With high extinction coefficients and long absorption wavelengths in the near infrared region, phthalocyanines (Pcs) and naphthalocyanines (Ncs) are well-suited for optical imaging and phototherapies in biological tissues. Pcs and Ncs have been used in a range of theranostic applications. Peripheral and axial substituents can be introduced to Pcs and Ncs for chemical modification. Seamless metal chelation of Pcs or Ncs can expand their possibilities as medical therapeutic and imaging agents. Nanoparticulate approaches enable unique ways to deliver Pcs and Ncs to target tissues and improve their solubility, biocompatibility, biodistribution and stability. Herein, we highlight some recent Pc or Nc nanoscale systems for theranostic applications. WIREs Nanomed Nanobiotechnol 2017, 9:e1420. doi: 10.1002/wnan.1420 For further resources related to this article, please visit the WIREs website.

Recent studies have yielded initial evidence for an association between Internet Use Disorder (IUD), empathy, and life satisfaction. In the present study we sought to replicate these previous findings, and then to extend this research by also examining the relationship between empathy, life satisfaction, and the related phenomenon of Smartphone Use Disorder (SUD). The present study included independent samples from China (N = 612, 162 females) and Germany (N = 304, 207 females), with the same set of questionnaires administered to both samples. IUD was measured with Pawlikowski's s-IAT and SUD was assessed with the short version of Kwon's Smartphone Addiction Scale. The Interpersonal Reactivity Index (IRI) was used to assess individual differences in empathy. Please note that for the German sample data on the empathy quotient (EQ) are also available. Life satisfaction data were collected using items from the SOEP-Questionnaire (Socio-Economic Panel, Germany). In both of our samples we replicated previous findings showing the association between higher IUD, lower empathy, and lower life satisfaction scores. In addition, individuals with higher SUD showed higher scores on the IRI Personal Distress scale in China and Germany, while further associations between IRI dimensions and SUD were only found in the Chinese sample. Personal Distress is known to be highly correlated with the personality trait of Neuroticism, hence higher stress/negative emotionality in tense social situations is related to SUD. In the present study we confirm earlier findings showing the relationship between empathy, life satisfaction, and IUD, and extend some of these findings to SUD. We also emphasize the importance of cross-cultural studies when investigating IUD/SUD in the context of empathy and life satisfaction.

BACKGROUND

Dysmenorrhoea may begin soon after the menarche, after which it often improves with age, or it may originate later in life after the onset of an underlying causative condition. Dysmenorrhoea is common, and in up to 20% of women it may be severe enough to interfere with daily activities.

METHODS

We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for primary dysmenorrhoea? We searched: Medline, Embase, The Cochrane Library, and other important databases up to January 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

RESULTS

We found 35 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.

CONCLUSIONS

In this systematic review we present information relating to the effectiveness and safety of the following interventions: acupressure, acupuncture, aspirin, behavioural interventions, contraceptives (combined oral), fish oil, herbal remedies, magnets, non-steroidal anti-inflammatory drugs, paracetamol, progestogens (intrauterine), spinal manipulation, surgical interruption of pelvic nerve pathways, thiamine, toki-shakuyaku-san, topical heat, transcutaneous electrical nerve stimulation (TENS), vitamin B12, and vitamin E.

To establish a valid database of vocal emotional stimuli in Mandarin Chinese, a set of Chinese pseudosentences (i.e., semantically meaningless sentences that resembled real Chinese) were produced by four native Mandarin speakers to express seven emotional meanings: anger, disgust, fear, sadness, happiness, pleasant surprise, and neutrality. These expressions were identified by a group of native Mandarin listeners in a seven-alternative forced choice task, and items reaching a recognition rate of at least three times chance performance in the seven-choice task were selected as a valid database and then subjected to acoustic analysis. The results demonstrated expected variations in both perceptual and acoustic patterns of the seven vocal emotions in Mandarin. For instance, fear, anger, sadness, and neutrality were associated with relatively high recognition, whereas happiness, disgust, and pleasant surprise were recognized less accurately. Acoustically, anger and pleasant surprise exhibited relatively high mean f0 values and large variation in f0 and amplitude; in contrast, sadness, disgust, fear, and neutrality exhibited relatively low mean f0 values and small amplitude variations, and happiness exhibited a moderate mean f0 value and f0 variation. Emotional expressions varied systematically in speech rate and harmonics-to-noise ratio values as well. This validated database is available to the research community and will contribute to future studies of emotional prosody for a number of purposes. To access the database, please contact pan.liu@mail.mcgill.ca.

