Psychol Med. 2022 May 19:1-8. doi: 10.1017/S0033291722001362. Online ahead of print.

ABSTRACT

BACKGROUND: Previous research has suggested that statistical power is suboptimal in many biomedical disciplines, but it is unclear whether power is better in trials for particular interventions, disorders, or outcome types. We therefore performed a detailed examination of power in trials of psychotherapy, pharmacotherapy, and complementary and alternative medicine (CAM) for mood, anxiety, and psychotic disorders.

METHODS: We extracted data from the Cochrane Database of Systematic Reviews (Mental Health). We focused on continuous efficacy outcomes and estimated power to detect predetermined effect sizes (standardized mean difference [SMD] = 0.20-0.80, primary SMD = 0.40) and meta-analytic effect sizes (ESMA). We performed meta-regression to estimate the influence of including underpowered studies in meta-analyses.

RESULTS: We included 256 reviews with 10 686 meta-analyses and 47 384 studies. Statistical power for continuous efficacy outcomes was very low across intervention and disorder types (overall median [IQR] power for SMD = 0.40: 0.32 [0.19-0.54]; for ESMA: 0.23 [0.09-0.58]), only reaching conventionally acceptable levels (80%) for SMD = 0.80. Median power to detect the ESMA was higher in treatment-as-usual (TAU)/waitlist-controlled (0.49-0.63) or placebo-controlled (0.12-0.38) trials than in trials comparing active treatments (0.07-0.13). Adequately-powered studies produced smaller effect sizes than underpowered studies (B = -0.06, p ⩽ 0.001).

CONCLUSIONS: Power to detect both predetermined and meta-analytic effect sizes in psychiatric trials was low across all interventions and disorders examined. Consistent with the presence of reporting bias, underpowered studies produced larger effect sizes than adequately-powered studies. These results emphasize the need to increase sample sizes and to reduce reporting bias against studies reporting null results to improve the reliability of the published literature.

PMID:35588241 | DOI:10.1017/S0033291722001362

PLoS Genet. 2022 May 19;18(5):e1010135. doi: 10.1371/journal.pgen.1010135. eCollection 2022 May.

ABSTRACT

Physical and mental health are determined by an interplay between nature, for example genetics, and nurture, which encompasses experiences and exposures that can be short or long-lasting. The COVID-19 pandemic represents a unique situation in which whole communities were suddenly and simultaneously exposed to both the virus and the societal changes required to combat the virus. We studied 27,537 population-based biobank participants for whom we have genetic data and extensive longitudinal data collected via 19 questionnaires over 10 months, starting in March 2020. This allowed us to explore the interaction between genetics and the impact of the COVID-19 pandemic on individuals' wellbeing over time. We observe that genetics affected many aspects of wellbeing, but also that its impact on several phenotypes changed over time. Over the course of the pandemic, we observed that the genetic predisposition to life satisfaction had an increasing influence on perceived quality of life. We also estimated heritability and the proportion of variance explained by shared environment using variance components methods based on pedigree information and household composition. The results suggest that people's genetic constitution manifested more prominently over time, potentially due to social isolation driven by strict COVID-19 containment measures. Overall, our findings demonstrate that the relative contribution of genetic variation to complex phenotypes is dynamic rather than static.

PMID:35588108 | DOI:10.1371/journal.pgen.1010135

Adv Nutr. 2022 May 19:nmac058. doi: 10.1093/advances/nmac058. Online ahead of print.

ABSTRACT

The immune system is weakened by advancing age, often referred to as immunosenescence, increasing the vulnerability to, and frequently the severity of, infectious diseases in older people. This has become very apparent in the current coronavirus disease 2019 (COVID-19) pandemic for which older people are at higher risk of severe outcomes, even those who are fully vaccinated. Aging affects both the innate and adaptive immune systems and is characterized by an imbalanced inflammatory response. Increasing evidence shows that optimal status of nutrients such as vitamins C, D and E, selenium and zinc as well as the omega-3 fatty acids docosahexaenoic (DHA) and eicosapentaenoic acid (EPA) can help compensate for these age-related changes. While inadequate intakes of these nutrients are widespread in the general population, this is often more pronounced in older people. Maintaining adequate intakes is a challenge for them due to a range of factors such as physical, physiological and cognitive changes, altered absorption and the presence of non-communicable diseases. While nutritional requirements are ideally covered by a balanced diet, this can be difficult to achieve, particularly for older people. Fortified foods and nutritional complements are effective in achieving adequate micronutrient intakes and should be considered as a safe and cost-effective means for older people to improve their nutritional status and hence support their defense against infections. Complementing the diet with a combination of micronutrients, particularly those playing a key role in the immune system such as vitamins C, D and E, selenium and zinc as well as DHA and EPA is recommended for older people. Optimal nutrition to support the immune system in older people will remain essential, particularly in the face of the current COVID-19 pandemic and, thus, developing strategies to ensure adequate nutrition for the growing number of older adults will be an important and cost-effective investment in the future.

PMID:35587877 | DOI:10.1093/advances/nmac058

Acta Neuropsychiatr. 2022 May 19:1-36. doi: 10.1017/neu.2022.15. Online ahead of print.

ABSTRACT

INTRODUCTION: The multiplicity and complexity of the neuronal connections in the central nervous system make it difficult to disentangle circuits that play an essential role in the development or treatment of (neuro)psychiatric disorders. By choosing the evolutionary development of the forebrain as a starting point, a certain order in the connections can be created. The dorsal diencephalic connection (DDC) system can be applied for the development of biomarkers that can predict treatment response.

MATERIALS AND METHODS: After providing a brief introduction to the theory, we examined neuroanatomical publications on the connectivity of the DDC system. We then searched for neurochemical components that are specific for the habenula.

RESULTS AND DISCUSSION: The best strategy to find biomarkers which reflect the function of the habenular connection is to use genetic variants of receptors, transporters or enzymes specific to this complex. By activating these with probes and measuring the response in people with different functional genotypes, the usefulness of biomarkers can be assessed.

CONCLUSION: The most promising biomarkers in this respect are those linked to activation or inhibition of the nicotine receptor, dopamine D4 receptor, μ-opioid receptor and also those of the functioning of habenular glia cells (astrocytes and microglia).

PMID:35587050 | DOI:10.1017/neu.2022.15

Front Public Health. 2022 May 2;10:832840. doi: 10.3389/fpubh.2022.832840. eCollection 2022.

ABSTRACT

BACKGROUND: A one-stop shop for disaster response services provides a central location for information and advice in an accessible way. Yet little is known about its organization and outcomes. After the MH17 airplane crash, the one-stop shop concept was realized through a digital environment called the Information and Referral Center (IRC). The aim of this study was to evaluate the experiences of users and providers in regard to the IRC and to identify improvement points for future IRCs.

METHOD: Data was collected among affected ones as well as involved organizations, using interviews, focus groups, surveys and online user information. Existing evaluation and quality models were combined to design the study and analyze the data.

RESULTS: First, affected ones and a variety of organizations involved were positive about the merits of the IRC. Affected ones indicated they perceived the IRC as a reliable source of information and appreciated the referral possibilities. Second, the feature of the IRC to serve as a community where affected ones could meet, share experiences and support each other was hardly used according to participants. Lastly, tracking evolving psychosocial needs and problems through the IRC was hampered due to difficulty in accessing relevant data.

