Fragmented Dosing of β-alanine Induces A Body Weight-Independent Pharmacokinetic Response.

Abstract: Personalised dosing of performance-enhancing food supplements is a hot topic. β-alanine is currently dosed using a fixed dose; however, evidence suggests that this might favour light compared to heavy subjects. A weight-relative dose seems to reverse this problem. In the present study, a novel dosing strategy was tested. A fragmented dose, composed of a fixed fragment of 800 mg and a weight-relative fragment of 10 mg/kg body weight, was compared to a fixed dose of 1600 mg and a weight-relative dose of 20 mg/kg body weight in a cohort of 20 subjects with a body weight ranging 48-139 kg (79.9 ± 24.4 kg). The results show that, following a fragmented dose, the influence of body weight on the pharmacokinetic response (iAUC) over a 210 min period was absent (r = -0.168; p = 0.478), in contrast to the fixed or weight-relative dose. The pharmacokinetic response also seemed more homogenous (CV% = 26%) following a fragmented dose compared to the fixed (33%) and the weight-relative dose (31%). The primary advantage of the easy-to-calculate fragmented dosing strategy is that it does not systematically favour or impair a certain weight group. Thorough dosage studies are lacking in the current field of sports and food supplements, therefore similar considerations can be made towards other (ergogenic) food supplements.

food supplement
ergogenic
beta-alanine
carnosine
personalised nutrition


Bridging the gap between clinical practice and public health: Using EHR data to assess trends in the seasonality of blood-pressure control.

Abstract: Electronic health records (EHRs) provide timely access to millions of patient data records while limiting errors associated with manual data extraction. To demonstrate these advantages of EHRs to public health practice, we examine the ability of a EHR calculated blood-pressure (BP) measure to replicate seasonal variation as reported by prior studies that used manual data extraction. Our sample included 609 primary-care practices in New York City. BP control among hypertensives was defined as systolic blood pressure of 140 or less and diastolic blood pressure of 90 or less (BP < 140/90 mm Hg). An innovative query-distribution system was used to extract monthly BP control values from the EHRs of adult patients diagnosed with hypertension over a 25-month period. Generalized estimating equations were used to compare the association between seasonal temperature variations and BP control rates at the practice level, while adjusting for known demographic factors (age, gender), comorbid diseases (diabetes) associated with blood pressure, and months since EHR implementation. BP control rates increased gradually from the spring months to peak summer months before declining in the fall months. In addition to seasonal variation, the adjusted model showed that a 1% increase in patients with a diabetic comorbidity is associated with an increase of 3% (OR 1.03; CI 1.028-1.032) on the BP measure. Our findings identified cyclic trends in BP control and highlighted greater association with increased proportion of diabetic patients, therefore confirming the ability of the EHR as a tool for measuring population health outcomes.

Amoah|Aurora O|AO|
Angell|Sonia Y|SY|
Byrnes-Enoch|Hannah|H|
Amirfar|Sam|S|
Maa|Phoenix|P|
Wang|Jason J|JJ|

Public health
Electronic health records
Seasonal variation
Population health
Blood pressure control
Chronic disease
Healthcare quality
Primary care
Quality measures


Randomised prior feedback modulates neural signals of outcome monitoring.

Abstract: Substantial evidence indicates that decision outcomes are typically evaluated relative to expectations learned from relatively long sequences of previous outcomes. This mechanism is thought to play a key role in general learning and adaptation processes but relatively little is known about the determinants of outcome evaluation when the capacity to learn from series of prior events is difficult or impossible. To investigate this issue, we examined how the feedback-related negativity (FRN) is modulated by information briefly presented before outcome evaluation. The FRN is a brain potential time-locked to the delivery of decision feedback and it is widely thought to be sensitive to prior expectations. We conducted a multi-trial gambling task in which outcomes at each trial were fully randomised to minimise the capacity to learn from long sequences of prior outcomes. Event-related potentials for outcomes (Win/Loss) in the current trial (Outcomet) were separated according to the type of outcomes that occurred in the preceding two trials (Outcomet-1 and Outcomet-2). We found that FRN voltage was more positive during the processing of win feedback when it was preceded by wins at Outcomet-1 compared to win feedback preceded by losses at Outcomet-1. However, no influence of preceding outcomes was found on FRN activity relative to the processing of loss feedback. We also found no effects of Outcomet-2 on FRN amplitude relative to current feedback. Additional analyses indicated that this effect was largest for trials in which participants selected a decision different to the gamble chosen in the previous trial. These findings are inconsistent with models that solely relate the FRN to prediction error computation. Instead, our results suggest that if stable predictions about future events are weak or non-existent, then outcome processing can be determined by affective systems. More specifically, our results indicate that the FRN is likely to reflect the activity of positive affective systems in these contexts. Importantly, our findings indicate that a multifactorial explanation of the nature of the FRN is necessary and such an account must incorporate affective and motivational factors in outcome processing.

Mushtaq|Faisal|F|
Wilkie|Richard M|RM|
Mon-Williams|Mark A|MA|
Schaefer|Alexandre|A|

Monitoring
Feedback-related negativity
Affective priming
Reward prediction error
Salience
Short-term expectations
Uncertainty


Tissue-specific transcriptomics in the field cricket Teleogryllus oceanicus.

Abstract: Field crickets (family Gryllidae) frequently are used in studies of behavioral genetics, sexual selection, and sexual conflict, but there have been no studies of transcriptomic differences among different tissue types. We evaluated transcriptome variation among testis, accessory gland, and the remaining whole-body preparations from males of the field cricket, Teleogryllus oceanicus. Non-normalized cDNA libraries from each tissue were sequenced on the Roche 454 platform, and a master assembly was constructed using testis, accessory gland, and whole-body preparations. A total of 940,200 reads were assembled into 41,962 contigs, to which 36,856 singletons (reads not assembled into a contig) were added to provide a total of 78,818 sequences used in annotation analysis. A total of 59,072 sequences (75%) were unique to one of the three tissues. Testis tissue had the greatest proportion of tissue-specific sequences (62.6%), followed by general body (56.43%) and accessory gland tissue (44.16%). We tested the hypothesis that tissues expressing gene products expected to evolve rapidly as a result of sexual selection--testis and accessory gland--would yield a smaller proportion of BLASTx matches to homologous genes in the model organism Drosophila melanogaster compared with whole-body tissue. Uniquely expressed sequences in both testis and accessory gland showed a significantly lower rate of matching to annotated D. melanogaster genes compared with those from general body tissue. These results correspond with empirical evidence that genes expressed in testis and accessory gland tissue are rapidly evolving targets of selection.

Bailey|Nathan W|NW|
Veltsos|Paris|P|
Tan|Yew-Foon|YF|
Millar|A Harvey|AH|
Ritchie|Michael G|MG|
Simmons|Leigh W|LW|

tissue-specific transcriptome
field cricket
Teleogryllus oceanicus
gryllid
reference transcriptome


Glycine N-methyltransferase expression in the hippocampus and its role in neurogenesis and cognitive performance.

Abstract: The hippocampus is a brain area characterized by its high plasticity, observed at all levels of organization: molecular, synaptic, and cellular, the latter referring to the capacity of neural precursors within the hippocampus to give rise to new neurons throughout life. Recent findings suggest that promoter methylation is a plastic process subjected to regulation, and this plasticity seems to be particularly important for hippocampal neurogenesis. We have detected the enzyme GNMT (a liver metabolic enzyme) in the hippocampus. GNMT regulates intracellular levels of SAMe, which is a universal methyl donor implied in almost all methylation reactions and, thus, of prime importance for DNA methylation. In addition, we show that deficiency of this enzyme in mice (Gnmt-/-) results in high SAMe levels within the hippocampus, reduced neurogenic capacity, and spatial learning and memory impairment. In vitro, SAMe inhibited neural precursor cell division in a concentration-dependent manner, but only when proliferation signals were triggered by bFGF. Indeed, SAMe inhibited the bFGF-stimulated MAP kinase signaling cascade, resulting in decreased cyclin E expression. These results suggest that alterations in the concentration of SAMe impair neurogenesis and contribute to cognitive decline.

Carrasco|Manuel|M|
Rabaneda|Luis G|LG|
Murillo-Carretero|Maribel|M|
Ortega-Martínez|Sylvia|S|
Martínez-Chantar|María L|ML|
Woodhoo|Ashwin|A|
Luka|Zigmund|Z|
Wagner|Conrad|C|
Lu|Shelly C|SC|
Mato|José M|JM|
Micó|Juan A|JA|
Castro|Carmen|C|

D000592:Amino Acid Metabolism, Inborn Errors

glycine N-methyltransferase
neurogenesis
learning
memory
S-adenosylmethionine
neural progenitor cells


Impact of sulfadiazine on performance and microbial community of a sequencing batch biofilm reactor treating synthetic mariculture wastewater.

Abstract: The impact of sulfadiazine on the performance, microbial activity and microbial community of a sequencing batch biofilm reactor (SBBR) were evaluated in treating mariculture wastewater due to the application of sulfadiazine as an antibiotic in mariculture. The COD and nitrogen removals kept stable at 0-6mg/L sulfadiazine and were inhibited at 10-35mg/L sulfadiazine. The microbial activities related to organic matter and nitrogen removals reduced with an increase in sulfadiazine concentration. The presence of sulfadiazine could affect the production and chemical composition of loosely bound extracellular polymeric substances (LB-EPS) and tightly bound EPS (TB-EPS) in the biofilm. High-throughput sequencing demonstrated that sulfadiazine could impact on the microbial richness and diversity of SBBR treating mariculture wastewater. The relative abundances of Nitrosomonas, Nitrospira, Paracoccus, Hyphomicrobium, Rhodanobacter, Thauera and Steroidobacter decreased with an increase in sulfadiazine concentration, indicating that the presence of sulfadiazine decreased the relative abundance of some nitrifying and denitrifying bacteria.

Li|Zhiwei|Z| Chang|Qingbo|Q| Li|Shanshan|S| Gao|Mengchun|M| She|Zonglian|Z| Guo|Liang|L| Zhao|Yangguo|Y| Jin|Chunji|C| Zheng|Dong|D| Xu|Qiaoyan|Q|

Sulfadiazine
Microbial community
Mariculture wastewater
SBBR
Extracellular polymeric substances


Embarking on a Journey of Discovery: Developing Transitional Skill Sets through a Scholarly Concentration Program.

Abstract:
PROBLEM
Medical student participation in research enhances appreciation of the scientific literature and the conduct of investigation, and may lead to an interest in academic medicine. Independent medical student research offers frequently overlooked opportunities to develop and assess professional practice abilities, including project design and implementation, interprofessional team communication, and time management. These skills, useful to physicians, are often challenging for medical students to master as they transition into clinical careers. To address this challenge, we designed and embedded interventional modalities into a highly mentored and longitudinal scholarly concentration component of the curriculum.

INTERVENTION
The Embark scholarly concentration program incorporates traditional research training with the development of professional practice skills essential for transitioning to clinical practice. The program includes individualized and just-in-time components enabling student access to information and feedback specific to their projects and development of professional practice skills.

CONTEXT
The Embark program is a required longitudinal component of the Oakland University William Beaumont School of Medicine undergraduate medical curriculum. The Embark program consists of courses that inform and facilitate a required longitudinal independent research project.