Please cite this paper as: Aldo-keto reductase 1C subfamily genes in skin are UV-inducible: possible role in keratinocytes survival. Experimental Dermatology 2009; 18: 611-618.Abstract: Human skin is endowed with the capacity to synthesize and metabolize steroid hormones, a function of importance in skin physiology and pathology. It is the hormone-regulatory enzymes, including the aldo-keto reductase 1C subfamily (AKR1Cs) that are largely responsible for the local levels of active steroid hormones. AKR1C1 and AKR1C2 inactivate progesterone and 5alpha-dihydrotestosterone, respectively, whereas AKR1C3 activates oestradiol and testosterone. Here, we show that AKR1C1-3 are expressed in keratinocytes and fibroblasts, with marginal expression in melanocytes. In human primary keratinocytes, AKR1C1 and -2 were UVB-inducible in a dose-dependent manner, as shown by quantitative PCR and Western blot analyses. The induction of AKR1C1 by UVB was concomitant with the presence of an apoptotic marker, the cleavage product of poly-ADP ribose polymerase. Similarly, the activation of AKR1C1 and -2 upon UVB exposure was demonstrated in swine skin in vivo and in human skin explants. As expected, hydrogen peroxide-derived reactive oxygen species also induced AKR1C1 and -2 mRNA and protein levels in keratinocytes in a dose-dependent manner. Furthermore, down-regulation of AKR1Cs by small interfering ribonucleic acid led to significantly reduced cell viability. Based on the combined evidence of the presence of an apoptotic marker in the UVB-exposed keratinocytes with increased AKR1Cs expression and reduced cell viability in down-regulated AKR1Cs, we suggest that AKR1C subfamily genes are stress-inducible and might function as survival factors in keratinocytes.

The behavior change technique taxonomy v1 (BCTTv1; Michie and colleagues, 2013) is a comprehensive tool to characterize active ingredients of interventions and includes 93 labels that are hierarchically clustered into 16 hierarchical clusters.

The aim of this study was to identify the active ingredients in electronic health (eHealth) interventions targeting patients with poorly controlled type 2 diabetes mellitus (T2DM) and relevant outcomes.

We conducted a scoping review using the BCTTv1. Randomized controlled trials (RCTs), studies with or pre-post-test designs, and quasi-experimental studies examining efficacy and effectiveness of eHealth interventions for disease management or the promotion of relevant health behaviors were identified by searching PubMed, Web of Science, and PsycINFO. Reviewers independently screened titles and abstracts for eligibility using predetermined eligibility criteria. Data were extracted following a data extraction sheet. The BCTTv1 was used to characterize active ingredients of the interventions reported in the included studies.

Of the 1404 unique records screened, 32 studies fulfilled the inclusion criteria and reported results on the efficacy and or or effectiveness of interventions. Of the included 32 studies, 18 (56%) were Web-based interventions delivered via personal digital assistant (PDA), tablet, computer, and/or mobile phones; 7 (22%) were telehealth interventions delivered via landline; 6 (19%) made use of text messaging (short service message, SMS); and 1 employed videoconferencing (3%). Of the 16 hierarchical clusters of the BCTTv1, 11 were identified in interventions included in this review. Of the 93 individual behavior change techniques (BCTs), 31 were identified as active ingredients of the interventions. The most common BCTs identified were instruction on how to perform behavior, adding objects to the environment, information about health consequences, self-monitoring of the outcomes and/or and prefers to be explicit to avoid ambiguity. Response: Checked and avoided of a certain behavior Author: Please note that the journal discourages the use of parenthesis to denote either and/or and prefers to be explicit to avoid ambiguity. Response: Checked and avoided "and/or" and prefers to be explicit to avoid ambiguity. Response: Checked and avoided, and feedback on outcomes of behavior.

Our results suggest that the majority of BCTs employed in interventions targeting persons with T2DM revolve around the promotion of self-regulatory behavior to manage the disease or to assist patients in performing health behaviors necessary to prevent further complications of the disease. Detailed reporting of the BCTs included in interventions targeting this population may facilitate the replication and further investigation of such interventions.

BACKGROUND

Gestational diabetes mellitus (GDM) is increasing and is a risk for type 2 diabetes. Evidence supporting screening comes mostly from high-income countries. We aimed to determine prevalence and outcomes in urban Viet Nam. We compared the proposed International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criterion, requiring one positive value on the 75-g glucose tolerance test, to the 2010 American Diabetes Association (ADA) criterion, requiring two positive values.

