Search Results (25)

Newborn screening for cystic fibrosis (CF) has been universal in the US since 2010; however, there is significant variation among newborn screening algorithms. Systematic reviews were used to develop seven recommendations for newborn screening program practices to improve timeliness, sensitivity, and equity in diagnosing infants with CF: (1) The CF Foundation recommends the use of a floating immunoreactive trypsinogen (IRT) cutoff over a fixed IRT cutoff; (2) The CF Foundation recommends using a very high IRT referral strategy in CF newborn screening programs whose variant panel does not include all CF-causing variants in CFTR2 or does not have a variant panel that achieves at least 95% sensitivity in all ancestral groups within the state; (3) The CF Foundation recommends that CF newborn screening algorithms should not limit CFTR variant detection to the F508del variant or variants included in the American College of Medical Genetics-23 panel; (4) The CF Foundation recommends that CF newborn screening programs screen for all CF-causing CFTR variants in CFTR2; (5) The CF Foundation recommends conducting CFTR variant screening twice weekly or more frequently as resources allow; (6) The CF Foundation recommends the inclusion of a CFTR sequencing tier following IRT and CFTR variant panel testing to improve the specificity and positive predictive value of CF newborn screening; (7) The CF Foundation recommends that both the primary care provider and the CF specialist be notified of abnormal newborn screening results. Through implementation, it is anticipated that these recommendations will result in improved sensitivity, equity, and timeliness of CF newborn screening, leading to improved health outcomes for all individuals diagnosed with CF following newborn screening and a decreased burden on families. Full article

Enteric infections due to viral pathogens are a major public health concern. Detecting the risk areas requires a strong surveillance system for pathogenic viruses in sources such as wastewater. Towards building an environmental surveillance system in Zambia, we aimed to identify group A rotavirus (RVA) and human adenovirus (HAdV) in wastewater. Convenient sampling was conducted at four study sites every Tuesday for five consecutive weeks. The research team focused on three different methods of viral concentration to determine the suitability in terms of cost and applicability for a regular surveillance system: the bag-mediated filtration system (BMFS), polyethylene glycol-based (PEG) precipitation, and skimmed milk (SM) flocculation. We screened 20 wastewater samples for HAdV and RVA using quantitative polymerase chain reaction (qPCR) and conventional polymerase chain reaction (cPCR). Of the 20 samples tested using qPCR, 18/20 (90%) tested positive for HAdV and 14/20 (70%) tested positive for RVA. For the genetic sequencing, qPCR positives were subjected to cPCR, of which 12 positives were successfully amplified. The human adenovirus was identified with a nucleotide identity range of 98.48% to 99.53% compared with the reference genome from GenBank. The BMFS and SM flocculation were the most consistent viral concentration methods for HAdV and RVA, respectively. A statistical analysis of the positives showed that viral positivity differed by site (p < 0.001). SM and PEG may be the most appropriate options in resource-limited settings such as Zambia due to the lower costs associated with these concentration methods. The demonstration of HAdV and RVA detection in wastewater suggests the presence of the pathogens in the communities under study and the need to establish a routine wastewater surveillance system for the identification of pathogens. Full article

Introduction: Maintaining adequate nutritional status can be a challenge for patients with small bowel neuroendocrine tumours (NETs). Surgical resection could result in short bowel syndrome (SBS), whilst without surgical resection there is a considerable risk of ischemia or developing an inoperable malignant bowel obstruction (IMBO). SBS or IMBO are forms of intestinal failure (IF) which might require treatment with home parenteral nutrition (HPN). Limited data exist regarding the use of HPN in patients with small bowel neuroendocrine tumours, and it is not frequently considered as a possible treatment. Methods: A systematic review was performed regarding patients with small bowel NETs and IF to report on overall survival and HPN-related complications and create awareness for this treatment. Results: Five articles regarding patients with small bowel NETs or a subgroup of patients with NETs could be identified, mainly case series with major concerns regarding bias. The studies included 60 patients (range 1–41). The overall survival time varied between 0.5 and 154 months on HPN. However, 58% of patients were alive 1 year after commencing HPN. The reported catheter-related bloodstream infection rate was 0.64–2 per 1000 catheter days. Conclusion: This systematic review demonstrates the feasibility of the use of HPN in patients with NETs and IF in expert centres with a reasonable 1-year survival rate and low complication rate. Further research is necessary to compare patients with NETs and IF with and without HPN and the effect of HPN on their quality of life. Full article