OUTCOME
A retrospective evaluation of the Embark program's success with development of professional practice skills through the lens of both faculty and student perceptions included analysis of project records and course evaluation feedback. Evaluation of individual student development of transitional skill ability is possible through both quantitative and qualitative analysis of data collected from student project records. More than 80% of course evaluation commentary on strengths of the program addressed activities related to professional practice skills. To systematize the evaluation of these data sources, we have piloted a framework, iSAIL, designed to assess student development in these skills during the planning and conduct of a research project.

LESSONS LEARNED
By developing professional practice skills in the context of a scholarly concentration program, medical students can build a foundation for future engagement in research while they develop skills to overcome challenges that they are likely to encounter in their clinical careers. Modalities designed to evaluate individualized student development of professional practice skills through research participation define program successes and may lead to the identification of additional resources needed by students. By offering medical students opportunities to develop professional practice skills within the protected environment of an independent research project, this scholarly concentration program provides a valuable opportunity to influence the early development of skills necessary throughout their clinical careers.

D000073819:Self-Directed Learning as Topic

transitional skills
scholarly concentration
Medical student
professional skills
self-directed learning


HIV/AIDS-Related Knowledge and Behaviors Among Most-at-Risk Populations in Vietnam.

Abstract: The U.S. President's Emergency Plan for AIDS Relief (PEPFAR) has supported the Vietnamese Ministry of Health (MOH) in implementing behavior change strategies to slow the HIV epidemic. These programs target commercial sex workers (CSW), injection drug users (IDU), and men who have sex with men (MSM). Using data from a program evaluation to assess effectiveness of the PEPFAR intervention, we conducted a sub-analysis of HIV/AIDS knowledge, sexual behaviors, and injection drug risk behaviors among 2,199 Vietnamese respondents, including those reporting recent contact with an outreach worker and those who did not report contact. We found overall high levels of HIV/AIDS knowledge, low rates of needle sharing, and moderate to high rates of inconsistent condom use. Average knowledge scores of IDU were significantly higher than non-IDU for antiretroviral treatment knowledge, while MSM had significantly less knowledge of treatment compared to non-MSM. HIV/AIDS-related knowledge was not significantly associated with needle-sharing practices. Knowledge was modestly but significantly associated with more consistent use of condoms with primary and commercial sex partners, even after controlling for contact with an outreach worker. Contact with an outreach worker was also an independent predictor of more consistent condom use. Outreach programs appear to play a meaningful role in changing sexual behavior, though the effect of outreach on IDU risk behaviors was less clear. More research is needed to understand the relationship between outreach programs and skill development, motivation, and use of referral services by most-at-risk populations in Vietnam.

Vian|Taryn|T|
Semrau|Katherine|K|
Hamer|Davidson H|DH|
Loan|Le Thi Thanh|le TT|
Sabin|Lora L|LL|

Vietnam
commercial sex workers
injection drug users
men who have sex with men
HIV/AIDS
health communications
most-at-risk populations.
sex behavior


Properties of Surface Heating Textile for Functional Warm Clothing Based on a Composite Heating Element with a Positive Temperature Coefficient.

Abstract: A high-stretch positive temperature coefficient (PTC) surface heating textile (PTC-SHT) was fabricated using a composite of PTC powder and multiwall carbon nanotubes (MWCNTs). The PTC-SHT (heating area = 100 × 100 mm2) was produced by screen-printing the PTC-MWCNT composite paste onto a high-stretch textile with embroidered electrodes. Overall, the temperature increased to 56.1 °C with a power consumption of 5 W over 7 min. Subsequently, the surface temperature of the PTC-SHT remained constant despite the continued decrease in power consumption. This indicated that heating was accompanied by an increase in resistance of the PTC-SHT, which is typical of this process-i.e., heating to a constant temperature under a constant voltage over an extended period of time. In addition, 4.63 W power was required to heat the PTC-SHT surface from an external temperature of 5 to 45 °C in 10 min, after which stable low-temperature heat generation behavior was observed at a constant temperature of 50 °C, which was maintained over 40 min. In contrast, negative temperature coefficient (NTC) behavior has been observed in an NTC-SHT consisting of only MWCNTs, where a slow heating rate in the initial stage of power application and a continuous increase in surface temperature and power consumption were noted. The PTC-SHT consumed less power for heat generation than the NTC-SHT and exhibited rapid heating behavior in the initial stage of power application. The heat generation characteristics of the PTC-SHT were maintained at 95% after 100,000 cycles of 20% stretch-contraction testing, and the heating temperature remained uniformly distributed within ± 2 °C across the entire heating element. These findings demonstrated that an SHT with PTC characteristics is highly suitable for functional warm clothing applications that require low power consumption, rapid heating, stable warmth, and high durability.

Choi|Han Na|HN|
Jee|Seung Hyun|SH|
Ko|Jaehwan|J|
Kim|Dong Joo|DJ|0000-0001-5013-4005
Kim|Sun Hee|SH|

heating textile
CNT
IC joule heater
heated clothing
heating performance
surface heating elements


Cord Lining Mesenchymal Stem Cells Have a Modest Positive Effect on Angiogenesis in Hindlimb Ischemia.

Abstract: Purpose: We investigated the use of human Cord Lining Mesenchymal Stem Cells (CL-MSCs) (US Patent number 9,737,568), in a rabbit hindlimb ischemia model, and evaluated their potential in stimulating neovascularization. Allogenic human CL- MSCs could potentially be used to treat patients with lower limb ischemia and non-healing wounds. Methods: Twenty rabbits were divided into two separate groups. We created a hindlimb ischemia model surgically. At 21 and 49 days post-operatively, animals in the treatment group were injected with CL-MSCs (500,000 cells per 0.2 ml on each site) at 10 different sites (Quadriceps- 4 sites, Hamstrings- 4 sites and Calf--2 sites) in the hindlimb muscles. The control group received only saline injection to the corresponding sites at the same time point as the treatment group. We then evaluated the effects of treatment on neovascularization by angiography, laser doppler perfusion imaging, as well as by histology. We evaluated the tissue samples for any signs of local immune reaction to the cell implantation. We also observed the rabbit clinically for any adverse effects after treatment. Results: We found a higher number of CD31 positive cells in the treatment group, with a greater number of capillaries found in the treated muscles. The Rectus Femoris demonstrated a median vessel count/muscle fiber of 0.121 for the treatment group, compared to 0.076 in the control group (median difference 0.04; 95% CI 0.001-0.11; p = 0.041). The Gastrocnemius demonstrated a median vessel count/muscle fiber of 0.175 for the treatment group, compared to 0.089 in the control group (median difference 0.087; 95% CI -0.006 to 0.234; p = 0.07). Blood perfusion quantification through Laser Doppler Perfusion Imaging (LDPI) also demonstrated a non-statistically significant increase in perfusion in favor of the treatment group. CL-MSCs demonstrated no toxicity associated morbidity and minimal local immune reaction to implantation. Conclusion: CL-MSCs have a positive effect on angiogenesis in a rabbit hindlimb ischemia model. This preliminary data is encouraging and paves the way for future large animal studies or for clinical trials.

Chua|Kenon|K|
Lim|Fui Ping|FP|
Lee|Victor Kwan Min|VKM|
Phan|Toan Thang|TT|
Tai|Bee Choo|BC|
Tan|Yih Kai|YK|

mesenchymal stem cell
stem cell
angiogenesis
hindlimb ischemia
cell therapy
critical limb ischemia
peripheral arterial disease


Impact of de novo donor-specific HLA antibodies detected by Luminex solid-phase assay after transplantation in a group of 88 consecutive living-donor renal transplantations.

Abstract: De novo donor-specific HLA antibodies (DSA) after renal transplantation are known to be correlated with poor graft outcome and the development of acute and chronic rejection. Currently, data for the influence of de novo DSA in patient cohorts including only living-donor renal transplantations (LDRT) are limited. A consecutive cohort of 88 LDRT was tested for the occurrence of de novo DSA by utilizing the highly sensitive Luminex solid-phase assay for antibody detection. Data were analyzed for risk factors for de novo DSA development and correlated with acute rejection (AR) and graft function. Patients with de novo DSA [31 (35%)] showed a trend for inferior graft function [mean creatinine change (mg/dL/year) after the first year: 0.15 DSA (+) vs. 0.02 DSA (-) (P = 0.10)] and a higher rate of AR episodes, especially in case of de novo DSA of both class I and II [6 (55%), (P = 0.05)]. Antibody-mediated rejection (AMR) appeared in five patients and was significantly correlated with de novo DSA (P = 0.05). Monitoring for de novo DSA after LDRT may help to identify patients at risk of declining renal function. Especially patients with simultaneous presence of de novo DSA class I and class II are at a high risk to suffer AR episodes.

Dieplinger|Georg|G|
Ditt|Vanessa|V|
Arns|Wolfgang|W|
Huppertz|Andrea|A|
Kisner|Tuelay|T|
Hellmich|Martin|M|
Bauerfeind|Ursula|U|
Stippel|Dirk L|DL|

D015395:Histocompatibility Antigens Class I

D000949:Histocompatibility Antigens Class II


Y-STR Haplogroup Diversity in the Jat Population Reveals Several Different Ancient Origins.

Abstract: The Jats represent a large ethnic community that has inhabited the northwest region of India and Pakistan for several thousand years. It is estimated the community has a population of over 123 million people. Many historians and academics have asserted that the Jats are descendants of Aryans, Scythians, or other ancient people that arrived and lived in northern India at one time. Essentially, the specific origin of these people has remained a matter of contention for a long time. This study demonstrated that the origins of Jats can be clarified by identifying their Y-chromosome haplogroups and tracing their genetic markers on the Y-DNA haplogroup tree. A sample of 302 Y-chromosome haplotypes of Jats in India and Pakistan was analyzed. The results showed that the sample population had several different lines of ancestry and emerged from at least nine different geographical regions of the world. It also became evident that the Jats did not have a unique set of genes, but shared an underlying genetic unity with several other ethnic communities in the Indian subcontinent. A startling new assessment of the genetic ancient origins of these people was revealed with DNA science.

Y-STR haplogroups Jats India Pakistan Y-chromosome Y-DNA haplotypes


The impact of trans-arterial embolization on the result of chemoradiotherapy in oral cavity cancer.

Abstract: Objectives: Evaluation of the hemostatic effect of trans-arterial embolization on patients with advanced oral cavity cancer who had bleeding complications while undergoing definitive concurrent chemoradiotherapy (CCRT). Additionally, assess the effect of trans-arterial embolization on treatment response following concurrent chemoradiotherapy, as well as overall survival (OS) and progression-free survival (PFS) in the group of patients following the intervention.Method: From September 2018-June 2021, a retrospective descriptive study was conducted on 16 patients with inoperable, locally advanced oral cavity cancer who received definitive concurrent chemoradiotherapy, experienced acute bleeding complications, and received selective intravascular intervention with various embolization materials at Vietnam National Cancer Hospital.Results: After selective embolization, 16/16 patients ceased bleeding; 1 patient re-bled for the second time after 3 weeks. The average duration of chemoradiotherapy interruption due to intervention was 6.7 days. After CCRT, 15/16 (93.75%) patients achieved a response, with 9/16 (56.25%) patients achieving a complete response. The median OS was 14 months (range, 3-26 months), and the median PFS was 10 months (range, 3-20 months). There were no significant complications, particularly neurological side effects.ConclusionsTumor bleeding is a common and serious complication of CCRT treatment in patients with locally advanced oral cavity cancer. Embolization is a safe and effective method of controlling acute bleeding that has no adverse effect on the outcome of definitive concurrent chemoradiotherapy.

trans-arterial embolization
advanced oral cavity cancer
acute bleeding


Optogenetic tools for manipulation of cyclic nucleotides functionally coupled to cyclic nucleotide-gated channels.