RESULTS

We conducted a prospective cohort study in Ho Chi Minh City, Viet Nam. Study participants were 2,772 women undergoing routine prenatal care who underwent a 75-g glucose tolerance test and interview around 28 (range 24-32) wk. GDM diagnosed by the ADA criterion was treated by local protocol. Women with GDM by the IADPSG criterion but not the ADA criterion were termed "borderline" and received standard care. 2,702 women (97.5% of cohort) were followed until discharge after delivery. GDM was diagnosed in 164 participants (6.1%) by the ADA criterion, 550 (20.3%) by the IADPSG criterion. Mean body mass index was 20.45 kg/m(2) in women with out GDM, 21.10 in women with borderline GDM, and 21.81 in women with GDM, p<0.001. Women with GDM and borderline GDM were more likely to deliver preterm, with adjusted odds ratios (aORs) of 1.49 (95% CI 1.16-1.91) and 1.52 (1.03-2.24), respectively. They were more likely to have clinical neonatal hypoglycaemia, aORs of 4.94 (3.41-7.14) and 3.34 (1.41-7.89), respectively. For large for gestational age, the aORs were 1.16 (0.93-1.45) and 1.31 (0.96-1.79), respectively. There was no significant difference in large for gestational age, death, severe birth trauma, or maternal morbidity between the groups. Women with GDM underwent more labour inductions, aOR 1.51 (1.08-2.11).

CONCLUSIONS

Choice of criterion greatly affects GDM prevalence in Viet Nam. Women with GDM by the IADPSG criterion were at risk of preterm delivery and neonatal hypoglycaemia, although this criterion resulted in 20% of pregnant women being positive for GDM. The ability to cope with such a large number of cases and prevent associated adverse outcomes needs to be demonstrated before recommending widespread screening. Please see later in the article for the Editors' Summary.

In spite of the high metabolic cost of cellular production, the brain contains only a fraction of the neurons generated during embryonic development. In the rodent cerebral cortex, a first wave of programmed cell death surges at embryonic stages and affects primarily progenitor cells. A second, larger wave unfolds during early postnatal development and ultimately determines the final number of cortical neurons. Programmed cell death in the developing cortex is particularly dependent on neuronal activity and unfolds in a cell-specific manner with precise temporal control. Pyramidal cells and interneurons adjust their numbers in sync, which is likely crucial for the establishment of balanced networks of excitatory and inhibitory neurons. In contrast, several other neuronal populations are almost completely eliminated through apoptosis during the first two weeks of postnatal development, highlighting the importance of programmed cell death in sculpting the mature cerebral cortex. Expected final online publication date for the Annual Review of Cell and Developmental Biology Volume 35 is October 7, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Background: Convalescent plasma and hyperimmune immunoglobulin may reduce mortality in patients with viral respiratory diseases, and are being investigated as potential therapies for coronavirus disease 2019 (COVID-19). A thorough understanding of the current body of evidence regarding benefits and risks of these interventions is required. OBJECTIVES: Using a living systematic review approach, to assess whether convalescent plasma or hyperimmune immunoglobulin transfusion is effective and safe in the treatment of people with COVID-19; and to maintain the currency of the evidence.

Search methods: To identify completed and ongoing studies, we searched the World Health Organization (WHO) COVID-19 Global literature on coronavirus disease Research Database, MEDLINE, Embase, the Cochrane COVID-19 Study Register, the Epistemonikos COVID-19 L*OVE Platform, and trial registries. Searches were done on 17 March 2021.

Selection criteria: We included randomised controlled trials (RCTs) evaluating convalescent plasma or hyperimmune immunoglobulin for COVID-19, irrespective of disease severity, age, gender or ethnicity. For safety assessments, we also included non-controlled non-randomised studies of interventions (NRSIs) if 500 or more participants were included. We excluded studies that included populations with other coronavirus diseases (severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS)), as well as studies evaluating standard immunoglobulin.

Data collection and analysis: We followed standard Cochrane methodology. To assess bias in included studies, we used the Cochrane 'Risk of Bias 2' tool for RCTs, and for NRSIs, the assessment criteria for observational studies, provided by Cochrane Childhood Cancer. We rated the certainty of evidence, using the GRADE approach, for the following outcomes: all-cause mortality, improvement and worsening of clinical status (for individuals with moderate to severe disease), development of severe clinical COVID-19 symptoms (for individuals with asymptomatic or mild disease), quality of life (including fatigue and functional independence), grade 3 or 4 adverse events, and serious adverse events.