CONCLUSIONS: The IRC helped organizations to structure and align their services. Affected ones were positive about its reliability and accessibility. An IRC has to be embedded within the established care structures. Future research could indicate whether an IRC is useful in other event types and population contexts as well.

PMID:35586001 | PMC:PMC9108207 | DOI:10.3389/fpubh.2022.832840

Liver Int. 2022 May 18. doi: 10.1111/liv.15310. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: The gut microbiome-related metabolites betaine and trimethylamine N-oxide (TMAO) affect major health issues. In cirrhosis, betaine metabolism may be diminished due to impaired hepatic betaine homocysteine methyltransferase activity, whereas TMAO generation from trimethylamine may be altered due to impaired hepatic flavin monooxygenase expression. Here we determined plasma betaine and TMAO levels in patients with end-stage liver disease and assessed their relationships with liver disease severity.

METHODS: Plasma betaine and TMAO concentrations were measured by nuclear magnetic resonance spectroscopy in 129 cirrhotic patients (TransplantLines cohort study; NCT03272841) and compared with levels from 4,837 participants of the PREVEND cohort study. Disease severity was assessed by Child-Pugh-Turcotte (CPT) classification and Model for End-stage Liver Disease (MELD) score.

RESULTS: Plasma betaine was on average 60% higher (P<0.001), whereas TMAO was not significantly lower in cirrhotic patients vs. PREVEND population (P=0.44). After liver transplantation (n=13), betaine decreased (P=0.017; P=0.36 vs. PREVEND population), whereas TMAO levels tended to increase (P=0.085) to higher levels than in the PREVEND population (P=0.003). Betaine levels were positively associated with CPT stage and MELD score (both P<0.001). The association with MELD score remained in fully adjusted analysis (P<0.001). The association of TMAO with MELD score did not reach significance (P=0.11). Neither betaine, nor TMAO levels were associated with mortality on the waiting list for liver transplantation (adjusted P=0.78 and P=0.44, respectively).

CONCLUSION: Plasma betaine levels are elevated in cirrhotic patients in parallel with disease severity, and decrease after liver transplantation.

PMID:35585781 | DOI:10.1111/liv.15310

Curr Opin Psychiatry. 2022 May 1;35(3):177-185. doi: 10.1097/YCO.0000000000000791. Epub 2022 Mar 17.

ABSTRACT

PURPOSE OF REVIEW: The high mortality and prevalence of metabolic syndrome in patients with schizophrenia spectrum disorders (SSD) is maintained by poor diet. This narrative review summarizes recent literature to provide a reflection of current eating habits, dietary preferences, and nutritional status of SSD patients. Elucidating these factors provides new insights for potential lifestyle treatment strategies for SSD.

RECENT FINDINGS: Only 10.7% of the SSD patients had a healthy dietary pattern, against 23% of the general population. The dietic component of the Keeping the Body in Mind Xtend lifestyle program increased diet quality with 10% for young people with first-episode psychosis, compared to baseline, which was predominantly driven by increased vegetable variety and amounts.

SUMMARY: Recent findings render poor dietary habits as potential targets for treatment of SSD patients. Further studies into anti-inflammatory diets and associations with gut-brain biomarkers are warranted. When proven, structured and supervised diet interventions may help SSD patients escape from this entrapment, as only supplementing nutrients or providing dietary advice lacks the impact to significantly reduce the risk of chronic physical illnesses.

PMID:35585755 | DOI:10.1097/YCO.0000000000000791

BMC Health Serv Res. 2022 May 18;22(1):669. doi: 10.1186/s12913-022-08070-7.

ABSTRACT

OBJECTIVE: This systematic literature review aims to demonstrate how Artificial Intelligence (AI) is currently used in emergency departments (ED) and how it alters the work design of ED clinicians. AI is still new and unknown to many healthcare professionals in emergency care, leading to unfamiliarity with its capabilities.

METHOD: Various criteria were used to establish the suitability of the articles to answer the research question. This study was based on 34 selected peer-reviewed papers on the use of Artificial Intelligence (AI) in the Emergency Department (ED), published in the last five years. Drawing on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, all articles were scanned, read full-text, and analyzed afterward.

RESULTS: The majority of the AI applications consisted of AI-based tools to aid with clinical decisions and to relieve overcrowded EDs of their burden. AI support was mostly offered during triage, the moment that sets the patient trajectory. There is ample evidence that AI-based applications could improve the clinical decision-making process.

CONCLUSION: The use of AI in EDs is still in its nascent stages. Many studies focus on the question of whether AI has clinical utility, such as decision support, improving resource allocation, reducing diagnostic errors, and promoting proactivity. Some studies suggest that AI-based tools essentially have the ability to outperform human skills. However, it is evident from the literature that current technology does not have the aims or power to do so. Nevertheless, AI-based tools can impact clinician work design in the ED by providing support with clinical decisions, which could ultimately help alleviate a portion of the increasing clinical burden.

PMID:35585603 | DOI:10.1186/s12913-022-08070-7

Genome Med. 2022 May 18;14(1):51. doi: 10.1186/s13073-022-01052-8.

ABSTRACT

BACKGROUND: Protein truncating variants in ATM, BRCA1, BRCA2, CHEK2, and PALB2 are associated with increased breast cancer risk, but risks associated with missense variants in these genes are uncertain.

METHODS: We analyzed data on 59,639 breast cancer cases and 53,165 controls from studies participating in the Breast Cancer Association Consortium BRIDGES project. We sampled training (80%) and validation (20%) sets to analyze rare missense variants in ATM (1146 training variants), BRCA1 (644), BRCA2 (1425), CHEK2 (325), and PALB2 (472). We evaluated breast cancer risks according to five in silico prediction-of-deleteriousness algorithms, functional protein domain, and frequency, using logistic regression models and also mixture models in which a subset of variants was assumed to be risk-associated.

RESULTS: The most predictive in silico algorithms were Helix (BRCA1, BRCA2 and CHEK2) and CADD (ATM). Increased risks appeared restricted to functional protein domains for ATM (FAT and PIK domains) and BRCA1 (RING and BRCT domains). For ATM, BRCA1, and BRCA2, data were compatible with small subsets (approximately 7%, 2%, and 0.6%, respectively) of rare missense variants giving similar risk to those of protein truncating variants in the same gene. For CHEK2, data were more consistent with a large fraction (approximately 60%) of rare missense variants giving a lower risk (OR 1.75, 95% CI (1.47-2.08)) than CHEK2 protein truncating variants. There was little evidence for an association with risk for missense variants in PALB2. The best fitting models were well calibrated in the validation set.

CONCLUSIONS: These results will inform risk prediction models and the selection of candidate variants for functional assays and could contribute to the clinical reporting of gene panel testing for breast cancer susceptibility.

PMID:35585550 | DOI:10.1186/s13073-022-01052-8

Transl Psychiatry. 2022 May 18;12(1):207. doi: 10.1038/s41398-022-01973-3.