Nature-based solutions (NBS) have been central to the European Union’s drive to address climate change, ecological degradation, and promote urban prosperity. Via an examination of the Horizon 2020-funded URBAN GreenUP project in Liverpool, this paper explores mainstreaming NBS in city planning. It uses evidence from pre- and post-intervention surveys with Liverpool residents and interviews with local business, environmental, government, and community sector experts to illustrate how a complex interplay of scale, location, focus, and visibility of NBS influences perceptions of the added value of NBS. This paper highlights the requirement that NBS interventions be bespoke and responsive to the overarching needs of residents and other stakeholders. Moreover, we underscore the importance of expert input into the design, location, and maintenance of NBS and call for these key drivers of successful delivery to be better integrated into work programs. This paper also notes that the type and size of NBS interventions impact perceptions of their value, with smaller projects being viewed as less socially and ecologically valuable compared to larger investments. We conclude that while small-scale NBS can support climatic, health, or ecological improvements in specific instances, strategic, larger-scale, and more visible investments are required to accrue substantive benefits and gain acceptance of NBS as a legitimate and effective planning tool. Full article

Youth-focused community and citizen science (CCS) is increasingly used to promote science learning and to increase the accessibility of the tools of scientific research among historically marginalized and underserved communities. CCS projects are frequently categorized according to their level of public participation and their distribution of power between professional scientists and participants from collaborative and co-created projects to projects where participants have limited roles within the science process. In this study, we examined how two different CCS models, a contributory design and a co-created design, influenced science self-efficacy and science interest among youth CCS participants. We administered surveys and conducted post-program interviews with youth participation in two different CCS projects in Alaska, the Winterberry Project and Fresh Eyes on Ice, each with a contributory and a co-created model. We found that youth participating in co-created CCS projects reflected more often on their science self-efficacy than did youth in contributory projects. The CCS program model did not influence youths’ science interest, which grew after participating in both contributory and co-created projects. Our findings suggest that when youth have more power and agency to make decisions in the science process, as in co-created projects, they have greater confidence in their abilities to conduct science. Further, participating in CCS projects excites and engages youth in science learning, regardless of the CCS program design. Full article

Rectal neuroendocrine neoplasms are increasing in incidence, in part due to increased endoscopic procedures being performed for bowel cancer screening. Whilst most of these lesions are low-grade well-differentiated neuroendocrine tumours, they can have a varied clinical behaviour. Frequently, these lesions are incorrectly characterised at endoscopy and, therefore, incompletely excised using standard polypectomy techniques. Furthermore, some cases are not fully staged prior to or post resection. In this article we discuss the endoscopic and surgical options available to improve the likelihood of achieving an R0 resection and the staging procedures that should be used in these NETs. We also review factors that may suggest a higher risk of nodal involvement or recurrence. This information may help determine whether endoscopic or surgical resection techniques should be considered. In cases of R1 resection we discuss the management options available and the long-term surveillance options and when these should be offered to patients. Full article

Since the sensorial profile is the cornerstone for the development of kombucha as a beverage with mass market appeal, advanced analytical tools are needed to gain a better understanding of the kinetics of aromatic compounds during the fermentation process to control the sensory profiles of the drink. The kinetics of volatile organic compounds (VOCs) was determined using stir bar sorptive extraction—gas chromatography—mass spectrometry, and odor-active compounds were considered to estimate consumer perception. A total of 87 VOCs were detected in kombucha during the fermentation stages. The synthesis of mainly phenethyl alcohol and isoamyl alcohol probably by Saccharomyces genus led to ester formation. Moreover, the terpene synthesis occurring at the beginning of fermentation (Δ-3-carene, α-phellandrene, γ-terpinene, m- and p-cymene) could be related to yeast activity as well. Principal component analysis identified classes that allowed the major variability explanation, which are carboxylic acids, alcohols, and terpenes. The aromatic analysis accounted for 17 aroma-active compounds. These changes in the evolution of VOCs led to flavor variations: from citrus-floral-sweet notes (geraniol and linalool domination), and fermentation brought intense citrus-herbal-lavender-bergamot notes (α-farnesene). Finally, sweet-floral-bready-honey notes dominated the kombucha flavor (2-phenylethanol). As this study allowed to estimate kombucha sensory profiles, an insight for the development of new drinks by controlling the fermentation process was suggested. Such a methodology should allow a better control and optimization of their sensory profile, which could in turn lead to greater consumer acceptance. Full article