Main results: We included 13 studies (12 RCTs, 1 NRSI) with 48,509 participants, of whom 41,880 received convalescent plasma. We did not identify any completed studies evaluating hyperimmune immunoglobulin. We identified a further 100 ongoing studies evaluating convalescent plasma or hyperimmune immunoglobulin, and 33 studies reporting as being completed or terminated. Individuals with a confirmed diagnosis of COVID-19 and moderate to severe disease Eleven RCTs and one NRSI investigated the use of convalescent plasma for 48,349 participants with moderate to severe disease. Nine RCTs compared convalescent plasma to placebo treatment or standard care alone, and two compared convalescent plasma to standard plasma (results not included in abstract). Effectiveness of convalescent plasma We included data on nine RCTs (12,875 participants) to assess the effectiveness of convalescent plasma compared to placebo or standard care alone. Convalescent plasma does not reduce all-cause mortality at up to day 28 (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.92 to 1.05; 7 RCTs, 12,646 participants; high-certainty evidence). It has little to no impact on clinical improvement for all participants when assessed by liberation from respiratory support (RR not estimable; 8 RCTs, 12,682 participants; high-certainty evidence). It has little to no impact on the chance of being weaned or liberated from invasive mechanical ventilation for the subgroup of participants requiring invasive mechanical ventilation at baseline (RR 1.04, 95% CI 0.57 to 1.93; 2 RCTs, 630 participants; low-certainty evidence). It does not reduce the need for invasive mechanical ventilation (RR 0.98, 95% CI 0.89 to 1.08; 4 RCTs, 11,765 participants; high-certainty evidence). We did not identify any subgroup differences. We did not identify any studies reporting quality of life, and therefore, do not know whether convalescent plasma has any impact on quality of life. One RCT assessed resolution of fatigue on day 7, but we are very uncertain about the effect (RR 1.21, 95% CI 1.02 to 1.42; 309 participants; very low-certainty evidence). Safety of convalescent plasma We included results from eight RCTs, and one NRSI, to assess the safety of convalescent plasma. Some of the RCTs reported on safety data only for the convalescent plasma group. We are uncertain whether convalescent plasma increases or reduces the risk of grade 3 and 4 adverse events (RR 0.90, 95% CI 0.58 to 1.41; 4 RCTs, 905 participants; low-certainty evidence), and serious adverse events (RR 1.24, 95% CI 0.81 to 1.90; 2 RCTs, 414 participants; low-certainty evidence). A summary of reported events of the NRSI (reporting safety data for 20,000 of 35,322 transfused participants), and four RCTs reporting safety data only for transfused participants (6125 participants) are included in the full text. Individuals with a confirmed diagnosis of SARS-CoV-2 infection and asymptomatic or mild disease We identified one RCT reporting on 160 participants, comparing convalescent plasma to placebo treatment (saline). Effectiveness of convalescent plasma We are very uncertain about the effect of convalescent plasma on all-cause mortality (RR 0.50, 95% CI 0.09 to 2.65; very low-certainty evidence). We are uncertain about the effect of convalescent plasma on developing severe clinical COVID-19 symptoms (RR not estimable; low-certainty evidence). We identified no study reporting quality of life. Safety of convalescent plasma We do not know whether convalescent plasma is associated with a higher risk of grade 3 or 4 adverse events (very low-certainty evidence), or serious adverse events (very low-certainty evidence). This is a living systematic review. We search weekly for new evidence and update the review when we identify relevant new evidence. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.

Authors' conclusions: We have high certainty in the evidence that convalescent plasma for the treatment of individuals with moderate to severe disease does not reduce mortality and has little to no impact on measures of clinical improvement. We are uncertain about the adverse effects of convalescent plasma. While major efforts to conduct research on COVID-19 are being made, heterogeneous reporting of outcomes is still problematic. There are 100 ongoing studies and 33 studies reporting in a study registry as being completed or terminated. Publication of ongoing studies might resolve some of the uncertainties around hyperimmune immunoglobulin therapy for people with any disease severity, and convalescent plasma therapy for people with asymptomatic or mild disease.

Trial registration: ClinicalTrials.gov NCT04356534 NCT04345523 NCT04346446 NCT04342182 NCT04530370 NCT04381936 NCT04338360 NCT04479163 NCT04359810 NCT04383535 NCT04392414 NCT04375098 NCT04434131 NCT04343261 NCT04340050 NCT04357106 NCT04321421 NCT04441424 NCT04381858 NCT04344535 NCT04494984.