ABSTRACT

Sexual assault and rape are crimes that impact victims worldwide. Although the psychosocial and eco-evolutionary factors associated with this antisocial behavior have repeatedly been studied, the underlying neurobiological mechanisms are still largely unknown. Here, we established a novel paradigm to provoke and subsequently assess sexual aggression (SxA) in adult male Wistar rats: the sexual aggression test (SxAT). Briefly, male Wistar rats are sexually aroused by a receptive female, which is exchanged by a non-receptive female immediately after the first intromission. This protocol elicits forced mounting and aggressive behavior toward the non-receptive female to different degrees, which can be scored. In a series of experiments we have shown that SxA behavior is a relatively stable trait in rats and correlates positively with sexual motivation. Rats with innate abnormal anxiety and aggressive behavior also show abnormal SxA behavior. In addition, central infusion of oxytocin moderately inhibits aggressive behavior, but increases forced mounting. Finally, we identified the agranular insular cortex to be specifically activated by SxA, however, inhibition of this region did not significantly alter behavior in the SxAT. Altogether, the SxAT is a paradigm that can be readily implemented in behavioral laboratories as a valuable tool to find answers regarding the biological mechanisms underlying SxA in humans, as well as social decision-making in general.

PMID:35585046 | DOI:10.1038/s41398-022-01973-3

Arch Phys Med Rehabil. 2022 May 15:S0003-9993(22)00402-6. doi: 10.1016/j.apmr.2022.04.012. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine the effects of Exergaming on quality of life (QoL), motor, and clinical symptoms in Multiple Sclerosis. We compared the effects of exergaming (EXE), balance (BAL), cycling (CYC), proprioceptive neuromuscular facilitation (PNF), and a standard care wait-listed control group (CON) on clinical and motor symptoms and quality of life (QoL) in people with MS (PwMS) and determined the effects of subsequent maintenance programs for 2 years in a hospital setting.

DESIGN: A randomized clinical trial, using before-after test design.

SETTINGS: University Hospital Setting PARTICIPANTS: Of 82 multiple sclerosis outpatients, 70 were randomized, and 68 completed the study.

INTERVENTIONS: The initial high-intensity and -frequency interventions consisted of 25, 1-h sessions over 5 weeks. After the 5-wk-long initial intervention, the 2-year-long maintenance programs followed, consisting of 3 sessions per week, each for 1h.

MAIN OUTCOME MEASURES: The primary outcome: Multiple Sclerosis Impact Scale (MSIS-29).

SECONDARY OUTCOMES: Measures five aspects of health-related QoL (EQ-5D index), Beck Depression Inventory, six-minute walk test (6MWT), Berg Balance Scale (BBS), Tinetti Assessment Tool (TAT) and static balance (center of pressure, COP).

RESULTS: MSIS-29 improved most in EXE (11 points), BAL (6), and CYC (6, all p<0.05). QoL improved most in EXE (3 points) and CYC and BAL (2, all p<0.05). TAT and BBS improved significantly (p<0.05) but similarly (p>0.05) in EXE, BAL, and CYC. 6MWT improved most in EXE (57m), BAL (32m), and CYC (19m all p<0.001). Standing sway did not change. Maintenance programs further increased the initial exercise-induced gains, robustly in EXE.

CONCLUSION: 25 sessions of EXE, BAL, CYC, and PNF, in this order, improved clinical and motor symptoms and QoL and subsequent, 2-y-long thrice weekly maintenance programs further slowed symptom-worsening and improved QoL. EXE was the most and PNF was the least effective to improve clinical symptoms, motor function, and QoL in PwMS.

PMID:35584738 | DOI:10.1016/j.apmr.2022.04.012

J Clin Oncol. 2022 May 18:JCO2200400. doi: 10.1200/JCO.22.00400. Online ahead of print.

ABSTRACT

PURPOSE: Determining the estrogen receptor (ER) status is essential in metastatic breast cancer (MBC) management. Whole-body ER imaging with 16α-[¹⁸F]fluoro-17β-estradiol positron emission tomography ([¹⁸F]FES-PET) is increasingly used for this purpose. To establish the clinical validity of the [¹⁸F]FES-PET, we studied the diagnostic accuracy of qualitative and quantitative [¹⁸F]FES-PET assessment to predict ER expression by immunohistochemistry in a metastasis.

METHODS: In a prospective multicenter trial, 200 patients with newly diagnosed MBC underwent extensive workup including molecular imaging. For this subanalysis, ER expression in the biopsied metastasis was related to qualitative whole-body [¹⁸F]FES-PET evaluation and quantitative [¹⁸F]FES uptake in the corresponding metastasis. A review and meta-analysis regarding [¹⁸F]FES-PET diagnostic performance were performed.

RESULTS: Whole-body [¹⁸F]FES-PET assessment predicted ER expression in the biopsied metastasis with good accuracy: a sensitivity of 95% (95% CI, 89 to 97), a specificity of 80% (66 to 89), a positive predictive value (PPV) of 93% (87 to 96), and a negative predictive value (NPV) of 85% (72 to 92) in 181 of 200 evaluable patients. Quantitative [¹⁸F]FES uptake predicted ER immunohistochemistry in the corresponding metastasis with a sensitivity/specificity of 91%/69% and a PPV/NPV of 90%/71% in 156 of 200 evaluable patients. For bone metastases, PPV/NPV was 92%/81%. Meta-analysis with addition of our data has increased diagnostic performance and narrowed the 95% CIs compared with previous studies with a sensitivity/specificity of both 86% (81 to 90 and 73 to 93, respectively).

CONCLUSION: In this largest prospective series so far, we established the clinical validity of [¹⁸F]FES-PET to determine tumor ER status in MBC. In view of the high diagnostic accuracy of qualitatively assessed whole-body [¹⁸F]FES-PET, this noninvasive imaging modality can be considered a valid alternative to a biopsy of a metastasis to determine ER status in newly MBC (ClinicalTrials.gov identifier: NCT01957332).

PMID:35584346 | DOI:10.1200/JCO.22.00400

Am J Respir Crit Care Med. 2022 May 18. doi: 10.1164/rccm.202201-0214OC. Online ahead of print.

ABSTRACT

RATIONALE: Pulmonary hyperinflation in patients with Chronic Obstructive Pulmonary Disease (COPD) has been related to smaller cardiac chamber sizes and impaired cardiac function. Nowadays, bronchoscopic lung volume reduction (BLVR) with endobronchial valves is a treatment option to reduce pulmonary hyperinflation in patients with severe emphysema.

OBJECTIVES: We hypothesized that reduction of hyperinflation would improve cardiac preload in this patient group. In addition, we investigated whether the treatment would result in elevated pulmonary artery pressures due to pulmonary vascular bed reduction.

METHODS: We included patients with emphysema and severe hyperinflation (defined by a baseline residual volume >175% of predicted) who were eligible for BLVR with endobronchial valves. Cardiac magnetic resonance imaging was obtained one day prior to treatment and at eight week follow-up. Primary endpoint was cardiac preload, as measured by the right ventricle end-diastolic volume index (RVEDVI). As secondary endpoints, we measured indexed end-diastolic and end-systolic volumes of the right ventricle, left atrium, and left ventricle, pulmonary artery pressures, cardiac output, ejection fraction, and strain.