Abstract:
BACKGROUND AND PURPOSE
The cyclic nucleotides cAMP and cGMP are ubiquitous second messengers regulating numerous biological processes. Malfunctional cNMP signalling is linked to diseases and thus is an important target in pharmaceutical research. The existing optogenetic toolbox in Caenorhabditis elegans is restricted to soluble adenylyl cyclases, the membrane-bound Blastocladiella emersonii CyclOp and hyperpolarizing rhodopsins; yet missing are membrane-bound photoactivatable adenylyl cyclases and hyperpolarizers based on K+ currents.

EXPERIMENTAL APPROACH
For the characterization of photoactivatable nucleotidyl cyclases, we expressed the proteins alone or in combination with cyclic nucleotide-gated channels in muscle cells and cholinergic motor neurons. To investigate the extent of optogenetic cNMP production and the ability of the systems to depolarize or hyperpolarize cells, we performed behavioural analyses, measured cNMP content in vitro, and compared in vivo expression levels.

KEY RESULTS
We implemented Catenaria CyclOp as a new tool for cGMP production, allowing fine-control of cGMP levels. We established photoactivatable membrane-bound adenylyl cyclases, based on mutated versions ("A-2x") of Blastocladiella and Catenaria ("Be," "Ca") CyclOp, as N-terminal YFP fusions, enabling more efficient and specific cAMP signalling compared to soluble bPAC, despite lower overall cAMP production. For hyperpolarization of excitable cells by two-component optogenetics, we introduced the cAMP-gated K+ -channel SthK from Spirochaeta thermophila and combined it with bPAC, BeCyclOp(A-2x), or YFP-BeCyclOp(A-2x). As an alternative, we implemented the B. emersonii cGMP-gated K+ -channel BeCNG1 together with BeCyclOp.

CONCLUSION AND IMPLICATIONS
We established a comprehensive suite of optogenetic tools for cNMP manipulation, applicable in many cell types, including sensory neurons, and for potent hyperpolarization.

optogenetics
cyclic nucleotide-gated channels
Caenorhabditis elegans
adenylyl cyclases
rhodopsin
guanylyl cyclases
neuromuscular system


A protocol for developing, disseminating, and implementing a core outcome set (COS) for childbirth pelvic floor trauma research.

Abstract:
BACKGROUND
More than 85% of women sustain different degrees of trauma during vaginal birth. Randomized controlled trials on childbirth pelvic floor trauma have reported a wide range of outcomes and used different outcome measures. This variation restricts effective data synthesis, impairing the ability of research to inform clinical practice. The development and use of a core outcome set (COS) for childbirth pelvic floor trauma aims to ensure consistent use of outcome measures and reporting of outcomes.

METHODS
An international steering group, within CHORUS, an International Collaboration for Harmonising Outcomes, Research and Standards in Urogynaecology and Women's Health, including academic community members, researchers, healthcare professionals, policy makers and women with childbirth pelvic floor trauma will lead the development of this COS. Relevant outcome parameters will be identified through comprehensive literature reviews. The selected outcomes will be entered into an international, multi-perspective online Delphi survey. Subsequently and based on the results of the Delphi surveys consensus will be sought on 'core' outcomes.

DISCUSSION
Dissemination and implementation of the resulting COS within an international context will be supported and promoted. Embedding the COS for childbirth pelvic floor trauma within future clinical trials, systematic reviews, and clinical practice guidelines is expected to enrich opportunities for comparison of future clinical trials and allow better synthesis of outcomes, and will enhance mother and child care. The infrastructure created by developing a COS for childbirth pelvic floor trauma could be leveraged in other settings, for example, advancing research priorities and clinical practice guideline development.

D032921:Consensus
D036861:Delivery, Obstetric
D003697:Delphi Technique
D005260:Female
D006801:Humans
D017063:Outcome Assessment, Health Care
D017773:Pelvic Floor
D059952:Pelvic Floor Disorders
D011247:Pregnancy
D012107:Research Design
D000073597:Stakeholder Participation
D016896:Treatment Outcome

Core outcome measures in effectiveness trials (COMET)

International collaboration for Harmonising outcomes (CHORUS)

Recommendations for interventional trials (SPIRIT)


Annual glycemic variations and risk of cancer among Chinese patients with type 2 diabetes mellitus: A population-based cohort study in Shanghai.

Abstract:
BACKGROUND
Long-term glycemic variation in diabetes patients may have contributed to cancer incidence.

AIM
In this study we aimed at the association between annual glycemic variation and the risk of cancer in Chinese patients with type 2 diabetes mellitus (T2DM).

METHODS
Subjects of this study were from an established population-based cohort of T2DM patients in Minhang District of Shanghai, China. Incident cancer were obtained from the Shanghai Cancer Registry. Glycemic variation was evaluated using the annual fasting glucose coefficient of variation (FG-CV), which was used as a time-dependent variable in a Cox regression model to estimate the associations with the cancer risk. Restricted cubic splines were used to explore potential non-linear associations.

RESULTS
A total of 2,140 incident cancers (1100 men and 1040 women) were identified from the 46,202 diabetes patients during 12-year follow-up. The annual FG-CV remained significantly associated with an increased risk of cancer, even after adjusting for the annual mean FG level. A significant non-linear association was found in male T2DM patients, and a significant linear association in female patients.

CONCLUSIONS
The positive association of the annual FG-CV with the risk of cancer in T2DM patients indicate the importance to stabilize the FG level.

Xu|Huilin|H| Zhang|Fen|F| Xu|Wanghong|W| Li|Jun|J| Zhu|Jingjing|J| Zhang|Minlu|M| Wu|Zhenyu|Z| Qin|Guoyou|G|

Glycemic variation
Cancer
Type 2 diabetes mellitus
Fasting glucose
Time-dependent Cox regression model


SARS-CoV-2 -RNA persists longer in faecal sample as compared to nasal and throat swab samples of COVID-19 patients'; an observational study.

Abstract: The route of transmission of Novel SARS-CoV-2 virus is ambiguous. In this regard we planned a study to find out SARS-CoV-RNA shedding in various clinical samples of 9 COVID-19 positive patients. SARS-CoV-RNA was detected in nasal swab (NS), throat swab (TS) and faecal sample but was not detected in serum and urine samples. We also report that SARS-CoV-2-RNA persisted in faeces for >20 days. Persistence of faecal RNA might impose challenge in infection control and the disease may spread to household contacts if discharged. Perineal cleaning and hygiene may be advised at the time of vaginal delivery.

Prakash|Shantanu|S|
Shukla|Suruchi|S|
Mishra|Hricha|H|
Prakash|Om|O|
Khan|Danish N|DN|
Pandey|Ajay|A|
Reddy|D Himanshu|DH|
Jain|Amita|A|

Clinical samples
Perineal cleaning
Clinical features
Faecal RNA persistence
SARS CoV-2


Anterior segment reconstruction with artificial iris and Descemet membrane endothelial keratoplasty: a staged surgical approach.

Abstract:
PURPOSE
To describe a surgical approach that involves anterior segment reconstruction with CustomFlex Artificial Iris (CAI; HumanOptics, Erlangen, Germany) followed by Descemet membrane endothelial keratoplasty (DMEK) in complex eyes with corneal decompensation.

METHODS
Restrospective case series of eyes that underwent anterior segment restoration involving (1) synechiolysis of peripheral anterior synechiae and excision of iris remnants, (2) securing a well-fixated posterior chamber intraocular lens and (3) suture-fixated or capsular bag placement of CAI. All eyes then underwent DMEK using a pull-through technique with the DMEK EndoGlide (Network Medical Products, Ripon, UK). Main outcomes were successful anterior segment restoration and corneal clarity with central corneal thickness (CCT).

RESULTS
Five eyes of five patients (median age 61 years, range 27-69 years; 60% female) underwent anterior segment reconstruction with CAI implantation (4 suture-fixated), followed by successful DMEK surgery (median 2 months later, range 1-5 months). There were no major intraoperative complications or primary graft failure, with one peripheral graft detachment that underwent a successful re-bubble at 1 week. All eyes had stable CAI implants and DMEK grafts remained clear at last follow-up with reduction in mean central corneal thickness (preoperative: 658±86 µm vs postoperative: 470±33 µm, p=0.005).

CONCLUSION
This pilot study highlights a feasible approach of initial anterior segment reconstruction with CAI implantation, prior to DMEK, in eyes with significant anterior segment abnormalities such as iris damage or extensive peripheral anterior synechiae and corneal decompensation.


The Mitochondrial Complex(I)ty of Cancer.

Abstract: Recent evidence highlights that the cancer cell energy requirements vary greatly from normal cells and that cancer cells exhibit different metabolic phenotypes with variable participation of both glycolysis and oxidative phosphorylation. NADH-ubiquinone oxidoreductase (Complex I) is the largest complex of the mitochondrial electron transport chain and contributes about 40% of the proton motive force required for mitochondrial ATP synthesis. In addition, Complex I plays an essential role in biosynthesis and redox control during proliferation, resistance to cell death, and metastasis of cancer cells. Although knowledge about the structure and assembly of Complex I is increasing, information about the role of Complex I subunits in tumorigenesis is scarce and contradictory. Several small molecule inhibitors of Complex I have been described as selective anticancer agents; however, pharmacologic and genetic interventions on Complex I have also shown pro-tumorigenic actions, involving different cellular signaling. Here, we discuss the role of Complex I in tumorigenesis, focusing on the specific participation of Complex I subunits in proliferation and metastasis of cancer cells.

Urra|Félix A|FA|
Muñoz|Felipe|F|
Lovy|Alenka|A|
Cárdenas|César|C|

cancer cells
electron transport chain
metastasis
anticancer agents
mitochondrial respiration


Surgical Pearl on Reconstructing Surgical Defects of the Nasal Tip.

Abstract: Repairing surgical defects of the nasal tip is challenging, mainly because of the lack of freely mobile skin available peripherally. The Peng flap is a one-stage cutaneous flap that circumvents this difficulty by recruiting skin from the nasal dorsum and sidewall regions. The design produces a tridimensional shape perfectly adapted to the configuration of the nasal tip and allows for an inconspicuous closure of the defect. We present three examples of full-thickness skin defects involving the nasal tip, reconstructed using a modified version of the Peng flap, and present the experience at our department with this surgical technique.

César|Artur|A| Barros|Ana|A| Santos|Paulo|P| Azevedo|Filomena|F|


Caries-risk assessment with a chairside optical spectroscopic sensor by monitoring bacterial-mediated acidogenic-profile of saliva in children.

Abstract:
OBJECTIVE
This study aimed to evaluate the ability of an optical spectroscopic sensor (OSS) to monitor bacterial-mediated acidogenic-profile of saliva resulting from bacteria-sucrose interaction.

MATERIALS AND METHODS
Stage-1, characterization experiments were conducted to standardize the OSS. Stage-2 clinical experiments were carried out on stimulated saliva samples from 70 children of age-group 1-12 years. The bacterial-mediated acidogenic-profile of saliva mixed with sucrose was monitored using the OSS for 180 minutes.