BACKGROUND

Herniated lumbar disc is a displacement of disc material (nucleus pulposus or annulus fibrosis) beyond the intervertebral disc space. The highest prevalence is among people aged 30-50 years, with a male to female ratio of 2:1. There is little evidence to suggest that drug treatments are effective in treating herniated disc.

METHODS

We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments, non-drug treatments, and surgery for herniated lumbar disc? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2008 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

RESULTS

We found 49 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.

CONCLUSIONS

In this systematic review, we present information relating to the effectiveness and safety of the following interventions: acupuncture, advice to stay active, analgesics, antidepressants, bed rest, corticosteroids (epidural injections), cytokine inhibitors (infliximab), discectomy (automated percutaneous, laser, microdisectomy, standard), exercise therapy, heat, ice, massage, muscle relaxants, non-steroidal anti-inflammatory drugs (NSAIDs), percutaneous disc decompression, spinal manipulation, and traction.

Music is a highly versatile form of art and communication that has been an essential part of human society since its early days. Neuroimaging studies indicate that music is a powerful stimulus also for the human brain, engaging not just the auditory cortex but also a vast, bilateral network of temporal, frontal, parietal, cerebellar, and limbic brain areas that govern auditory perception, syntactic and semantic processing, attention and memory, emotion and mood control, and motor skills. Studies of amusia, a severe form of musical impairment, highlight the right temporal and frontal cortices as the core neural substrates for adequate perception and production of music. Many of the basic auditory and musical skills, such as pitch and timbre perception, start developing already in utero, and babies are born with a natural preference for music and singing. Music has many important roles and functions throughout life, ranging from emotional self-regulation, mood enhancement, and identity formation to promoting the development of verbal, motor, cognitive, and social skills and maintaining their healthy functioning in old age. Music is also used clinically as a part of treatment in many illnesses, which involve affective, attention, memory, communication, or motor deficits. Although more research is still needed, current evidence suggests that music-based rehabilitation can be effective in many developmental, psychiatric, and neurological disorders, such as autism, depression, schizophrenia, and stroke, as well as in many chronic somatic illnesses that cause pain and anxiety. WIREs Cogn Sci 2013, 4:441-451. doi: 10.1002/wcs.1237 The authors have declared no conflicts of interest for this article. For further resources related to this article, please visit the WIREs website.

Precision medicine is the future of health care: please watch the animation at https://vimeo.com/241154708 . As a technology-intensive and -dependent medical discipline, oncology will be at the vanguard of this impending change. However, to bring about precision medicine, a fundamental conundrum must be solved: Human cognitive capacity, typically constrained to five variables for decision making in the context of the increasing number of available biomarkers and therapeutic options, is a limiting factor to the realization of precision medicine. Given this level of complexity and the restriction of human decision making, current methods are untenable. A solution to this challenge is multifactorial decision support systems (DSSs), continuously learning artificial intelligence platforms that integrate all available data-clinical, imaging, biologic, genetic, cost-to produce validated predictive models. DSSs compare the personalized probable outcomes-toxicity, tumor control, quality of life, cost effectiveness-of various care pathway decisions to ensure optimal efficacy and economy. DSSs can be integrated into the workflows both strategically (at the multidisciplinary tumor board level to support treatment choice, eg, surgery or radiotherapy) and tactically (at the specialist level to support treatment technique, eg, prostate spacer or not). In some countries, the reimbursement of certain treatments, such as proton therapy, is already conditional on the basis that a DSS is used. DSSs have many stakeholders-clinicians, medical directors, medical insurers, patient advocacy groups-and are a natural consequence of big data in health care. Here, we provide an overview of DSSs, their challenges, opportunities, and capacity to improve clinical decision making, with an emphasis on the utility in oncology.

Senescence is the consequence of a signaling mechanism activated in stressed cells to prevent proliferation of cells with damage. Senescent cells (Sncs) often develop a senescence-associated secretory phenotype to prompt immune clearance, which drives chronic sterile inflammation and plays a causal role in aging and age-related diseases. Sncs accumulate with age and at anatomical sites of disease. Thus, they are regarded as a logical therapeutic target. Senotherapeutics are a new class of drugs that selectively kill Sncs (senolytics) or suppress their disease-causing phenotypes (senomorphics/senostatics). Since 2015, several senolytics went from identification to clinical trial. Preclinical data indicate that senolytics alleviate disease in numerous organs, improve physical function and resilience, and suppress all causes of mortality, even if administered to the aged. Here, we review the evidence that Sncs drive aging and disease, the approaches to identify and optimize senotherapeutics, and the current status of preclinical and clinical testing of senolytics. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 61 is January 7, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

OBJECTIVE

The authors sought to evaluate the relative performance of a drug-eluting balloon (DEB) and a drug-eluting stent (DES) in patients with any (bare-metal or drug-eluting stent) in-stent restenosis (ISR).