MEASUREMENTS AND MAIN RESULTS: Twenty-four patients were included. At eight week follow-up, RVEDVI was significantly improved (+7.9 ml/m2, SD 10.0, p=0.001). In addition to increased stroke volumes, we found significantly higher ejection fractions and strain measurements. Although cardiac output was significantly increased (+0.9L/min, SD 1.5, p=0.007), there were no changes in pulmonary artery pressures.

CONCLUSIONS: We found that reduction of hyperinflation using BLVR with endobronchial valves significantly improved cardiac preload, myocardial contractility, and cardiac output, without changes in pulmonary artery pressures. Clinical trial registered with ClinicalTrials.gov (NCT03474471).

PMID:35584341 | DOI:10.1164/rccm.202201-0214OC

Int J Geriatr Psychiatry. 2022 May 9;37(6). doi: 10.1002/gps.5736. Online ahead of print.

ABSTRACT

OBJECTIVES: Much is unknown about the combination of Medically Unexplained Symptoms (MUS) and alexithymia in later life, but it may culminate in a high disease burden for older patients. In the present study we assess the prevalence of alexithymia in older patients with either MUS or Medically Explained Symptoms (MES) and we explore physical, psychological and social correlates of alexithymia.

METHODS AND DESIGN: A case control study was performed. We recruited older persons (>60 years) with MUS (N = 118) or MES (N = 154) from the general public, general practitioner clinics and hospitals. Alexithymia was measured by the 20-item Toronto Alexithymia Scale, correlates were measured by various questionnaires.

RESULTS: Prevalence and severity of alexithymia were higher among older persons with MUS compared to MES. Alexithymia prevalence in the MUS subgroup was 23.7%. We found no association between alexithymia and increasing age. Alexithymia was associated with depressive symptoms, especially in the MUS population.

CONCLUSIONS: Alexithymia prevalence was lower than generally found in younger patients with somatoform disorder, but comparable to studies with similar diagnostic methods for MUS. Considering the high prevalence and presumed etiological impact of alexithymia in older patients with MUS, as well as its association with depression, this stresses the need to develop better understanding of the associations between alexithymia, MUS and depression in later life.

PMID:35584287 | DOI:10.1002/gps.5736

Int J Cancer. 2022 May 18. doi: 10.1002/ijc.34124. Online ahead of print.

ABSTRACT

The addition of hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin to interval cytoreductive surgery improves recurrence-free (RFS) and overall survival (OS) in patients with stage III ovarian cancer. Homologous recombination deficient (HRD) ovarian tumors are usually more platinum sensitive. Since hyperthermia impairs BRCA1/2 protein function, we hypothesized that HRD tumors respond best to treatment with HIPEC. We analyzed the effect of HIPEC in patients in the OVHIPEC trial, stratified by HRD status and BRCAm status. Clinical data and tissue samples were collected from patients included in the randomized, phase III OVHIPEC-1 trial. DNA copy number variation (CNV) profiles, HRD-related pathogenic mutations, and BRCA1 promotor hypermethylation were determined. CNV-profiles were categorized as HRD or non-HRD, based on a previously validated algorithm-based BRCA1-like classifier. Hazard ratios (HR) and corresponding 99% confidence intervals (CI) for the effect of RFS and OS of HIPEC in the BRCAm, the HRD/BRCAwt and the non-HRD group were estimated using Cox proportional hazard models. DNA was available from 200/245 (82%) patients. Seventeen (9%) tumors carried a pathogenic mutation in BRCA1 and 14 (7%) in BRCA2. Ninety-one (46%) tumors classified as BRCA1-like. The effect of HIPEC on RFS and OS was absent in BRCAm tumors (HR 1.25; 99%CI 0.48-3.29), and most present in HRD/BRCAwt (HR 0.44; 99%CI 0.21-0.91), and non-HRD/BRCAwt tumors (HR 0.82; 99%CI 0.48-1.42), interaction p-value: 0.024. Patients with HRD tumors without pathogenic BRCA1/2 mutation appear to benefit most from treatment with HIPEC, while benefit in patients with BRCA1/2 pathogenic mutations and patients without HRD seems less evident.

PMID:35583992 | DOI:10.1002/ijc.34124

Ann Surg Oncol. 2022 May 18. doi: 10.1245/s10434-022-11837-1. Online ahead of print.

ABSTRACT

BACKGROUND: Surgery with radical intent is the only potentially curative option for entero-pancreatic neuroendocrine tumors (EP-NETs) but many patients develop recurrence even after many years. The subset of patients at high risk of disease recurrence has not been clearly defined to date.

OBJECTIVE: The aim of this retrospective study was to define, in a series of completely resected EP-NETs, the recurrence-free survival (RFS) rate and a risk score for disease recurrence.

PATIENTS AND METHODS: This was a multicenter retrospective analysis of sporadic pancreatic NETs (PanNETs) or small intestine NETs (SiNETs) [G1/G2] that underwent R0/R1 surgery (years 2000-2016) with at least a 24-month follow-up. Survival analysis was performed using the Kaplan-Meier method and risk factor analysis was performed using the Cox regression model.

RESULTS: Overall, 441 patients (224 PanNETs and 217 SiNETs) were included, with a median Ki67 of 2% in tumor tissue and 8.2% stage IV disease. Median RFS was 101 months (5-year rate 67.9%). The derived prognostic score defined by multivariable analysis included prognostic parameters, such as TNM stage, lymph node ratio, margin status, and grading. The score distinguished three risk categories with a significantly different RFS (p < 0.01).

CONCLUSIONS: Approximately 30% of patients with EP-NETs recurred within 5 years after radical surgery. Risk factors for recurrence were disease stage, lymph node ratio, margin status, and grading. The definition of risk categories may help in selecting patients who might benefit from adjuvant treatments and more intensive follow-up programs.

PMID:35583694 | DOI:10.1245/s10434-022-11837-1

Stem Cells Dev. 2022 May 18. doi: 10.1089/scd.2022.0003. Online ahead of print.

ABSTRACT

Insufficient vascularization is a recurring cause of impaired pedicled skin flap healing. The administration of adipose tissue-derived stromal cells' (ASC) secretome is a novel approach to augment vascularization. Yet, the secretome comprised soluble factors that require a sustained release vehicle to increase residence time. We hypothesized that administration of a hydrogel derived from decellularized extracellular matrix (ECM) of porcine skin with bound trophic factors from ASCs, enhances skin flap viability and wound repair in a rat model. Porcine skin was decellularized and pepsin-digested to form a hydrogel at 37°C. Conditioned medium (CMe) of human ASC was collected, concentrated twentyfold and mixed with the hydrogel. Sixty Wistar rats were included. A dorsal skin flap (caudal based) of 3 x 10 cm was elevated for topical application of: DMEM medium (group I), a pre-hydrogel with or without ASC CMe (group II and III) or ASC CMe (group IV). After 7, 14 and 28 days, perfusion was measured and skin flaps were harvested for wound healing assessment and immunohistochemical analysis. Decellularized skin ECM hydrogel contained negligible amounts of DNA (11.6 ± 0.6 ng/mg), was noncytotoxic and well-tolerated by rats. Irrespective of ASC secretome, ECM hydrogel application resulted macroscopically and microscopically in similar dermal wound healing in terms of proliferation, immune response and matrix remodeling as the control group. However, ASC CMe alone increased vessel density after seven days. Concluding, porcine skin derived ECM hydrogels loaded with ASC secretome are non-cytotoxic but demand optimization to significantly augment wound healing of skin flaps.