Childhood obesity is considered a major public health problem. To help prevention and intervention programs targeting families with obese children, this paper is aimed at synthesizing multifactorial and transactional data resulting from studies and reviews assessing relational factors between the child and his or her parents and the child’s obesity risk, including the child’s and CG’s attachment quality, parental feeding practices, and family routines. It is also aimed at assessing the mediation of these links by specific self-regulatory capacities across different developmental periods (0–2, 2–8, and 8–18 years old). The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were applied in the review methodology. Ten papers were analyzed, including seven empirical studies and three reviews proposing etiological models of childhood obesity. The quality of empirical studies was assessed, and a synthetical model of the results was proposed. This literature review showed that the caregiver’s (CG) and the child’s attachment quality, along with controlling or permissive feeding practices, and few family routines are mostly mediated by appetite dysregulation and emotional regulation strategies with the development of child obesity. New research topics are proposed to understand other facets of childhood obesity, as well as how to better prevent and treat it. Full article

Cold Atmospheric Plasma (CAP) is an emerging technology with great potential for biomedical applications such as sterilizing equipment and antitumor strategies. CAP has also been shown to improve skin wound healing in vivo, but the biological mechanisms involved are not well known. Our study assessed a possible effect of a direct helium jet CAP treatment on keratinocytes, in both the immortalized N/TERT-1 human cell line and primary keratinocytes obtained from human skin samples. The cells were covered with 200 µL of phosphate buffered saline and exposed to the helium plasma jet for 10–120 s. In our experimental conditions, micromolar concentrations of hydrogen peroxide, nitrite and nitrate were produced. We showed that long-time CAP treatments (≥60 s) were cytotoxic, reduced keratinocyte migration, upregulated the expression of heat shock protein 27 (HSP27) and induced oxidative cell stress. In contrast, short-term CAP treatments (<60 s) were not cytotoxic, did not affect keratinocyte proliferation and differentiation, and did not induce any changes in mitochondria, but they did accelerate wound closure in vitro by improving keratinocyte migration. In conclusion, these results suggest that helium-based CAP treatments improve wound healing by stimulating keratinocyte migration. The study confirms that CAP could be a novel therapeutic method to treat recalcitrant wounds. Full article

Globally, migraine is a leading cause of disability with a huge impact on both the work and private life of affected persons. To overcome the societal migraine burden, better treatment options are needed. Increasing evidence suggests that ATP-sensitive potassium (K_ATP) channels are involved in migraine pathophysiology. These channels are essential both in blood glucose regulation and cardiovascular homeostasis. Experimental infusion of the K_ATP channel opener levcromakalim to healthy volunteers and migraine patients induced headache and migraine attacks in 82-100% of participants. Thus, this is the most potent trigger of headache and migraine identified to date. Levcromakalim likely induces migraine via dilation of cranial arteries. However, other neuronal mechanisms are also proposed. Here, basic K_ATP channel distribution, physiology, and pharmacology are reviewed followed by thorough review of clinical and preclinical research on K_ATP channel involvement in migraine. K_ATP channel opening and blocking have been studied in a range of preclinical migraine models and, within recent years, strong evidence on the importance of their opening in migraine has been provided from human studies. Despite major advances, translational difficulties exist regarding the possible anti-migraine efficacy of K_ATP channel blockage. These are due to significant species differences in the potency and specificity of pharmacological tools targeting the various K_ATP channel subtypes. Full article

We surveyed the insect fauna associated with Urophora cardui L. (Diptera: Tephritidae) galls on Canada thistle, Cirsium arvense L. (Asterales, Asteraceae), in parts of the northern Great Plains, U.S., by field-collecting galls and rearing or dissecting out the insects. We also examined the relationships between gall biomass and insect density and biomass. Urophora cardui were widespread, and the gall biomass was positively correlated with fly density and fly biomass. We recovered Isohydnocera tabida (LeConte) (Coleoptera: Cleridae) from galls in two counties, which represents a new host record and provides vital information on the little-known immatures of this predatory species. Pteromalus elevatus (Walker) (Hymenoptera: Pteromalidae) was the dominant parasitoid that emerged from the U. cardui galls. Individual galls typically only had one insect species, and occasionally both U. cardui and P. elevatus were present, but it was rare for other insects to be present in galls housing I. tabida. This study adds to the taxonomic literature of gall-inhabiting insect species and provides new information on the predators of U. cardui, specifically a little-known clerid beetle species. Full article