BACKGROUND

The treatment of ISR remains challenging in contemporary clinical practice.

METHODS

In a multicenter randomized noninferiority trial, patients with any ISR were randomly allocated in a 1:1 fashion to treatment with a DEB (SeQuent Please paclitaxel-eluting balloon, B. Braun Melsungen, Melsungen, Germany), or a DES (XIENCE everolimus-eluting stent, Abbott Vascular, Santa Clara, California). The primary endpoint was noninferiority in terms of in-segment minimal lumen diameter (MLD) at 6-month angiographic follow-up. Secondary endpoints included angiographic parameters at 6 months and clinical follow-up up to 12 months.

RESULTS

A total of 278 patients, of whom 56% had DES-ISR, were randomized at 8 sites to treatment with DEB (n = 141) or DES (n = 137). As compared with DEB, DES was associated with larger MLD and lower % stenosis immediately post-procedure (1.84 ± 0.46 vs. 1.72 ± 0.35; p = 0.018; and 26 ± 10% vs. 30 ± 10%; p = 0.03). Angiographic follow up was completed at 196 ± 53 days in 79% of patients. With respect to the primary endpoint of in-segment MLD at 6 months, DEB was noninferior to DES (DEB 1.71 ± 0.51 mm vs. DES 1.74 ± 0.61 mm; p for noninferiority <0.0001). Target vessel revascularization at 12-month follow-up was similar in both groups (DES 7.1% vs. DEB 8.8%; p = 0.65).

CONCLUSIONS

In patients with ISR, treatment with DEB was noninferior compared with DES in terms of 6-month MLD. There were no differences in clinical endpoints, including target vessel revascularization up to 12 months. Therefore, use of a DEB is an attractive treatment option for in-stent restenosis, withholding the need for additional stent implantation.

Ion channels and G protein-coupled receptors (GPCRs) are regulated by lipids in their membrane environment. Structural studies combined with biophysical and molecular simulation investigations reveal interaction sites for specific lipids on membrane protein structures. For K channels, PIP₂ plays a key role in regulating Kv and Kir channels. Likewise, several recent cryo-EM structures of TRP channels have revealed bound lipids, including PIP₂ and cholesterol. Among the pentameric ligand-gated ion channel family, structural and biophysical studies suggest the M4 TM helix may act as a lipid sensor, e.g., forming part of the binding sites for neurosteroids on the GABA_A receptor. Structures of GPCRs have revealed multiple cholesterol sites, which may modulate both receptor dynamics and receptor oligomerization. PIP₂ also interacts with GPCRs and may modulate their interactions with G proteins. Overall, it is evident that multiple lipid-binding sites exist on channels and receptors that modulate their function allosterically and are potential druggable sites. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 60 is January 6, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Comparative physiology studies of high-altitude species provide an exceptional opportunity to understand naturally evolved mechanisms of hypoxia resistance. Aerobic capacity (VO2max) is a critical performance trait under positive selection in some high-altitude taxa, and several high-altitude natives have evolved to resist the depressive effects of hypoxia on VO2max. This is associated with enhanced flux capacity through the O2 transport cascade and attenuation of the maladaptive responses to chronic hypoxia that can impair O2 transport. Some highlanders exhibit elevated rates of carbohydrate oxidation during exercise, taking advantage of its high ATP yield per mole of O2. Certain highland native animals have also evolved more oxidative muscles and can sustain high rates of lipid oxidation to support thermogenesis. The underlying mechanisms include regulatory adjustments of metabolic pathways and to gene expression networks. Therefore, the evolution of hypoxia resistance in high-altitude natives involves integrated functional changes in the pathways for O2 and substrate delivery and utilization by mitochondria. Expected final online publication date for the Annual Review of Physiology Volume 81 is February 10, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

BACKGROUND

The Magpie Trial compared magnesium sulfate with placebo for women with preeclampsia. The objective of this study was to explore women's views and experiences of participating in the Magpie Trial in the United Kingdom.

METHODS

Postal questionnaires were sent to 771 women participants in the Magpie Trial to assess long-term health of UK women and children. The questionnaire included three questions exploring women's experience of participating in the trial: (a) If time suddenly went backward, and you had to do it all over again, would you agree to participate in the Magpie Trial? (b) Please tell us if there was anything about the Magpie Trial that you think could have been done better; and (c) Please tell us if there was anything about the Magpie Trial, or your experience of joining the trial, that you think was particularly good.