PMID:35583223 | DOI:10.1089/scd.2022.0003

Endocr Connect. 2022 May 1:EC-22-0021. doi: 10.1530/EC-22-0021. Online ahead of print.

ABSTRACT

BACKGROUND: Potential influences of the parathyroidectomy (PTx) on quality of life (QoL) in multiple endocrine neoplasia type 1-related primary hyperparathyroidism (HPT/MEN1) are unknown.

METHOD: Short Form 36 Health Survey Questionnaire was prospectively applied in 30 HPT/MEN1 patients submitted to PTx (20, subtotal; 10, total with autograft), before, 6 and 12 months (mo.) after surgery. Parameters analyzed included QoL, age, HPT-related symptoms, general pain, comorbidities, biochemical/hormonal response, PTx type and parathyroid volume.

RESULTS: Asymptomatic patients were younger (30 vs 38 years; p=0.04) and presented higher QoL scores (physical component score, PCS, 92.5 vs 61.2 p=0.0051; mental component score, MCS, 82.0 vs 56.0, p=0.04) than symptomatic ones. In both groups, QoL remained stable one year after PTx, independently of number of comorbidities. Preoperative general pain was negatively correlated with PCS (r =-0.60, p=0.0004) and MCS (r=-0.57, p=0.0009). Also, moderate/intense pain was progressively (6/12mo.) more frequent in cases developing hypoparathyroidism. The PTx type and hypoparathyroidism did not affect the QoL at 12mo. although remnant parathyroid tissue volume did have a positive correlation (p=0.0490; r=0.3625) to PCS 12mo. after surgery. Patients with 1-2 comorbidities had as pre-PTx PCS (p=0.0015) as 12mo. post-PTx PCS (p=0.0031) and MCS (p=0.0365) better than patients with 3-4 comorbidities.

CONCLUSION: A variable QoL profile was underscored in HPT/MEN1 reflecting multiple factors associated to this complex disorder as comorbidities, advanced age at PTx and presence of preoperative symptoms or of general pain perception. Our data encourage the early indication of PTx in HPT/MEN1 by providing known metabolic benefits to target-organs and avoiding potential negative impact on QoL.

PMID:35583183 | DOI:10.1530/EC-22-0021

Br J Surg. 2022 May 18:znac117. doi: 10.1093/bjs/znac117. Online ahead of print.

NO ABSTRACT

PMID:35583155 | DOI:10.1093/bjs/znac117

Eur J Oper Res. 2022 May 13. doi: 10.1016/j.ejor.2022.05.009. Online ahead of print.

ABSTRACT

The ongoing COVID-19 pandemic has led public health authorities to face the unprecedented challenge of planning a global vaccination campaign, which for most protocols entails the administration of two doses, separated by a bounded but flexible time interval. The partial immunity already offered by the first dose and the high levels of uncertainty in the vaccine supplies have been characteristic of most of the vaccines used worldwide and made the planning of such a vaccination campaign extremely complex. Motivated by this compelling challenge, we propose a stochastic optimization framework for optimally scheduling a two-dose vaccination campaign in the presence of uncertain supplies, taking into account constraints on the time that should elapse between the two doses and on the capacity of the healthcare system. The proposed framework seeks to maximize the vaccination coverage, considering the different levels of immunization obtained with partial (one dose only) and complete vaccination (two doses). We cast the optimization problem as a convex second-order cone program, which can be efficiently solved through numerical techniques. We demonstrate the potential of our framework on a case study calibrated on the COVID-19 vaccination campaign in Italy. The proposed method shows good performance when unrolled in a sliding-horizon fashion, thereby offering a powerful tool to help public health authorities calibrate the vaccination campaign, pursuing a trade off between efficacy and the risk due to shortages in supply.

PMID:35582705 | PMC:PMC9098718 | DOI:10.1016/j.ejor.2022.05.009

Curr Psychol. 2022 May 12:1-13. doi: 10.1007/s12144-022-03196-7. Online ahead of print.

ABSTRACT

Lockdown measures during the COVID-19 pandemic resulted in drastic disruptions of university students' everyday life and study mode, such as marked reductions in face-to-face teaching activities. Previous research on student mental health during the pandemic found that prolonged campus relocation had negative effects on students' mental well-being. However, these studies focussed on the initial lockdown period, or periods of active lockdown measures. This longitudinal study collected 456 observations of 23 undergraduate students in the Netherlands using ecological momentary assessment data on mental health related items (anxiety, stress, social context) during the first two weeks of on-campus teaching after prolonged lockdown measures. Using multi-level dynamic network modelling, we analysed the temporal and contemporaneous interplay of students' mental health factors following the return to campus in September 2021. On average, students reported low to medium scores on stress and anxiety both before and after the assessment period. Results of network analyses showed that students experienced social unease in relation to accumulating difficulties at university and vice versa. Furthermore, there were clusters of different states of social unease next to clusters of stress, anger, loss of control, and feeling upset. Lastly, we found beneficial effects of self-efficacy on experiencing social comfort in university. We discuss implications and concrete examples of interventions in universities, such as the promotion of self-efficacy, providing guidance in structuring study load, as well as help with stress management.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12144-022-03196-7.

PMID:35582434 | PMC:PMC9098144 | DOI:10.1007/s12144-022-03196-7

Macromol Rapid Commun. 2022 May 17:e2200045. doi: 10.1002/marc.202200045. Online ahead of print.

ABSTRACT

A biorenewable polymer was synthesized via a green process using the RAFT principle for the first time in supercritical CO2 at 300 bar and 80°C. α-Methylene-γ-butyrolactone polymers of various chain lengths and molecular weights were obtained. The molecular weights varied from 10000 up to 20000 with low polydispersity indexes (PDI <1.5). Furthermore, the monomer conversion in supercritical CO2 was substantially higher, respectively 85⁺ % for ScCO2 compared to around 65% for polymerizations conducted in dimethyl formamide (DMF) solvent. Chain extensions were carried out to confirm the livingness of the formed polymers in ScCO2. This opens up future possibilities of the formation of different polymer architectures in ScCO2. The polymers synthesized in ScCO2 have glass transition temperature (Tg) values ranging from 155°C up to 190°C. However, the presence of residual monomer encapsulated inside the formed polymer matrix affected the glass transition of the polymer which was lowered by increasing monomer concentrations. Hence, additional research is required to eliminate the remaining monomer concentration in the polymer matrix in order to arrive at the optimal Tg. This article is protected by copyright. All rights reserved.

PMID:35581933 | DOI:10.1002/marc.202200045

Transplantation. 2022 May 18. doi: 10.1097/TP.0000000000004175. Online ahead of print.