RESULTS
The clinical patients were categorized based on the dmfs score as caries-active, caries-inactive and caries-free. The bacterial-mediated acidogenic-profile measured in terms of t1/2 monitored using the OSS was significantly different between the caries-free and caries-active (P<0.05); and caries-free and caries-inactive groups (P<0.005).

CONCLUSIONS
The significant correlation of the acidogenic-profile determined using the OSS and the caries-status highlighted the OSS as a sensitive and rapid chairside tool for the quantification of the acidogenic-profile of saliva that could help in monitoring the caries-risk in children.

Shrestha|Annie|A| Mohamed-Tahir|Ma|M| Hegde|Jayshree|J| Azarpazhooh|Amir|A| Kishen|Anil|A|

Caries-risk
acidogenic-profile
saliva
optical sensor


Long Noncoding RNA NONHSAT079852.2 Contributes to GBM Recurrence by Functioning as a ceRNA for has-mir-10401-3p to Facilitate HSPA1A Upregulation.

Abstract: Glioblastoma multiforme (GBM) is the most common brain malignancy and major cause of high mortality in patients with GBM, and its high recurrence rate is its most prominent feature. However, the pathobiological mechanisms involved in recurrent GBM remain largely unknown. Here, whole-transcriptome sequencing (RNA-sequencing, RNA-Seq) was used in characterizing the expression profile of recurrent GBM, and the aim was to identify crucial biomarkers that contribute to GBM relapse. Differentially expressed RNAs in three recurrent GBM tissues compared with three primary GBM tissues were identified through RNA-Seq. The function and mechanism of a candidate long noncoding RNA (lncRNA) in the progression and recurrence of GBM were elucidated by performing comprehensive bioinformatics analyses, such as functional enrichment analysis, protein-protein interaction prediction, and lncRNA-miRNA-mRNA regulatory network construction, and a series of in vitro assays. As the most significantly upregulated gene identified in recurrent GBM, HSPA1A is mainly related to antigen presentation and the MAPK signaling pathway, as indicated by functional enrichment analysis. HSPA1A was predicted as the target gene of the lncRNA NONHSAT079852.2. qRT-PCR revealed that NONHSAT079852.2 was significantly elevated in recurrent GBM relative to that in primary GBM, and high NONHSAT079852.2 expression was associated with the poor overall survival rates of patients with GBM. The knockdown of NONHSAT079852.2 successfully induced tumor cell apoptosis, inhibited the proliferation, migration, invasion and the expression level of HSPA1A in glioma cells. NONHSAT079852.2 was identified to be a sponge for hsa-miR-10401-3p through luciferase reporter assay. Moreover, HSPA1A was targeted and regulated by hsa-miR-10401-3p. Collectively, the results suggested that NONHSAT079852.2 acts as a sponge of hsa-mir-10401-3p and thereby enhances HSPA1A expression, promotes tumor cell proliferation and invasion, and leads to the progression and recurrence of GBM. This study will provide new insight into the regulatory mechanisms of NONHSAT079852.2-mediated competing endogenous RNA in the pathogenesis of recurrent GBM and evidence of the potential of lncRNAs as diagnostic biomarkers or potential therapeutic targets.

Zhao|Ningning|N| Zhang|Jiajie|J| Zhao|Lili|L| Fu|Xiaoni|X| Zhao|Qian|Q| Chao|Min|M| Cao|Haiyan|H| Jiao|Yang|Y| Hu|Yaqin|Y| Chen|Chao|C| Wang|Liang|L| Wang|Huijuan|H|

ceRNA
HSPA1A
RNA-sequencing
lncRNAs
recurrent glioblastoma multiforme


Incidence of unexpected positive histology in kyphoplasty.

Abstract:
OBJECTIVE
Kyphoplasty and vertebroplasty have become one of the most frequent surgical procedures in the treatment of vertebral compression fractures. Often, the cause of compression fractures is lowered bone mineral density as in osteoporosis. In the differential workup, also pathologic vertebral compression fractures need to be ruled out. Importantly, imaging techniques alone cannot safely differentiate between invasive lymphatic and osteoporotic vertebral fracture. Our goal was to identify the degree of unexpected positive histology in kyphoplasty for presumed osteoporotic vertebral compression fracture.

METHODS
We retrospectively analyzed all kyphoplasties performed between 2007 and 2015 at our institution. The data were acquired by reviewing our medical documentation system. The data analysis was done using Microsoft Excel. The statistical analysis was done using the Chi-squared test.

RESULTS
We performed 130 kyphoplasties/vertebroplasties. A biopsy was taken in 97 (74.6%) cases. In 10 (10.3%) cases, the histology revealed a pathological fracture. From these patients, only in 3 (30%) cases, a positive histology was not expected. Meaning that there was no history of cancer and the radiological findings presumed an osteoporotic fracture.

CONCLUSIONS
Therefore, we could demonstrate that the incidence of unexpected positive histology in vertebral compression fracture treated with kyphoplasty is significant (3.1%). As a conclusion, if a kyphoplasty is performed due to assumed osteoporotic vertebral compression fracture, a biopsy should be taken to safely rule out a pathological fracture caused by lymphatic bony invasion.

Kyphoplasty
Osteoporosis
Vertebral fracture
Lymphoma


Open acetabular fracture: Case report and literature review.

Abstract: Acetabular fractures are a rare injury, with a reported annual incidence of 3 patients per 100,000 per year. Open fractures of the acetabulum are extremely rare, with only explosive penetrating trauma (blast or gunshot injury) being previously reported. An open acetabular fracture as a result of blunt trauma is presented, in which the only indication was a wound in the buttock, in which early definitive surgical management of the injury provided a good clinical outcome.

Shiels|Sarah J|SJ|
Stevens|Jarrad M|JM|
Chesser|Timothy J S|TJS|


Cold-induced beigeing of stem cell-derived adipocytes is not fully reversible after return to normothermia.

Abstract: Beige adipocytes possess the morphological and biochemical characteristics of brown adipocytes, including the mitochondrial uncoupling protein (UCP)1. Mesenchymal stem cells (MSCs) are somatic multipotent progenitors which differentiate into lipid-laden adipocytes. Induction of MSC adipogenesis under hypothermic culture conditions (ie 32°C) promotes the appearance of a beige adipogenic phenotype, but the stability of this phenotypic switch after cells are returned to normothermic conditions of 37°C has not been fully examined. Here, cells transferred from 32°C to 37°C retained their multilocular beige-like morphology and exhibited an intermediate gene expression profile, with both beige-like and white adipocyte characteristics while maintaining UCP1 protein expression. Metabolic profile analysis indicated that the bioenergetic status of cells initially differentiated at 32°C adapted post-transfer to 37°C, showing an increase in mitochondrial respiration and glycolysis. The ability of the transferred cells to respond under stress conditions (eg carbonyl cyanide-4-phenylhydrazone (FCCP) treatment) demonstrated higher functional capacity of enzymes involved in the electron transport chain and capability to supply substrate to the mitochondria. Overall, MSC-derived adipocytes incubated at 32°C were able to remain metabolically active and retain brown-like features after 3 weeks of acclimatization at 37°C, indicating these phenotypic characteristics acquired in response to environmental conditions are not fully reversible.

stem cell
differentiation
adipogenesis
brown adipose tissue
temperature


New Glycosylated Dihydrochalcones Obtained by Biotransformation of 2'-Hydroxy-2-methylchalcone in Cultures of Entomopathogenic Filamentous Fungi.

Abstract: Flavonoids, including chalcones, are more stable and bioavailable in the form of glycosylated and methylated derivatives. The combined chemical and biotechnological methods can be applied to obtain such compounds. In the present study, 2'-hydroxy-2-methylchalcone was synthesized and biotransformed in the cultures of entomopathogenic filamentous fungi Beauveria bassiana KCH J1.5, Isaria fumosorosea KCH J2 and Isaria farinosa KCH J2.6, which have been known for their extensive enzymatic system and ability to perform glycosylation of flavonoids. As a result, five new glycosylated dihydrochalcones were obtained. Biotransformation of 2'-hydroxy-2-methylchalcone by B. bassiana KCH J1.5 resulted in four glycosylated dihydrochalcones: 2'-hydroxy-2-methyldihydrochalcone 3'-O-β-d-(4″-O-methyl)-glucopyranoside, 2',3-dihydroxy-2-methyldihydrochalcone 3'-O-β-d-(4″-O-methyl)-glucopyranoside, 2'-hydroxy-2-hydroxymethyldihydrochalcone 3'-O-β-d-(4″-O-methyl)-glucopyranoside, and 2',4-dihydroxy-2-methyldihydrochalcone 3'-O-β-d-(4″-O-methyl)-glucopyranoside. In the culture of I. fumosorosea KCH J2 only one product was formed-3-hydroxy-2-methyldihydrochalcone 2'-O-β-d-(4″-O-methyl)-glucopyranoside. Biotransformation performed by I. farinosa KCH J2.6 resulted in the formation of two products: 2'-hydroxy-2-methyldihydrochalcone 3'-O-β-d-(4″-O-methyl)-glucopyranoside and 2',3-dihydroxy-2-methyldihydrochalcone 3'-O-β-d-(4″-O-methyl)-glucopyranoside. The structures of all obtained products were established based on the NMR spectroscopy. All products mentioned above may be used in further studies as potentially bioactive compounds with improved stability and bioavailability. These compounds can be considered as flavor enhancers and potential sweeteners.

glycosylation
biotransformations
flavonoids
Beauveria bassiana
Isaria fumosorosea
Isaria farinosa
O-methylglucosides
methylchalcone


CRISPR -Mediated Expression of the Fetal Scn5a Isoform in Adult Mice Causes Conduction Defects and Arrhythmias.

Abstract: Background The sodium channel, Nav1.5, encoded by SCN 5A, undergoes developmentally regulated splicing from inclusion of exon 6A in the fetal heart to exon 6B in adults. These mutually exclusive exons differ in 7 amino acids altering the electrophysiological properties of the Nav1.5 channel. In myotonic dystrophy type 1, SCN 5A is mis-spliced such that the fetal pattern of exon 6A inclusion is detected in adult hearts. Cardiac manifestations of myotonic dystrophy type 1 include conduction defects and arrhythmias and are the second-leading cause of death. Methods and Results This work aimed to determine the impact of SCN 5A mis-splicing on cardiac function. We used clustered regularly interspaced short palindromic repeat ( CRISPR) /CRISPR-associated protein 9 (Cas9) to delete Scn5a exon 6B in mice, thereby redirecting splicing toward exon 6A. These mice exhibit prolonged PR and QRS intervals, slowed conduction velocity, extended action potential duration, and are highly susceptible to arrhythmias. Conclusions Our findings highlight a nonmutational pathological mechanism of arrhythmias and conduction defects as a result of mis-splicing of the predominant cardiac sodium channel. Animals homozygous for the deleted exon express only the fetal isoform and have more-severe phenotypes than heterozygotes that also express the adult isoform. This observation is directly relevant to myotonic dystrophy type 1, and possibly pathological arrhythmias, in which individuals differ with regard to the ratios of the isoforms expressed.

Pang|Paul D|PD|
Alsina|Katherina M|KM|
Cao|Shuyi|S|
Koushik|Amrita B|AB|
Wehrens|Xander H T|XHT|
Cooper|Thomas A|TA|

D064112:Clustered Regularly Interspaced Short Palindromic Repeats

D018507:Gene Expression Regulation, Developmental

D062554:NAV1.5 Voltage-Gated Sodium Channel

SCN5A
conduction
arrhythmia
alternative splicing
myotonic dystrophy cardiomyopathy


Foster children's attachment representations: the role of type of maltreatment and the relationship with birth family.