RESULTS

Overall, 619 of the 771 women who were sent questionnaires returned them. In response to the three questions: (a) 58 percent (356) of women responded "definitely yes," 27 percent (169) "probably yes," 4 percent (23) "probably no," 5 percent (33) "definitely no," and 5 percent (34) "not sure." No clear evidence was shown of a relationship with allocated treatment, although women who responded "probably or definitely no" were more likely to have had side effects from trial treatment. (b) Although 44 percent of women stated that nothing could have been done better, free text suggestions related to content of recruitment information, and its timing, and wanting to know treatment allocation and trial results. c) Women were generally extremely positive about being followed up and receiving trial results.

CONCLUSIONS

Women were largely positive about participation in the trial and its follow-up, but still reported ways they believed the study could have been improved, such as more information, given earlier, which also has implications for clinical care.

Patient Blood Management is the timely application of evidence-based medical and surgical concepts designed to maintain hemoglobin concentration, optimize hemostasis, and minimize blood loss to improve patient outcomes. Conceptually similar to a "bundle" strategy, it is designed to improve clinical care using comprehensive evidence-based treatment strategies to manage patients with potential or ongoing critical bleeding, bleeding diathesis, critical anemia, and/ or a coagulopathy. Patient Blood Management includes multimodal strategies to screen, diagnose and properly treat anemia, coagulopathies and minimize bleeding, using goal-directed therapy and leverages a patient's physiologic ability to adapt to anemia while definitive treatment is undertaken. Allogeneic blood component transfusion is one traditional therapeutic modality out of many for managing blood loss and anemia and, while it may be the best choice in certain situations, other effective and more appropriate options are available and should be used in conjunction or alone. Therefore, comprehensive Patient Blood Management is the new standard of care to prevent and manage anemia and optimize hemostasis and has been recommended by the World Health Organization, the American Society of Anesthesiologists, the European Society of Anaesthesiology and the Australian National Blood Authority. While there is a plethora of expert consensus and good practice guidelines published for blood component transfusion from multiple professional organizations and societies, there remains a need for more comprehensive and broader standards of patient medical management to proactively reduce the risk of exposure to allogeneic transfusions. In 2010, the Society for Advancement of Blood Management published the first comprehensive standards to address the administrative and clinical components of an effective, patient-centered Patient Blood Management program. Recognizing the need to reduce inappropriate transfusions, some professional organizations have placed their emphasis on transfusion guidelines. In contrast, the focus of the Society for Advancement of Blood Management Standard is on the centrality of the patient and the full spectrum of therapeutic strategies needed to improve clinical outcomes in patients at risk for blood loss or anemia, thereby reducing avoidable transfusions as well. The Standards are meant not to replace, but to complement transfusion guidelines by more completely addressing the need for a multi-modal clinical approach with the goal to improve patient outcomes. Compared to adult programs, Pediatric Patient Blood Management programs are currently not commonly accepted as standard of care for pediatric patients. This is partly due to the fact that, until recently, there was a paucity of robust evidence-based literature and expert consensus guidelines on pediatric PBM. Managing pediatric bleeding and blood product transfusion presents a unique set of challenges. The main goal of transfusion is to correct or avoid imminent inadequate oxygen carrying capacity caused by inadequate red blood cell mass. Determining when, what, and how much to transfuse can be difficult. Neonates, infants, children, and adolescents each have specific considerations based on age, weight, physiology, and pharmacology. In this edition of Pediatric Anaesthesia we provide, in abbreviated format, the 4th edition of the Administrative and Clinical Standards for Patient Blood Management; Pediatric Version, first published in 2010 with the addition of a new Pediatric section in 2016. These Standards provide guidance for implementing a comprehensive Pediatric Patient Blood Management program at both pediatric and adult medical institutions. While every hospital may not be equipped to have a dedicated Pediatric Patient Blood Management program, this document highlights important universal clinical strategies that can be implemented to optimize pediatric bleeding management and minimize allogeneic blood product exposure through the use of multi-modal therapeutic strategies that have their central emphasis on the patient rather than the transfusion. Important strategies include: treatment of preoperative anemia, standardized transfusion algorithms, the use of restrictive transfusion thresholds, goal-directed therapy based on point of care and viscoelastic testing, antifibrinolytics, and avoidance of hemodilution and hypothermia as supported by evidence. For the full version, please go to https://www.sabm.org/publications.