Cystic fibrosis (CF) newborn screening (NBS) was universally adopted in 2009 in the United States. Variations in NBS practices between states may impact the timing of diagnosis and intervention. Quantitative metrics can provide insight into NBS programs (NBSP), but the nuances cannot be elucidated without additional feedback from programs. This study was designed to determine facilitators and barriers to timely diagnosis and intervention following NBS for CF. The median age at the first CF event for infants with CF within each state was used to define early and late states (n = 15 per group); multiple CF centers were invited in states with more than two CF centers. Thirty states were eligible, and 61 NBSP and CF centers were invited to participate in structured interviews to determine facilitators and barriers. Once saturation of themes was reached, no other interviews were conducted. Forty-five interviews were conducted (n = 16 early CF center, n = 12 late CF center, n = 11 early NBSP, and n = 6 late NBSP). Most interviewees reported good communication between CF centers and NBSP. Communication between primary care providers (PCPs) and families was identified as a challenge, leading to delays in referral and subsequent diagnosis. The misperception of low clinical risk in infants from racial and ethnic minority groups was a barrier to early diagnostic evaluation for all groups. NBSP and CF centers have strong relationships. Early diagnosis may be facilitated through more engagement with PCPs. Quality improvement initiatives should focus on continuing strong partnerships between CF centers and NBS programs, improving education, communication strategies, and partnerships with PCPs, and improving CF NBS timeliness and accuracy. Full article

The treatment of acute myeloid leukemia (AML) remains a challenge especially among the elderly. The Bcl-2 inhibitor venetoclax recently showed significant survival benefits in AML patients when combined to low-dose cytarabine or azacitidine. Bcl-2 inhibition initiate mitochondrial apoptosis, but also respiration and cellular ATP production in AML. AMP-Activated Protein Kinase (AMPK) is a central energy sensor activated by increased AMP:ATP ratio to restore the cellular energy balance. Unexpectedly, we observed that venetoclax inhibited AMPK activity through caspase-dependent degradation of AMPK subunits in AML cells. On the other hand, genetic models of AMPK invalidation and re-expression suggested that AMPK participated to the early stages of apoptotic response through a negative regulation of multi-domain anti-apoptotic effectors such as Mcl-1 or Bcl-xL. Together our results suggested a new link between AMPK and Bcl-2-dependent mitochondrial apoptosis that participated to the anti-leukemic activity of venetoclax in AML. Full article

Objectives. We aimed to evaluate the effectiveness of a multifaceted procedure in improving pneumococcal and influenza vaccinations 6 months after an emergency department (ED) visit among patients aged 65 years and older. Methods. We conducted a cluster-randomized, controlled, parallel-group, open-label implementation trial in 18 EDs in France and Monaco. Participants were recruited from November 2015 to September 2016. EDs were randomly assigned with a 1:1 ratio to provide either a multifaceted procedure that combined structured information about pneumococcal and influenza vaccines and three text message reminders sent to patients every two weeks (intervention arm) or nonstructured information only (control arm). The outcomes were self-reported pneumococcal vaccination and influenza vaccination rates within 6 months of enrollment. Results. A total of 9 EDs were randomized to the intervention arm (n = 780 patients) and 9 to the control arm (n = 695 patients). The median age for all enrolled patients was 74 years (25–75th percentiles, 69 to 82): 50.1% were male, 34.9% had at least one underlying condition, and 30.7% were at risk for invasive pneumococcal infection. In the intention-to-treat analysis, the multifaceted intervention did not alter the pneumococcal vaccination rate (6.4% versus 4.6%, absolute difference: 1.8; 95% CI: [−0.9 to 4.4]; p = 0.19), whereas it improved the influenza vaccination rate (52.1% versus 40.0%, absolute difference: 12.1; 95% CI: [2.4 to 21.8]; p = 0.01). At 12 months, mortality did not differ between the intervention (9.7%) and control (11.2%) arms (p = 0.35). Conclusions. A multifaceted intervention based on text message reminders provides an opportunity to increase anti-influenza vaccination among elderly patients visiting the ED. Efforts are warranted to provide better information on pneumococcal diseases and the benefits of pneumococcal vaccines, especially in the elderly. Full article

Trillions of microorganisms, termed the “microbiota”, reside in the mammalian gastrointestinal tract, and collectively participate in regulating the host phenotype. It is now clear that the gut microbiota, metabolites, and intestinal immune function are correlated, and that alterations of the complex and dynamic host-microbiota interactions can have deep consequences for host health. However, the mechanisms by which the immune system regulates the microbiota and by which the microbiota shapes host immunity are still not fully understood. This article discusses the contribution of metabolites in the crosstalk between gut microbiota and immune cells. The identification of key metabolites having a causal effect on immune responses and of the mechanisms involved can contribute to a deeper insight into host-microorganism relationships. This will allow a better understanding of the correlation between dysbiosis, microbial-based dysmetabolism, and pathogenesis, thus creating opportunities to develop microbiota-based therapeutics to improve human health. In particular, we systematically review the role of soluble and membrane-bound microbial metabolites in modulating host immunity in the gut, and of immune cells-derived metabolites affecting the microbiota, while discussing evidence of the bidirectional impact of this crosstalk. Furthermore, we discuss the potential strategies to hear the sound of such metabolite-mediated crosstalk. Full article