Abstract: Children in foster care are at risk of developing insecure and disorganized attachment, which is problematic for establishing new relationships in foster families. However, most previous studies have focused on attachment behaviors in young children rather than on attachment representations. We compared foster children's attachment representations with those of a community group, analyzing also the contribution made by different factors to foster children's attachment representations. We assessed the attachment representations of 109 children aged between 4 and 9 years (51 children in non-kin foster care and 58 community children) in southern Spain, using a narrative story stem measure. Case records information were collected for adversity and child protection variables. Foster children had fewer security and more avoidance indicators than their community counterparts, with those who had suffered more severe maltreatment scoring lower for security and higher for disorganization. Exposure to physical and emotional abuse and birth parents' opposition to the foster placement predicted more disorganized attachment representations. Interventions with foster children should consider their heterogeneity in terms of attachment outcomes, and foster caregivers of abused children may need guidance in order to provide therapeutic caregiving.

Attachment representations
maltreatment
birth family
foster care
early adversity


Arginine-rich peptide/platinum hybrid colloid nanoparticle cluster: A single nanozyme mimicking multi-enzymatic cascade systems in peroxisome.

Abstract: Recently, nanozymes have attracted sustained attention for facilitating next generation of artificial enzymatic cascade systems (ECSs). However, the fabrication of integrated multi-ECSs based on a single nanozyme remains a great challenge. Here, inspired by the biological function and self-assembling ability of arginine (R), we synthesized arginine-rich peptide-Pt nanoparticle cluster (ARP-PtNC) nanozymes that mimic two typical enzymatic cascade systems of uricase/catalase and superoxide dismutase/catalase in natural peroxisome. ARPs containing at least 10 arginine residues contribute to the cluster formation based on hydrogen bonding and coordination. The well-designed peptide-Pt hybrid nanozyme not only possesses excellent uricase-mimicking activity to degrade uric acid effectively, but also serves as a desired scavenger for reactive oxygen species (ROS) harnessing two efficient enzyme cascade catalysis of uricase/catalase and superoxide dismutase/catalase. The surface microenvironment of the hybrid nanozymes provided by arginine-rich peptides and the cluster structure contribute to the efficient multiply enzyme-like activities. Fascinatingly, the hybrid nanozyme can inhibit the formation of monosodium urate monohydrate effectively based on the architecture of ARP-PtNCs. Thus, ARP-PtNC nanozyme has the potential in gout and hyperuricemia therapy. Rational design of ingenious peptide-metal hybrid nanozyme with unique physicochemical surface properties provides a versatile and designed strategy to fabricate multi-enzymatic cascade systems, which opens new avenues to broaden the application of nanozymes in practice.

Liu|Yan|Y| Qin|Yuling|Y| Zhang|Qianya|Q| Zou|Wenting|W| Jin|Lingcen|L| Guo|Rong|R|

Arginine-rich peptide
Nanoparticle cluster
Cascade
Uricase
Microenvironment
Multi-enzyme activities


Local FK506 dose-dependent study using a novel three-dimensional organotypic assay.

Abstract: Local administration of FK506, an FDA approved immunosuppressant with neuroregenerative properties, is a promising technique to achieve improved peripheral nerve regeneration while preventing the side effects associated with the systemic administration of this drug. Although considerable research has been devoted to the development of clinically suitable systems for local delivery of FK506 to the site of nerve injury and repair, the optimal dose of FK506 for enhancement of axon regeneration in the peripheral nerve has not yet been established. To this end, we devised a three-dimensional (3D) organotypic assay capable of mimicking the peripheral nerve. This assay consisted of a neonatal rat dorsal root ganglion (DRG) extending its neurites into the native peripheral nerve scaffold provided by an acellular nerve allograft (ANA). A novel 3D compartmented cell culture system was adapted from the 3D organotypic assay to achieve local delivery of FK506 just to the growing neurites in vitro and establish the required local dose of FK506 for peripheral nerve regeneration. A bimodal dose response was observed by culturing the entire DRG-ANA construct with media containing different concentrations of FK506. Low drug concentration of 1 pg/ml and high drug concentration of 100 ng/ml lead to the longest neurite extension in vitro. Furthermore, regardless of the FK506 concentration, concentrating the drug to the growing neurites resulted in significant increase in both neurite extension and neurite density, an effect that was not observed with the FK506 delivery to both neurites and neural cell bodies within DRG. The findings in this study provide valuable insight into the optimal local dose of FK506 for peripheral nerve regeneration. Furthermore, for the first time, this study suggests the potential interaction of FK506 with axons at the level of the growth cone.

Tajdaran|Kasra|K|0000-0001-7370-9705
Chan|Katelyn|K|
Zhang|Jennifer|J|
Gordon|Tessa|T|
Borschel|Gregory H|GH|

FK506
dose-dependent study
organotypic assay
peripheral nerve regeneration
biomaterial
local drug delivery
rat model
regenerative medicine


Responsibility Without Freedom? Folk Judgements About Deliberate Actions.

Abstract: A long-standing position in philosophy, law, and theology is that a person can be held morally responsible for an action only if they had the freedom to choose and to act otherwise. Thus, many philosophers consider freedom to be a necessary condition for moral responsibility. However, empirical findings suggest that this assumption might not be in line with common sense thinking. For example, in a recent study we used surveys to show that - counter to positions held by many philosophers - lay people consider actions to be free when they are spontaneous rather than being based on reasons. In contrast, responsibility is often considered to require that someone has thought about the alternative options. In this study we used an online survey to directly test the degree to which lay judgements of freedom and responsibility match. Specifically, we tested whether manipulations of deliberation affect freedom and responsibility judgements in the same way. Furthermore, we also tested the dependency of these judgements on a person's belief that their decision had consequences for their personal life. We found that deliberation had an opposite effect on freedom and responsibility judgements. People were considered more free when they acted spontaneously, whereas they were considered more responsible when they deliberated about their actions. These results seem to suggest that deliberating about reasons is crucially important for the lay concept of responsibility, while for the lay notion of freedom it is perceived to be detrimental. One way of interpreting our findings for the interdisciplinary debate on free will and responsibility could be to suggest that lay beliefs match the philosophical position of semi-compatibilism. Semi-compatibilists insist that the metaphysical debate on the nature of free will can be separated from the debate on conditions of responsible agency. According to our findings the beliefs of lay people are in line with views held by semi-compatibilists, even though we did not test whether they endorse that position explicitly.

Vierkant|Tillmann|T| Deutschländer|Robert|R| Sinnott-Armstrong|Walter|W| Haynes|John-Dylan|JD|

responsibility
freedom
deliberation
consequence
experimental philosophy


Health related quality of life in adolescent cochlear implant users.

Abstract: Objective: Children with significant hearing loss (HL) are at risk for lower self-esteem and lower perceived quality of life (QoL). This study examined how self-reported QoL of adolescents cochlear implant (CI) users compared to that of adolescents with normal hearing, and examined if factors such as socioeconomic status (SES) and communication methodology affect QoL and speech recognition. Methods: Forty-three adolescent CI users completed a 34-item questionnaire that included questions adapted from the QoL of Deaf or Hard-of-Hearing Youth questionnaire (Seattle Quality of Life Group SEAQOL. 2010 Quality of life of deaf or hard-of-hearing youth (YQOL-DHH). Seattle, Washington) and from the Kidscreen-10 Index (The KIDSCREEN Group, Europe, 2006, the KIDSCREEN questionnaires - quality of life questionnaires for children and adolescents handbook. Lengerich: Pabst Science Publishers. All subjects received their first CI prior to the age of 5, and ranged in age from 10-17 years at the time of survey completion. Results: Adolescents with CIs demonstrated self-reported QoL scores similar to children with normal hearing. Lower SES and communication mode appear to influence speech recognition, and also appear to impact self-reported QoL in different ways. Conclusions: Examination of communication outcomes, along with other factors that influence QoL, such as SES, will help clinicians identify children at risk for low QoL. Such identification will help generate appropriate referrals to enhance QoL in adolescent CI users.

Hofmann|Margarita|M|
Meloche|Melanie|M|
Zwolan|Teresa A|TA|0000-0002-5740-268X

Quality of Life
Adolescents
Hearing Loss
Self-esteem
Cochlear Implant(s)


Probing the inherent stability of siRNA immobilized on nanoparticle constructs.

Abstract: Small interfering RNA (siRNA) is a powerful and highly effective method to regulate gene expression in vitro and in vivo. However, the susceptibility to serum nuclease-catalyzed degradation is a major challenge and it remains unclear whether the strategies developed to improve the stability of siRNA free in serum solution are ideal for siRNA conjugated to nanoparticle surfaces. Herein, we use spherical nucleic acid nanoparticle conjugates, consisting of gold nanoparticles (AuNPs) with siRNA chemisorbed to the surface, as a platform to study how a model siRNA targeting androgen receptor degrades in serum (SNA-siRNAAR). In solutions of 10% (vol/vol) FBS, we find rapid endonuclease hydrolysis at specific sites near the AuNP-facing terminus of siRNAAR, which were different from those of siRNAAR free in solution. These data indicate that the chemical environment of siRNA on a nanoparticle surface can alter the recognition of siRNA by serum nucleases and change the inherent stability of the nucleic acid. Finally, we demonstrate that incorporation of 2'-O-methyl RNA nucleotides at sites of nuclease hydrolysis on SNA-siRNAAR results in a 10-fold increase in siRNA lifetime. These data suggest that strategies for enhancing the serum stability of siRNA immobilized to nanoparticles must be developed from a dedicated analysis of the siRNA-nanoparticle conjugate, rather than a reliance on strategies developed for siRNA free in solution. We believe these findings are important for fundamentally understanding interactions between biological media and oligonucleotides conjugated to nanoparticles for the development of gene regulatory and therapeutic agents in a variety of disease models.

Barnaby|Stacey N|SN|
Lee|Andrew|A|
Mirkin|Chad A|CA|

OliGreen
biological recognition
nanotechnology
polyacrylamide gel electrophoresis


Delayed Spinal Arachnoiditis Following Aneurysmal Subarachnoid Hemorrhage: A Case Report.

Abstract: Spinal arachnoiditis (SA) is a rare and delayed complication of aneurysmal subarachnoid hemorrhage (aSAH). We present a case of delayed SA associated with thoracic and lumbar arachnoid cysts in a patient with aSAH secondary to a ruptured vertebral artery aneurysm. The patient underwent a thoracic laminectomy for decompression of the spinal cord, lysis of arachnoid adhesions, and fenestration of an arachnoid cyst. We present the pathogenesis, diagnosis, treatment, and management of spinal arachnoiditis as a rare complication of aSAH.

Dossani|Rimal H|RH|
Patra|Devi P|DP|
Sun|Hai|H|
Nanda|Anil|A|
Cuellar|Hugo|H|

spinal arachnoiditis
subarachnoid hemorrhage
spinal arachnoid cyst


Abstract:
INTRODUCTION
Psoriasis is a chronic, multisystem, inflammatory, disfiguring disease with a high negative impact on quality of life due to comorbid psychological, organic, and sexual consequences.