Cooking is one of the basic activities in our lives. However, people frequently feel they fall short of time to cook when facing problems with the temporal organization of daily life. How people think about home cooking is considered to be important for the time they spend on preparing meals. It is assumed that the meaning of cooking differs for different people, depending on the temporal and social context. This contribution allows us to clarify how the meaning of cooking varies according to individual and household characteristics and the cooking occasion. By using the pooled time-diary data from the Flemish time-use surveys from 1999 and 2004 we can examine people's views on cooking in order to understand how people use time for food preparation. Although the results suggest that people consider cooking primarily as a household chore, preparing food can also be a way to please others, as well as themselves. It seems that feelings of time pressure and the family situation are clearly related to men's and women's cooking experiences. Furthermore, the meaning of cooking also tends to be clearly influenced by the meal situation and (the moment of) the day.

The nucleolus of mammalian cells contains hundreds of box C/D small nucleolar RNAs (SNORDs). Through their ability to base pair with ribosomal RNA precursors, most play important roles in the synthesis and/or activity of ribosomes, either by guiding sequence-specific 2'-O-methylations or by facilitating RNA folding and cleavages. A growing number of SNORD genes with elusive functions have been discovered recently. Intriguingly, the vast majority of them are located in two large, imprinted gene clusters at human chromosome region 15q11q13 (the SNURF-SNRPN domain) and at 14q32 (the DLK1-DIO3 domain) where they are expressed, respectively, only from the paternally and maternally inherited alleles. These placental mammal-specific SNORD genes have many features of the canonical SNORDs that guide 2'-O-methylations, yet they lack obvious complementarity with ribosomal RNAs and, surprisingly, they are processed from large, tandemly repeated genes expressed preferentially in the brain. This review summarizes our understanding of the biology of these peculiar SNORD genes, focusing particularly on SNORD115 and SNORD116 in the SNURF-SNRPN domain. It examines the growing evidence that altered levels of these SNORDs and/or their host-gene transcripts may be a primary cause of Prader-Willi syndrome (PWS; a rare disorder characterized by overeating and obesity) as well as abnormalities in signaling through the 5-HT2C serotonin receptor. Finally, the hypothesis that PWS may be a ribosomopathy (ribosomal disease) is also discussed. WIREs RNA 2017, 8:e1417. doi: 10.1002/wrna.1417 For further resources related to this article, please visit the WIREs website.

Mechanobiology, the study of the influence of mechanical loads on biological processes through signaling to cells, is fundamental to the inherent ability of bone tissue to adapt its structure in response to mechanical stimulation. The immense contribution of computational modeling to the nascent field of bone mechanobiology is indisputable, having aided in the interpretation of experimental findings and identified new avenues of inquiry. Indeed, advances in computational modeling have spurred the development of this field, shedding new light on problems ranging from the mechanical response to loading by individual cells to tissue differentiation during events such as fracture healing. To date, in silico bone mechanobiology has generally taken a reductive approach in attempting to answer discrete biological research questions, with research in the field broadly separated into two streams: (1) mechanoregulation algorithms for predicting mechanobiological changes to bone tissue and (2) models investigating cell mechanobiology. Future models will likely take advantage of advances in computational power and techniques, allowing multiscale and multiphysics modeling to tie the many separate but related biological responses to loading together as part of a larger systems biology approach to shed further light on bone mechanobiology. Finally, although the ever-increasing complexity of computational mechanobiology models will inevitably move the field toward patient-specific models in the clinic, the determination of the context in which they can be used safely for clinical purpose will still require an extensive combination of computational and experimental techniques applied to in vitro and in vivo applications. WIREs Syst Biol Med 2016, 8:485-505. doi: 10.1002/wsbm.1356 For further resources related to this article, please visit the WIREs website.

Although viruses comprise the most abundant genetic material in the biosphere, to date only several thousand virus species have been formally defined. Such a limited perspective on virus diversity has in part arisen because viruses were traditionally considered only as etiologic agents of overt disease in humans or economically important species and were often difficult to identify using cell culture. This view has dramatically changed with the rise of metagenomics, which is transforming virus discovery and revealing a remarkable diversity of viruses sampled from diverse cellular organisms. These newly discovered viruses help fill major gaps in the evolutionary history of viruses, revealing a near continuum of diversity among genera, families, and even orders of RNA viruses. Herein, we review some of the recent advances in our understanding of the RNA virosphere that have stemmed from metagenomics, note future directions, and highlight some of the remaining challenges to this rapidly developing field. Expected final online publication date for the Annual Review of Virology Volume 6 is September 30, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.