ABSTRACT

BACKGROUND: Apoptosis contributes to the severity of ischemia-reperfusion injury (IRI), limiting the use of extended criteria donors in liver transplantation (LT). Machine perfusion has been proposed as a platform to administer specific therapies to improve graft function. Alternatively, the inhibition of genes associated with apoptosis during machine perfusion could alleviate IRI post-LT. The aim of the study was to investigate whether inhibition of an apoptosis-associated gene (FAS) using a small interfering RNA (siRNA) approach could alleviate IRI in a rat LT model.

METHODS: In 2 different experimental protocols, FASsiRNA (500 µg) was administered to rat donors 2 h before organ procurement, followed by 22 h of static cold storage, (SCS) or was added to the perfusate during 1 h of ex situ hypothermic oxygenated perfusion (HOPE) to livers previously preserved for 4 h in SCS.

RESULTS: Transaminase levels were significantly lower in the SCS-FASsiRNA group at 24 h post-LT. Proinflammatory cytokines (interleukin-2, C-X-C motif chemokine 10, tumor necrosis factor alpha, and interferon gamma) were significantly decreased in the SCS-FASsiRNA group, whereas the interleukin-10 anti-inflammatory cytokine was significantly increased in the HOPE-FASsiRNA group. Liver absorption of FASsiRNA after HOPE session was demonstrated by confocal microscopy; however, no statistically significant differences on the apoptotic index, necrosis levels, and FAS protein transcription between treated and untreated groups were observed.

CONCLUSIONS: FAS inhibition through siRNA therapy decreases the severity of IRI after LT in a SCS protocol; however the association of siRNA therapy with a HOPE perfusion model is very challenging. Future studies using better designed siRNA compounds and appropriate doses are required to prove the siRNA therapy effectiveness during liver HOPE liver perfusion.

PMID:35581683 | DOI:10.1097/TP.0000000000004175

BMC Prim Care. 2022 May 17;23(1):118. doi: 10.1186/s12875-022-01729-4.

ABSTRACT

BACKGROUND: Physical inactivity has contributed to the current prevalence of many age-related diseases, including type 2 diabetes and cardiovascular disease. Peer coach physical activity intervention are effective in increasing long term physical activity in community dwelling older adults. Linking peer coach physical activity interventions to formal care could therefore be a promising novel method to improve health in inactive older adults to a successful long-term physical activity intervention.

METHODS: We evaluated the effects of linking a peer coach physical activity intervention in Leiden, The Netherlands to primary care through an exercise referral scheme from July 2018 to April 2020. Primary care practices in the neighborhoods of three existing peer coach physical activity groups were invited to refer patients to the exercise groups. Referrals were registered at the primary care practice and participation in the peer coach groups was registered by the peer coaches of the exercise groups.

RESULTS: During the study, a total of 106 patients were referred to the peer coach groups. 5.7% of patients participated at the peer coach groups and 66.7% remained participating during the 1 year follow up. The number needed to refer for 1 long term participant was 26.5. The mean frequency of participation of the referred participants was 1.2 times a week.

CONCLUSION: Linking a peer coach physical activity intervention for older adults to a primary care referral scheme reached only a small fraction of the estimated target population. However, of the people that came to the peer coach intervention a large portion continued to participate during the entire study period. The number needed to refer to engage one older person in long term physical activity was similar to other referral schemes for lifestyle interventions. The potential benefits could be regarded proportional to the small effort needed to refer.

PMID:35581538 | PMC:PMC9115932 | DOI:10.1186/s12875-022-01729-4

Mater Sci Eng C Mater Biol Appl. 2022 Feb 8:112693. doi: 10.1016/j.msec.2022.112693. Online ahead of print.

ABSTRACT

One of the most common magnesium (Mg) applications in the biomedical field is in cardiovascular stents. Although Mg is an essential element for homeostasis, Mg is highly reactive, and locally high Mg concentrations can have toxic effects on the surrounding tissue. One strategy to circumvent the Mg toxicity is using coatings or surface modifications that prevent the leaching of excessive Mg ions. In the current study, commercially pure magnesium (c.p Mg) was modified through plasma electrolytic oxidation (PEO) to produce a protective coating primarily composed of Mg oxide (MgO) and Mg hydroxide (Mg(OH)₂), which limits leaching of free Mg ions from the base material. As we intend to use this material to produce vascular stents, a biological evaluation of its performance is warranted. Primary human umbilical vein endothelial cells (HUVECs) and smooth muscle cells (SMCs) were the study object. The leaching of free Mg ions from the oxidized materials was investigated, as was its effect on local pH changes. We also investigated the influence of corrosion products, the effects of elevated free Mg concentrations and pH on the cellular behavior on the integrity of monolayers of HUVECs was studied in a static and dynamic model. Results showed that the harmful effect of Mg on cells due to changes in pH and a high concentration of Mg ions could decrease with the influence of flow diffusing corrosion products such as MgO, Mg(OH)₂, and H₂ among the system. Independently, Mg concentration and pH affected the cell activity of SMCs and HUVECs. Finally, to investigate the influence of leachables on vasomotor function, we exposed porcine aortic rings to PEO-modified Mg stents and assessed endothelial-dependent relaxation. Pure Mg reduced vasorelaxation from 100% in control samples to 30%. Oppositely, PEO-modified Mg did not affect the vasomotor function. Overall, we conclude from this study that the use of PEO coatings reduces the degradation rate of the material reducing the Mg release resulting in better cell viability and vessel function compared to the bare material.

PMID:35581088 | DOI:10.1016/j.msec.2022.112693

Gastroenterology. 2022 May 14:S0016-5085(22)00504-2. doi: 10.1053/j.gastro.2022.05.015. Online ahead of print.

ABSTRACT

BACKGROUND & AIMS: Previous randomized trials, including the TENSION trial, demonstrated that the endoscopic step-up approach might be preferred over the surgical step-up approach in patients with infected necrotizing pancreatitis based on favorable short-term outcomes. We compared long-term clinical outcomes of both step-up approaches after a period of at least 5 years.

METHODS: In this long-term follow-up study, we re-evaluated all clinical data on 83 patients (of the originally 98 included patients) from the TENSION trial who were still alive after the initial 6-months follow-up. The primary endpoint, similar to the TENSION trial, was a composite of death and major complications. Secondary endpoints included individual major complications, pancreaticocutaneous fistula, re-interventions, pancreatic insufficiency, and quality of life.

RESULTS: After a mean follow-up period of 7 years, the primary endpoint occurred in 27 patients (53%) in the endoscopy and in 27 patients (57%) in the surgery group (risk ratio [RR] 0.93, 95% confidence interval [CI] 0.65 to 1.32, P=0.688). Fewer pancreaticocutaneous fistulas were identified in the endoscopy group (8% vs. 34%; RR 0.23, 95% CI 0.08 to 0.83). After the initial 6-months follow-up, the endoscopy group needed fewer re-interventions than the surgery group (7% vs. 24%; RR 0.29, 95% CI 0.09 to 0.99). Pancreatic insufficiency and quality of life did not differ between groups.

CONCLUSIONS: At long-term follow-up, the endoscopic step-up approach was not superior to the surgical step-up approach in reducing death or major complications in patients with infected necrotizing pancreatitis. However, patients assigned to the endoscopic approach developed overall fewer pancreaticocutaneous fistulas and needed fewer re-interventions after the initial 6-months follow-up. Netherlands Trial Register no: NL8571.