AIM
To evaluate the psychopathological and sexual aspects of psoriasis vulgaris in patients and their partners compared to healthy controls.

METHODS
In the current comparative cross-sectional study, the sample included 220 psoriasis vulgaris patients (110 males and 110 females), their consenting partners, and 220 age- and sex-matched healthy controls. All participants were evaluated for depression and anxiety using the Hospital Anxiety and Depression Scale and for low self-esteem using the Rosenberg's Self-Esteem Questionnaire. Sexual function was assessed in females using the Female Sexual Function Index questionnaire and in males using the International Index of Erectile Function and its abbreviated 5-item version. For male patients suffering from erectile dysfunction, hormonal assessment and penile duplex ultrasound were added.

MAIN OUTCOME MEASURE
The main outcome measures were frequency of depression, anxiety, low self-esteem, and sexual dysfunction in psoriasis vulgaris patients, partners, and controls; the domains of sexual function affected in the studied groups; and the etiology of erectile dysfunction in affected psoriatic males.

RESULTS
Frequency of depression, anxiety, and low self-esteem were significantly higher in psoriasis patients of both sexes compared with controls. Sexual dysfunction followed the same trend of being significantly higher in cases when compared to controls. Females had a significantly higher frequency of sexual dysfunction than males. Sexual dysfunction in both sexes involved multiple domains of the sexual response cycle, with depression and genital affection by psoriasis being risk factors in both sexes and disease severity being an additional risk factor in females. Erectile dysfunction was mainly psychogenic in origin in male patients.

CLINICAL IMPLICATIONS
Assessment of psychopathological and sexual comorbidities in psoriasis patients and partners should be an integral part of the management plan and should be added to the guidelines of the disease.

STRENGTH & LIMITATIONS
This study is of sufficient power to draw solid conclusions. Assessment of the partners and determination of the sexual domains affected by the disease and nature of erectile dysfunction in males are points of novelty. The cross-sectional design is a limitation of the study.

CONCLUSION
Psoriatic patients of both sexes and their partners suffer from a high burden of psychopathological and sexual consequences that are related to disease distribution and severity. Alariny AF, Farid CI, Elweshahi HM, et al. Psychological and Sexual Consequences of Psoriasis Vulgaris on Patients and Their Partners. J Sex Med 2019; 16:1900-1911.

Alariny|Ali Fouad|AF|
Farid|Carmen Ibrahim|CI|
Elweshahi|Heba Mahmoud|HM|
Abbood|Sahar Salim|SS|

Psoriasis Vulgaris
Partners
Depression
Anxiety
Low Self-Esteem
Erectile Dysfunction
Sexual Dysfunction


LGI1 antibody encephalitis and psychosis.

Abstract:
OBJECTIVE:
To describe a case of leucine-rich, glioma inactivated 1 antibody-encephalitis presenting with psychosis.

METHODS:
Case report.

RESULTS:
A young man with leucine-rich, glioma inactivated 1-antibody encephalitis initially presented with acute psychotic symptoms, short-term memory loss and faciobrachial dystonic seizures. Magnetic resonance imaging revealed hippocampal lesions. Electroencephalography revealed frontotemporal slowing of background activity.

CONCLUSION:
Increased awareness of leucine-rich, glioma inactivated 1-antibody encephalitis may promote early recognition and treatment.

Wang|Dahai|D| Hao|Qinjian|Q| He|Lan|L| Wang|Qiang|Q|

D047908:Intracellular Signaling Peptides and Proteins

LGI1 antibody encephalitis
psychosis
misdiagnosis


Monitoring TIGIT/DNAM-1 and PVR/PVRL2 Immune Checkpoint Expression Levels in Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia.

Abstract: After allogeneic stem cell transplantation (alloSCT), several immune checkpoints play an important role in the antileukemic immune response in the bone marrow (BM) microenvironment. However, immune checkpoint expression levels in the BM have not been reported after alloSCT in patients with acute myeloid leukemia (AML). We investigated the clinical impact of immune checkpoint expression in BM samples after alloSCT for AML. Higher expression of T cell immunoreceptor with Ig and ITIM domains (TIGIT) was associated with a decreased incidence of acute graft-versus-host disease (P = .048) and poor overall (P = .046) and progression-free survival (P = 0.024). In addition, higher expression of TIGIT at engraftment after alloSCT was correlated with a decreased number of natural killer cells in BM (P = .019). Monitoring TIGIT expression in the BM could be useful for predicting outcome after alloSCT for AML. Our findings raise the possibility that blockade of TIGIT would improve survival.

Hattori|Norimichi|N| Kawaguchi|Yukiko|Y| Sasaki|Yohei|Y| Shimada|Shotaro|S| Murai|So|S| Abe|Maasa|M| Baba|Yuta|Y| Watanuki|Megumi|M| Fujiwara|Shun|S| Arai|Nana|N| Kabasawa|Nobuyuki|N| Tsukamoto|Hiroyuki|H| Uto|Yui|Y| Yanagisawa|Kouji|K| Saito|Bungo|B| Harada|Hiroshi|H| Nakamaki|Tsuyoshi|T|

D018380:Hematopoietic Stem Cell Transplantation

TIGIT
DNAM-1
PVR
Immune checkpoints
Allogeneic stem cell transplantation
PVRL1


The Cytokine IL-1β and Piperine Complex Surveyed by Experimental and Computational Molecular Biophysics.

Abstract: The bioactive piperine, a compound found in some pepper species, has been widely studied because of its therapeutic properties that include the inhibition of an important inflammation pathway triggered by interleukin-1 beta (IL-1β). However, investigation into the molecular interactions between IL-1β and piperine is not reported in the literature. Here, we present for the first time the characterisation of the complex formed by IL-1β and piperine through experimental and computational molecular biophysical analyses. Fluorescence spectroscopy unveiled the presence of one binding site for piperine with an affinity constant of 14.3 × 104 M-1 at 298 K. The thermodynamic analysis indicated that the interaction with IL-1β was spontaneous (∆G = -25 kJ/mol) and, when split into enthalpic and entropic contributions, the latter was more significant. Circular dichroism spectroscopy showed that piperine did not affect IL-1β secondary structure (~2%) and therefore its stability. The set of experimental data parameterized the computational biophysical approach. Through molecular docking, the binding site micro-environment was revealed to be composed mostly by non-polar amino acids. Furthermore, molecular dynamics, along with umbrella sampling, are in agreement with the thermodynamic parameters obtained by fluorescence assays and showed that large protein movements are not present in IL-1β, corroborating the circular dichroism data.

cytokine
IL-1β
piperine
fluorescence spectroscopy
molecular docking
umbrella sampling


Preparation, stability, and photoreactivity of thiolato ruthenium polypyridyl complexes: Can cysteine derivatives protect ruthenium-based anticancer complexes?

Abstract: Ruthenium polypyridyl complexes may act as light-activatable anticancer prodrugs provided that they are protected by well-coordinated ligands that i) prevent coordination of other biomolecules to the metal center in the dark and ii) can be removed by visible light irradiation. In this paper, the use of monodentate thiol ligands RSH as light-cleavable protecting groups for the ruthenium complex [Ru(tpy)(bpy)(OH2)](PF6)2 ([1](PF6)2; tpy=2,2';6',2″-terpyridine, bpy=2,2'-bypyridine), is investigated. The reaction of [1](2+) with RSH=H2Cys (L-cysteine), H2Acys (N-acetyl-L-cysteine), and HAcysMe (N-acetyl-L-cysteine methyl ester), is studied by UV-visible spectroscopy, NMR spectroscopy, and mass spectrometry. Coordination of the monodentate thiol ligands to the ruthenium complex takes place upon heating to 353 K, but full conversion to the protected complex [Ru(tpy)(bpy)(SR)]PF6 is only possible when a large excess of ligand is used. Isolation and characterization of the two new thiolato complexes [Ru(tpy)(bpy)(κS-HCys)]PF6 ([2]PF6) and [Ru(tpy)(bpy)(κS-HAcys)]PF6 ([3]PF6) is reported. [3]PF6 shows a metal-to-ligand charge-transfer absorption band that is red shifted (λmax=492 nm in water) compared to its methionine analogue [Ru(tpy)(bpy)(κS-HAmet)](Cl)2 ([5](Cl)2, λmax=452 nm; HAmet=N-acetyl-methionine). In the dark the thiolate ligand coordinated to ruthenium is oxidized even by traces of oxygen, which first leads to the sulfenato, sulfinato, and disulfide ruthenium complexes, and finally to the formation of the aqua complex [1](2+). [3]PF6 showed slow photosubstitution of the thiolate ligand by water under blue light irradiation, together with faster photooxidation of the thiolate ligand compared to dark conditions. The use of thiol vs. thioether monodentate ligands is discussed for the protection of anticancer ruthenium-based prodrugs.

van Rixel|Vincent H S|VH|
Busemann|Anja|A|
Göttle|Adrien J|AJ|
Bonnet|Sylvestre|S|

D066244:Proton Magnetic Resonance Spectroscopy

Protecting group
Metallodrug
Photoactivated chemotherapy
Photopharmacology
Sulfur


Genomic and phylogenetic characterization of Shewanella xiamenensis isolated from giant grouper (Epinephelus lanceolatus) in Taiwan.

Abstract: Shewanella xiamenensis is an emerging pathogen causing intra-abdominal infection and intestinal colonization. Epidemiologic clues suggest its role as a potential food-borne zoonotic agent. To date, four genome sequences of S. xiamenensis have been made publicly available. All of them were isolated from water samples. In this study, we characterized the genome of a S. xiamenensis strain isolated from a giant grouper in Taiwan. The genome of S. xiamenensis ZYW1 is 4,827,717 bp in length and encodes 4,239 open reading frames. Its genomic sequence shares high homology with other S. xiamenensis strains. blaOXA-416 was identified. This is the first detection of S. xiamenensis in Taiwan. These genomic data and analyses contribute to our understanding of S. xiamenensis and may help to elucidate disease-causing mechanisms in future studies.

Huang|Yao-Ting|YT| Cheng|Jan-Fang|JF| Wu|Zong-Yen|ZY| Tung|Kwong-Chung|KC| Chen|Ying-Ju|YJ| Hong|Yu-Kai|YK| Chen|Shi-Yu|SY| Liu|Po-Yu|PY|0000-0001-8006-4917

Shewanella xiamenensis
giant grouper
aquaculture
phylogeny
whole-genome sequencing


Head-to-head comparison of contemporary heart failure risk scores.

Abstract:
AIMS
Several heart failure (HF) web-based risk scores are currently used in clinical practice. Currently, we lack head-to-head comparison of the accuracy of risk scores. This study aimed to assess correlation and mortality prediction performance of Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC-HF) risk score, which includes clinical variables + medications; Seattle Heart Failure Model (SHFM), which includes clinical variables + treatments + analytes; PARADIGM Risk of Events and Death in the Contemporary Treatment of Heart Failure (PREDICT-HF) and Barcelona Bio-Heart Failure (BCN-Bio-HF) risk calculator, which also include biomarkers, like N-terminal pro B-type natriuretic peptide (NT-proBNP).

