics in a specific IDA population, capturing fixed overheads, variable costs, clinic income from private and publicly-funded patients, and savings associated with IV iron.

RESULTS
Based on a 70:30 split between public and private patients in a new pre-operative service with capacity for 12 infusion slots weekly, IIM would facilitate correction of iron deficits in 474 patients annually, resulting in a net annual clinic balance of €42,736 on income of €159,887 and net costs of €117,151. FCM would facilitate treatment of 353 patients, resulting in a net annual clinic balance of €36,327 on income of €116,050 and costs of €79,722, a difference of €6408 and 121 patients treated in favor of using IIM over FCM.

CONCLUSION
Based on this provider-perspective analysis, IIM would maximize clinic throughput relative to other IV iron formulations, allowing clinicians in Ireland to optimize their current service provision and expenditure, and model the impact of introducing IV iron clinics for pre-operative patients with IDA.

D061605:Administration, Intravenous
D000554:Ambulatory Care Facilities
D018798:Anemia, Iron-Deficiency
D003365:Costs and Cost Analysis
D004187:Disaccharides
D005290:Ferric Compounds
D006295:Health Resources
D006801:Humans
D007494:Ireland
D008320:Maltose
D018803:Models, Economic
D011300:Preoperative Care

Iron
Iron deficiency anemia
Ireland
Intravenous
Administration
Costs and cost analysis
Health economics
Hematology