PMID:35580661 | DOI:10.1053/j.gastro.2022.05.015

Am J Clin Nutr. 2022 May 17:nqac137. doi: 10.1093/ajcn/nqac137. Online ahead of print.

ABSTRACT

BACKGROUND: Potassium intake has been shown to be inversely associated with blood pressure and premature mortality. Previous studies suggested that the association between potassium intake and blood pressure is modified by obesity, but whether obesity similarly influences the association between potassium intake and mortality is unclear.

OBJECTIVES: To investigate whether potassium intake, reflected by 24-hour urinary excretion, is associated with all-cause mortality, and to explore potential effect modification by obesity.

METHODS: We performed a prospective cohort study in community-dwelling individuals. The association between urinary potassium excretion and all-cause mortality was investigated by multivariable Cox regression. We performed multiplicative interaction analysis and subgroup analyses according to BMI and waist circumference.

RESULTS: In 8,533 individuals (50% male) mean age was 50 ± 13 years, mean urinary potassium excretion was 71±21 mmol/24 hrs, median BMI was 25.6 (IQR 23.1-28.4) kg/m2 and mean waist circumference was 89±13 cm. During follow-up of 18.4 [IQR 13.5-18.8] years, 1,663 participants died. Low urinary potassium excretion (1st vs. 3rd sex-specific quintile) was associated with an increased mortality risk (fully adjusted HR 1.38 [95% CI 1.18, 1.61], P < 0.001, irrespective of body dimensions (Range of HR for all body dimensions 1.36 to 1.70, all P < 0.05). High urinary potassium excretion (5th vs. 3rd quintile) was associated with increased mortality risk in participants with obesity (BMI ≥30 kg/m2; HR 1.52 [1.00, 2.30]), but not in participants without obesity (BMI <25 kg/m2; HR 0.89 [0.62, 1.26]) (P-interaction = 0.001).

CONCLUSIONS: Low potassium intake was associated with increased mortality risk in community-dwelling individuals. In individuals with obesity, high potassium intake was also associated with increased mortality risk.

PMID:35580599 | DOI:10.1093/ajcn/nqac137

Curr Opin Psychiatry. 2022 May 1;35(3):137-139. doi: 10.1097/YCO.0000000000000781.

NO ABSTRACT

PMID:35579868 | DOI:10.1097/YCO.0000000000000781

Am J Respir Crit Care Med. 2022 May 17. doi: 10.1164/rccm.202204-0669ED. Online ahead of print.

NO ABSTRACT

PMID:35579662 | DOI:10.1164/rccm.202204-0669ED

Cancer. 2022 May 17. doi: 10.1002/cncr.34265. Online ahead of print.

ABSTRACT

BACKGROUND: Clinical pathways are care plans established to describe essential steps in the care of patients with a specific clinical problem. They translate (inter)national guidelines into local applicable protocols and clinical practice. The purpose of this article is to establish a multidisciplinary integrated care pathway for specialists and allied health care professionals in caring for individuals with von Hippel-Lindau (VHL) disease.

METHODS: Using a modified Delphi consensus-making process, a multidisciplinary panel from 5 Dutch University Medical Centers produced an integrated care pathway relating to the provision of care for patients with VHL by medical specialists, specialized nurses, and associated health care professionals. Patient representatives cocreated the pathway and contributed quality criteria from the patients' perspective.

RESULTS: The panel agreed on recommendations for the optimal quality of care for individuals with a VHL gene mutation. These items were the starting point for the development of a patient care pathway. With international medical guidelines addressing the different VHL-related disorders, this article presents a patient care pathway as a flowchart that can be incorporated into VHL expertise clinics or nonacademic treatment clinics.

CONCLUSIONS: Medical specialists (internists, urologists, neurosurgeons, ophthalmologists, geneticists, medical oncologists, neurologists, gastroenterologists, pediatricians, and ear-nose-throat specialists) together with specialized nurses play a vital role alongside health care professionals in providing care to people affected by VHL and their families. This article presents a set of consensus recommendations, supported by organ-specific guidelines, for the roles of these practitioners in order to provide optimal VHL care. This care pathway can form the basis for the development of comprehensive, integrated pathways for multiple neoplasia syndromes.

PMID:35579632 | DOI:10.1002/cncr.34265

Genet Med. 2022 May 17:S1098-3600(22)00727-4. doi: 10.1016/j.gim.2022.04.010. Online ahead of print.

ABSTRACT

PURPOSE: Genome-wide sequencing is increasingly being performed during pregnancy to identify the genetic cause of congenital anomalies. The interpretation of prenatally identified variants can be challenging and is hampered by our often limited knowledge of prenatal phenotypes. To better delineate the prenatal phenotype of Coffin-Siris syndrome (CSS), we collected clinical data from patients with a prenatal phenotype and a pathogenic variant in one of the CSS-associated genes.

METHODS: Clinical data was collected through an extensive web-based survey.

RESULTS: We included 44 patients with a variant in a CSS-associated gene and a prenatal phenotype; 9 of these patients have been reported before. Prenatal anomalies that were frequently observed in our cohort include hydrocephalus, agenesis of the corpus callosum, hypoplastic left heart syndrome, persistent left vena cava, diaphragmatic hernia, renal agenesis, and intrauterine growth restriction. Anal anomalies were frequently identified after birth in patients with ARID1A variants (6/14, 43%). Interestingly, pathogenic ARID1A variants were much more frequently identified in the current prenatal cohort (16/44, 36%) than in postnatal CSS cohorts (5%-9%).

CONCLUSION: Our data shed new light on the prenatal phenotype of patients with pathogenic variants in CSS genes.

PMID:35579625 | DOI:10.1016/j.gim.2022.04.010

Clin Exp Rheumatol. 2022 Apr 29. doi: 10.55563/clinexprheumatol/75tlgf. Online ahead of print.

ABSTRACT

OBJECTIVES: We aimed to determine the presence, amount and origin of microchimerism in peripheral blood of pregnant and non-pregnant parous women with systemic lupus erythematosus (SLE) as compared to control subjects.

METHODS: We performed a comparative study in which peripheral blood was drawn from eleven female non-pregnant SLE-patients and 22 control subjects, and from six pregnant SLE-patients and eleven control subjects during gestation and up to six months postpartum. Quantitative PCR for insertion-deletion polymorphisms and null alleles was used to detect microchimerism in peripheral blood mononuclear cells and granulocytes.

RESULTS: Microchimerism was detected more often in non-pregnant SLE-patients than control subjects (54.4% vs. 13.6%, respectively; p=0.03). When present, the median total number of foetal chimeric cells was 5 gEq/106 in patients and 2.5gEq/106 in control subjects (p=0.048). Microchimerism was mostly foetal in origin; maternal microchimerism was detected in one patient and one control subject. In control subjects, microchimerism was always derived from only one source whereas in 50% of patients it originated from multiple sources. The pregnant patients had a significantly higher median number of foetal chimeric cells in the granulocyte fraction just after delivery than control subjects (7.5 gEq/106 vs. 0 gEq/106, respectively; p=0.02).