METHODS AND RESULTS
A total of 1166 consecutive patients with HF from different aetiologies that had NT-proBNP measurement at first visit were included. Discrimination for all-cause mortality was compared by Harrell's C-statistic from 1 to 5 years, when possible. Calibration was assessed by calibration plots and Hosmer-Lemeshow test and global performance by Nagelkerke's R2 . Correlation between scores was assessed by Spearman rank test. Correlation between the scores was relatively poor (rho value from 0.66 to 0.79). Discrimination analyses showed better results for 1-year mortality than for longer follow-up (SHFM 0.817, MAGGIC-HF 0.801, PREDICT-HF 0.799, BCN-Bio-HF 0.830). MAGGIC-HF showed the best calibration, BCN-Bio-HF overestimated risk while SHFM and PREDICT-HF underestimated it. BCN-Bio-HF provided the best discrimination and overall performance at every time-point.

CONCLUSIONS
None of the contemporary risk scores examined showed a clear superiority over the rest. BCN-Bio-HF calculator provided the best discrimination and overall performance with overestimation of risk. MAGGIC-HF showed the best calibration, and SHFM and PREDICT-HF tended to underestimate risk. Regular updating and recalibration of online web calculators seems necessary to improve their accuracy as HF management evolves at unprecedented pace.

Codina|Pau|P|
Lupón|Josep|J|
Borrellas|Andrea|A|
Spitaleri|Giosafat|G|
Cediel|Germán|G|
Domingo|Mar|M|
Simpson|Joanne|J|
Levy|Wayne C|WC|
Santiago-Vacas|Evelyn|E|
Zamora|Elisabet|E|
Buchaca|David|D|
Subirana|Isaac|I|
Santesmases|Javier|J|
Diez-Quevedo|Crisanto|C|
Troya|Maria I|MI|
Boldo|Maria|M|
Altmir|Salvador|S|
Alonso|Nuria|N|
González|Beatriz|B|
Rivas|Carmen|C|
Nuñez|Julio|J|
McMurray|John|J|
Bayes-Genis|Antoni|A|

Heart failure
Mortality
Risk models
Risk prediction


Mitochondrial dismissal in mammals, from protein degradation to mitophagy.

Abstract: Mitochondria are double-membraned highly dynamic organelles; the shape, location and function of which are determined by a constant balance between opposing fusion and fission events. A fine modulation of mitochondrial structure is crucial for their correct functionality and for many physiological cell processes, the status of these organelles, being thus a key aspect in a cell's fate. Indeed, the homeostasis of mitochondria needs to be highly regulated for the above mentioned reasons, and since a) they are the major source of energy; b) they participate in various signaling pathways; albeit at the same time c) they are also the major source of reactive oxygen species (ROS, the main damaging detrimental players for all cell components). Elaborate mechanisms of mitochondrial quality control have evolved for maintaining a functional mitochondrial network and avoiding cell damage. The first mechanism is the removal of damaged mitochondrial proteins within the organelle via chaperones and protease; the second is the cytosolic ubiquitin-proteasome system (UPS), able to eliminate proteins embedded in the outer mitochondrial membrane; the third is the removal of the entire mitochondria through mitophagy, in the case of extensive organelle damage and dysfunction. In this review, we provide an overview of these mitochondria stability and quality control mechanisms, highlighting mitophagy, and emphasizing the central role of mitochondrial dynamics in this context. This article is part of a Special Issue entitled: Dynamic and ultrastructure of bioenergetic membranes and their components.

Autophagy
Mitochondria Quality Control
Mitochondria fusion/fission
Mitochondrion
Neurodegeneration
Ubiquitylation


Is There a Relationship Between Kinesiophobia and Physical Activity Level in Patients with Knee Osteoarthritis?

Abstract:
OBJECTIVE
To investigate the levels of kinesiophobia, physical activity, depression, disability, and quality of life in patients with knee osteoarthritis.

DESIGN
A cross-sectional study.

SETTING
A tertiary health care center.

SUBJECTS
Ninety-six patients with knee osteoarthritis.

METHODS
Pain intensity was evaluated by the Visual Analog Scale, kinesiophobia by the Tampa Scale of Kinesiophobia and Brief Fear of Movement Scale, depression by the Beck Depression Inventory, disability by the Western Ontario and McMaster Universities Arthritis Index, physical activity level by the International Physical Activity Questionnaire short form, and quality of life by the Short Form 12 Health Survey Questionnaire.

RESULTS
Of the patients, 85.7% had high-level kinesiophobia, 70.6% had depression, and 64.4% had low, 27.8% moderate, and 7.8% high physical activity levels. Age, activity-related pain score of the Visual Analog Scale, Tampa Scale of Kinesiophobia and Brief Fear of Movement Scale scores, and Western Ontario and McMaster Universities Arthritis Index and Beck Depression Inventory scores were higher in the group with high-level kinesiophobia, whereas the mental, physical, and total scores obtained from the Short Form 12 Health Survey Questionnaire were higher in the group with low-level kinesiophobia (P < 0.05).

CONCLUSIONS
As the treatment of pain alone in patients with knee osteoarthritis is not sufficient to reduce fear of movement, we suggest that approaches to increase awareness of fear of movement and physical activity and cognitive behavioral therapy related to fear of movement should be included in the treatment program.

Kinesiophobia
Knee Osteoarthritis
Disability
Tampa
Fear of Movement


Comparison of Microbial Populations in Saliva and Feces from Healthy and Celiac Adolescents with Conventional and Molecular Approaches after Cultivation on Gluten-Containing Media: An Exploratory Study.

Abstract: Microbes capable of metabolizing gluten are common in various parts of the intestinal tract. In this study, saliva and fecal samples were obtained from 10 adolescents (13-18 years of age), five of which had celiac disease (CD) and five of which were healthy volunteers (HV). Culture-enriched saliva and fecal samples were compared with molecular profiling, and microorganisms displaying lysis zones on gluten-containing media (i.e., gluten-degrading microorganisms; GDMs) were isolated. In total, 45 gluten-degrading strains were isolated, belonging to 13 genera and 15 species, including Candida albicans and Veillonella. GDMs were more common in HVs compared to CD patients and more diverse in saliva compared to feces. In saliva, GDMs showed partial overlap between HVs and CD patients. Bacterial communities in fecal samples determined with amplicon sequencing significantly differed between CD patients and HVs. Overall, 7-46 of all operational taxonomic units (OTUs) per sample were below the detection limit in the fecal samples but were present in the cultivated samples, and mainly included representatives from Lactobacillus and Enterococcus. Furthermore, differences in fecal short-chain fatty-acid concentrations between CD patients and HVs, as well as their correlations with bacterial taxa, were demonstrated.

Senicar|Tilen|T| Kukovicic|Andraz|A| Tkalec|Valerija|V| Mahnic|Aleksander|A| Dolinsek|Jernej|J| Rupnik|Maja|M|0000-0003-1930-3290

celiac disease
gluten-degrading microorganisms
Candida
Veillonella
sequencing
microbiota
short-chain fatty acids


Pattern of cerebral hyperperfusion in Alzheimer's disease and amnestic mild cognitive impairment using voxel-based analysis of 3D arterial spin-labeling imaging: initial experience.

Abstract:
PURPOSE
A three-dimensional (3D) continuous pulse arterial spin labeling (ASL) technique was used to investigate cerebral blood flow (CBF) changes in patients with Alzheimer's disease (AD), amnestic mild cognitive impairment (aMCI), and age- and sex-matched healthy controls.

MATERIALS AND METHODS
Three groups were recruited for comparison, 24 AD patients, 17 MCI patients, and 21 age- and sex-matched control subjects. Three-dimensional ASL scans covering the entire brain were acquired with a 3.0 T magnetic resonance scanner. Spatial processing was performed with statistical parametric mapping 8. A second-level one-way analysis of variance analysis (threshold at P<0.05) was performed on the preprocessed ASL data. An average whole-brain CBF for each subject was also included as group-level covariates for the perfusion data, to control for individual CBF variations.

RESULTS
Significantly increased CBF was detected in bilateral frontal lobes and right temporal subgyral regions in aMCI compared with controls. When comparing AD with aMCI, the major hyperperfusion regions were the right limbic lobe and basal ganglia regions, including the putamen, caudate, lentiform nucleus, and thalamus, and hypoperfusion was found in the left medial frontal lobe, parietal cortex, the right middle temporo-occipital lobe, and particularly, the left anterior cingulate gyrus. We also found decreased CBF in the bilateral temporo-parieto-occipital cortices and left limbic lobe in AD patients, relative to the control group. aMCI subjects showed decreased blood flow in the left occipital lobe, bilateral inferior temporal cortex, and right middle temporal cortex.

CONCLUSION
Our results indicated that ASL provided useful perfusion information in AD disease and may be used as an appealing alternative for further pathologic and neuropsychological studies, especially of compensatory mechanisms for cerebral hypoperfusion.

Ding|Bei|B|
Ling|Hua-wei|HW|
Zhang|Yong|Y|
Huang|Juan|J|
Zhang|Huan|H|
Wang|Tao|T|
Yan|Fu Hua|FH|

amnestic mild cognitive impairment
arterial spin labeling
Alzheimer’s disease
perfusion image


Engineering Copper Iodide (CuI) for Multifunctional p-Type Transparent Semiconductors and Conductors.

Abstract: Developing transparent p-type semiconductors and conductors has attracted significant interest in both academia and industry because metal oxides only show efficient n-type characteristics at room temperature. Among the different candidates, copper iodide (CuI) is one of the most promising p-type materials because of its widely adjustable conductivity from transparent electrodes to semiconducting layers in transistors. CuI can form thin films with high transparency in the visible light region using various low-temperature deposition techniques. This progress report aims to provide a basic understanding of CuI-based materials and recent progress in the development of various devices. The first section provides a brief introduction to CuI with respect to electronic structure, defect states, charge transport physics, and overviews the CuI film deposition methods. The material design concepts through doping/alloying approaches to adjust the optoelectrical properties are also discussed in the first section. The following section presents recent advances in state-of-the-art CuI-based devices, including transparent electrodes, thermoelectric devices, p-n diodes, p-channel transistors, light emitting diodes, and solar cells. In conclusion, current challenges and perspective opportunities are highlighted.

copper iodide
inorganic p‐type semiconductors
thin‐film transistors
transparent conductors


Selective intestinal decontamination for the prevention of early bacterial infections after liver transplantation.

Abstract: Bacterial infection in the first month after liver transplantation is a frequent complication that poses a serious risk for liver transplant recipients as contributes substantially to increased length of hospitalization and hospital costs being a leading cause of death in this period. Most of these infections are caused by gram-negative bacilli, although gram-positive infections, especially Enterococcus sp. constitute an emerging infectious problem. This high rate of early postoperative infections after liver transplant has generated interest in exploring various prophylactic approaches to surmount this problem. One of these approaches is selective intestinal decontamination (SID). SID is a prophylactic strategy that consists of the administration of antimicrobials with limited anaerobicidal activity in order to reduce the burden of aerobic gram-negative bacteria and/or yeast in the intestinal tract and so prevent infections caused by these organisms. The majority of studies carried out to date have found SID to be effective in the reduction of gram-negative infection, but the effect on overall infection is limited due to a higher number of infection episodes by pathogenic enterococci and coagulase-negative staphylococci. However, difficulties in general extrapolation of the favorable results obtained in specific studies together with the potential risk of selection of multirresistant microorganisms has conditioned controversy about the routinely application of these strategies in liver transplant recipients.

Resino|Elena|E|
San-Juan|Rafael|R|
Aguado|Jose Maria|JM|

Selective intestinal decontamination
Infection
Liver transplant
Multirresistant
Gram-negative bacterial infection
Gram-positive bacterial infection


Are Chinese Patients with Type 2 Diabetes and a Body Mass Index of 27.5-32.5 kg/m2 Suitable for Metabolic Surgery? A One-Year Post-Surgery Study.

Abstract:
INTRODUCTION
The aim of this study was to clarify the efficacy and safety of metabolic surgery in Chinese patients with type 2 diabetes mellitus (T2DM) and a body mass index (BMI) of 27.5-32.5 kg/m2.

METHODS
A total of 99 patients with T2DM were enrolled in this retrospective cohort study. Of these patients, 53 had a BMI of 27.5-32.5 kg/m2 and had undergone metabolic surgery (n = 21) or were on conventional antidiabetic therapy (n = 32)]; 46 had a BMI ≥ 32.5 kg/m2 and all had undergone metabolic surgery. Primary endpoints included the triple endpoint [hemoglobin A1c < 6.5%, low-density lipoprotein cholesterol (LDL-C) < 2.6 mmol/L, and systolic blood pressure (SBP) < 130 mmHg] and successful weight loss 1 year later. Remission of diabetes, glucose and lipid metabolism, medication usage, and adverse events were evaluated.

RESULTS
Of patients with BMI 27.5-32.5 kg/m2 undergoing metabolic surgery, 33.33% achieved the composite endpoints, and 100% achieved successful weight loss. This result was similar to that in patients with BMI ≥ 32.5 and better than those with BMI 27.5-32.5 kg/m2 receiving conventional antidiabetic therapy. A significant and similar reduction in BMI, waist circumference, SBP, serum LDL-C, hemoglobin A1c, and uric acid, as well as similar frequency postoperative adverse events, were confirmed in both metabolic surgery groups. Patients with BMI 27.5-32.5 kg/m2 who had undergonemetabolic surgery showed more metabolic improvement than those only receiving medications but they experienced more adverse events.

CONCLUSION
A BMI cutoff of 27.5 kg/m2 for metabolic surgery may be suitable for Chinese patients with T2DM.

Zhang|Ning-Jing|NJ| Fu|Yu-Zhe|YZ| Shan|Xiao-Dong|XD| Zhang|Ning|N| Sun|Xi-Tai|XT| Chu|Xue-Hui|XH| Bi|Yan|Y| Zhu|Da-Long|DL| Feng|Wen-Huan|WH|

Type 2 diabetes
Body mass index
Metabolic surgery


Electroanatomic voltage mapping and characterisation imaging for "right ventricle arrhythmic syndromes" beyond the arrhythmia definition: a comprehensive review.

Abstract: Three-dimensional (3D) reconstruction by means of electroanatomic mapping (EAM) systems, allows for the understanding of the mechanism of focal or re-entrant arrhythmic circuits along with pacing techniques. However, besides this conventional use, EAM may offer helpful anatomical and functional information. Data regarding electromechanical scar detection in ischaemic (and nonischaemic) cardiomyopathy are mostly consolidated, while emerging results are becoming available in contexts such as arrhythmogenic right ventricular dysplasia (ARVC/D) definition and Brugada syndrome. As part of an invasive procedure, EAM has not yet been widely adopted as a stand-alone tool in the diagnostic path. We aim to review the current literature regarding the use of 3D EAM systems for right ventricle (RV) functional characterisation beyond the definition of arrhythmia.

D019571:Arrhythmogenic Right Ventricular Dysplasia

Electroanatomic
Characterisation
Mapping for right ventricle


Phycobilisome integrity and functionality in lipid unsaturation and xanthophyll mutants in Synechocystis.

Abstract: The major light-harvesting system in cyanobacteria, the phycobilisome, is an essential component of the photosynthetic apparatus that regulates the utilization of the natural light source-the Sun. Earlier works revealed that the thylakoid membrane composition and its physical properties might have an important role in antennas docking. Polyunsaturated lipids and xanthophylls are among the most significant modulators of the physical properties of thylakoid membranes. In the nature, the action of these molecules is orchestrated in response to environmental stimuli among which the growth temperature is the most influential. In order to further clarify the significance of thylakoid membrane physical properties for the phycobilisomes assembly (i.e. structural integrity) and their ability to efficiently direct the excitation energy towards the photosynthetic complexes, in this work, we utilize cyanobacterial Synechocystis sp. PCC 6803 mutants deficient in polyunsaturated lipids (AD mutant) and xanthophylls (RO mutant), as well as a strain depleted of both xanthophylls and polyunsaturated lipids (ROAD multiple mutant). For the first time, we discuss the effect of those mutations on the phycobilisomes assembly, integrity and functionality at optimal (30 °C) and moderate low (25 °C) and high (35 °C) temperatures. Our results show that xanthophyll depletion exerts a much stronger effect on both phycobilisome's integrity and the response of cells to growth at suboptimal temperatures than lipid unsaturation level. The strongest effects were observed for the combined ROAD mutant, which exhibited thermally destabilized phycobilisomes and a population of energetically uncoupled phycocyanin units.

D045322:Photosynthetic Reaction Center Complex Proteins

Phycobilisome
Lipid unsaturation
Cyanobacteria
Carotenoids
Excitation energy transfer
Thermal stability


Injectable hydrogel as stem cell scaffolds from the thermosensitive terpolymer of NIPAAm/AAc/HEMAPCL.

Abstract: A series of biodegradable thermosensitive copolymers was synthesized by free radical polymerization with N-isopropylacrylamide (NIPAAm), acrylic acid (AAc) and macromer 2-hydroxylethyl methacrylate-poly(ɛ-caprolactone) (HEMAPCL). The structure and composition of the obtained terpolymers were confirmed by proton nuclear magnetic resonance spectroscopy, while their molecular weight was measured using gel permeation chromatography. The copolymers were dissolved in phosphate-buffered saline (PBS) solution (pH = 7.4) with different concentrations to prepare hydrogels. The lower critical solution temperature (LCST), cloud point, and rheological property of the hydrogels were determined by differential scanning calorimetry, ultraviolet-visible spectrometry, and rotational rheometry, respectively. It was found that LCST of the hydrogel increased significantly with the increasing NIPAAm content, and hydrogel with higher AAc/HEMAPCL ratio exhibited better storage modulus, water content, and injectability. The hydrogels were formed by maintaining the copolymer solution at 37°C. The degradation experiment on the formed hydrogels was conducted in PBS solution for 2 weeks and demonstrated a less than 20% weight loss. Scanning electron microscopy was also used to study the morphology of the hydrogel. The copolymer with NIPAAm/AAc/HEMAPCL ratio of 88:9.6:2.4 was bioconjugated with type I collagen for the purpose of biocompatibility enhancement. In-vitro cytotoxicity of the hydrogels both with and without collagen was also addressed.

Lian|Sheng|S| Xiao|Yan|Y| Bian|Qingqing|Q| Xia|Yu|Y| Guo|Changfa|C| Wang|Shenguo|S| Lang|Meidong|M|

biodegradable N-isopropylacrylamide bioreactive thermoresponsive


A Review about Regulatory Status and Recent Patents of Pharmaceutical Co-Crystals.

Abstract: Pharmaceutical Co-crystals are not new, they have gained much attention since the last decade among scientists and pharmaceutical industry. Pharmaceutical co-crystals are multicomponent systems composed of two or more molecules and held together by non-covalent interactions. The development of pharmaceutical co-crystals, a new solid crystalline form, offer superior physico-chemical properties (such as melting point, stability, solubility, permeability, bioavailability, taste masking, etc.) without altering the pharmacological properties. Recently, with the upsurge in the growth of Pharmaceutical co-crystals, the major concern is over the regulatory status of co-crystals. With the new guidelines from United States Food and Drug Administration (USFDA) and European Medicines Agency (EMA), the status has become even more complicated due to significantly different opinions. This review highlights whether co-crystals fulfil the requirements for the grant of a patent or not and how cocrystals are going to affect the present scenario of pharmaceuticals.

Patents
Pharmaceutical Co-crystals
Crystal Engineering
Regulatory guidelines


Massively parallel discovery of human-specific substitutions that alter enhancer activity.

Abstract: Genetic changes that altered the function of gene regulatory elements have been implicated in the evolution of human traits such as the expansion of the cerebral cortex. However, identifying the particular changes that modified regulatory activity during human evolution remain challenging. Here we used massively parallel enhancer assays in neural stem cells to quantify the functional impact of >32,000 human-specific substitutions in >4,300 human accelerated regions (HARs) and human gain enhancers (HGEs), which include enhancers with novel activities in humans. We found that >30% of active HARs and HGEs exhibited differential activity between human and chimpanzee. We isolated the effects of human-specific substitutions from background genetic variation to identify the effects of genetic changes most relevant to human evolution. We found that substitutions interacted in both additive and nonadditive ways to modify enhancer function. Substitutions within HARs, which are highly constrained compared to HGEs, showed smaller effects on enhancer activity, suggesting that the impact of human-specific substitutions is buffered in enhancers with constrained ancestral functions. Our findings yield insight into how human-specific genetic changes altered enhancer function and provide a rich set of candidates for studies of regulatory evolution in humans.

D000818:Animals
D005075:Biological Evolution
D004742:Enhancer Elements, Genetic
D015894:Genome, Human
D006801:Humans
D019579:Neocortex
D058953:Neural Stem Cells
D002679:Pan troglodytes
D014157:Transcription Factors

massively parallel enhancer assay
human accelerated regions
enhancer evolution
gene regulation
neurodevelopment


Histone methyltransferase SETDB1 promotes cells proliferation and migration by interacting withTiam1 in hepatocellular carcinoma.

Abstract:
BACKGROUND
SETDB1 is a histone H3K9 methyltransferase, which plays a significant role in the occurrence and progression of tumors. Previous studies have confirmed that T-lymphom invasion and metastasis gene (Tiam1) is a protein associated with the metastasis of hepatocellular carcinoma (HCC); however, we have not yet been successful in elucidating the specific mechanism of HCC.

METHODS
Yeast two-hybrid test was conducted to screen proteins that interacted with Tiam1 gene. Glutathione-S-transferase (GST) pull-down and crosslinking-immunoprecipitation (CLIP) assays were performed to determine whether SETDB1 can interact with Tiam1 gene. A series of related experiments were performed to explore role of SETDB1 on cell proliferation, migration, and invasion in HCC. Recovery experiment was performed to investigate the effect of Tiam1 knockdown on cell proliferation and migration, which was caused by SETDB1 overexpression in HCC cells. The expression of SETDB1 was frequently upregulated in HCC tissues and positively correlated with Tiam1.

RESULTS
GST pull-down and CLIP assays were performed to elucidate the interaction between SETDB1 and Tiam1. Cell proliferation, migration, and epithelial mesenchymal transformation (EMT) in HCC cells was promoted with the overexpression of SETDB1. Following the knockdown of Tiam1 gene, the effect of SETDB1 on cell proliferation and migration was reversed in HCC cells. The expression of SETDB1 was frequently up-regulated in HCC tissues, and it was positively correlated with Tiam1 gene.

CONCLUSIONS
Ours is the first study to prove that SETDB1 promotes the proliferation and migration of cells by forming SETDB1-Tiam1 compounds. We found that SETDB1-Tiam1 compounds were involved in a novel pathway, which regulated epigenetic modification of gene expression in HCC samples.

D015972:Gene Expression Regulation, Neoplastic

D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1

D023041:Xenograft Model Antitumor Assays