CONCLUSIONS: Just after delivery, SLE-patients had more microchimerism than control subjects. Three months post-partum, microchimerism was no longer detectable, only to reappear many years after the last pregnancy, more often and at higher levels in SLE-patients than in control subjects. This suggests that these chimeric cells may originate from non-circulating foetal chimeric stem cells.

PMID:35579081 | DOI:10.55563/clinexprheumatol/75tlgf

Dev Med Child Neurol. 2022 May 16. doi: 10.1111/dmcn.15260. Online ahead of print.

ABSTRACT

AIM: To identify subtypes in a large group of children clinically diagnosed with developmental coordination disorder (DCD) based on their pattern of motor, cognitive, and visual-motor abilities.

METHOD: Standardized scores for verbal IQ, total IQ, Movement Assessment Battery for Children, Second Edition (MABC-2) balance, MABC-2 manual dexterity, MABC-2 ball skills, and Beery-Buktenica Developmental Tests of Visual-Motor Integration (Beery-VMI), Motor Coordination (Beery-MC), and Visual Perception (Beery-VP) were used. The NbClust complete procedure was used to best partition the data on 98 children (84 males, 14 females, mean [SD] age: 8 years [2 years 1 month]) into clusters. Deviation contrasts, multivariate analysis of variance, and post hoc comparisons were used to characterize the clusters.

RESULTS: Four clusters were revealed: two clusters with a broad motor skill problem, one with relatively preserved visual-motor integration and Beery-MC skills, and a second with abnormal ball skills, balance, and Beery-MC skills. A third cluster with more specific gross-motor problems, and a fourth with relatively preserved ball skills but low Beery-MC and performance IQ, were identified. Balance scores were 'at risk' or 'abnormal' in all four clusters.

INTERPRETATION: DCD is a heterogeneous condition. However, subtypes can be discriminated on the basis of more severe difficulties in fine-motor performance, gross-motor performance, or both. There was evidence for generalized motor impairments in around half of all children. Importantly, at least borderline level reduced balance was evident in each subtype.

PMID:35578393 | DOI:10.1111/dmcn.15260

Trials. 2022 May 16;23(1):405. doi: 10.1186/s13063-022-06367-w.

ABSTRACT

BACKGROUND: Although life-saving in selected patients, ECMO treatment still has high mortality which for a large part is due to treatment-related complications. A feared complication is ischemic stroke for which heparin is routinely administered for which the dosage is usually guided by activated partial thromboplastin time (aPTT). However, there is no relation between aPTT and the rare occurrence of ischemic stroke (1.2%), but there is a relation with the much more frequent occurrence of bleeding complications (55%) and blood transfusion. Both are strongly related to outcome.

METHODS: We will conduct a three-arm non-inferiority randomized controlled trial, in adult patients treated with ECMO. Participants will be randomized between heparin administration with a target of 2-2.5 times baseline aPTT, 1.5-2 times baseline aPTT, or low molecular weight heparin guided by weight and renal function. Apart from anticoagulation targets, treatment will be according to standard care. The primary outcome parameter is a combined endpoint consisting of major bleeding including hemorrhagic stroke, severe thromboembolic complications including ischemic stroke, and mortality at 6 months.

DISCUSSION: We hypothesize that with lower anticoagulation targets or anticoagulation with LMWH during ECMO therapy, patients will have fewer hemorrhagic complications without an increase in thromboembolic complication or a negative effect on their outcome. If our hypothesis is confirmed, this study could lead to a change in anticoagulation protocols and a better outcome for patients treated with ECMO.

TRIAL REGISTRATION: ClinicalTrials.gov NCT04536272 . Registered on 2 September 2020. Netherlands Trial Register NL7969.

PMID:35578271 | PMC:PMC9108348 | DOI:10.1186/s13063-022-06367-w

Eur J Hum Genet. 2022 May 16. doi: 10.1038/s41431-022-01113-x. Online ahead of print.

ABSTRACT

In 2016, guidelines for diagnostic Next Generation Sequencing (NGS) have been published by EuroGentest in order to assist laboratories in the implementation and accreditation of NGS in a diagnostic setting. These guidelines mainly focused on Whole Exome Sequencing (WES) and targeted (gene panels) sequencing detecting small germline variants (Single Nucleotide Variants (SNVs) and insertions/deletions (indels)). Since then, Whole Genome Sequencing (WGS) has been increasingly introduced in the diagnosis of rare diseases as WGS allows the simultaneous detection of SNVs, Structural Variants (SVs) and other types of variants such as repeat expansions. The use of WGS in diagnostics warrants the re-evaluation and update of previously published guidelines. This work was jointly initiated by EuroGentest and the Horizon2020 project Solve-RD. Statements from the 2016 guidelines have been reviewed in the context of WGS and updated where necessary. The aim of these recommendations is primarily to list the points to consider for clinical (laboratory) geneticists, bioinformaticians, and (non-)geneticists, to provide technical advice, aid clinical decision-making and the reporting of the results.

PMID:35577938 | DOI:10.1038/s41431-022-01113-x

Environ Int. 2022 May 10;164:107285. doi: 10.1016/j.envint.2022.107285. Online ahead of print.

ABSTRACT

BACKGROUND: Air pollution has been associated with carotid intima-media thickness test (CIMT), a marker of subclinical atherosclerosis. To our knowledge, this is the first study to report an association between ambient air pollution and CIMT in a younger adolescent population.

OBJECTIVE: To investigate the associations beyond standard mean regression by using quantile regression to explore if associations occur at different percentiles of the CIMT distribution.

METHODS: We measured CIMT cross-sectionally at the age of 16 years in 363 adolescents participating in the Dutch PIAMA birth cohort. We fit separate quantile regressions to examine whether the associations of annual averages of nitrogen dioxide (NO₂), fine particulate matter (PM_2.5), PM_2.5 absorbance (a marker for black carbon), PM_coarse and ultrafine particles up to age 14 assigned at residential addresses with CIMT varied across deciles of CIMT. False discovery rate corrections (FDR, p < 0.05 for statistical significance) were applied for multiple comparisons. We report quantile regression coefficients that correspond to an average change in CIMT (µm) associated with an interquartile range increase in the exposure.

RESULTS: PM_2.5 absorbance exposure at birth was statistically significantly (FDR < 0.05) associated with a 6.23 µm (95% CI: 0.15, 12.3) higher CIMT per IQR increment in PM_2.5 absorbance in the 10th quantile of CIMT but was not significantly related to other deciles within the CIMT distribution. For NO₂ exposure we found similar effect sizes to PM_2.5 absorbance, but with much wider confidence intervals. PM_2.5 exposure was weakly positively associated with CIMT while PM_coarse and ultrafine did not display any consistent patterns.

CONCLUSIONS: Early childhood exposure to ambient air pollution was suggestively associated with the CIMT distribution during adolescence. Since CIMT increases with age, mitigation strategies to reduce traffic-related air pollution early in life could possibly delay atherosclerosis and subsequently CVD development later in life.

PMID:35576730 | DOI:10.1016/j.envint.2022.107285

ESMO Open. 2022 May 13;7(3):100488. doi: 10.1016/j.esmoop.2022.100488. Online ahead of print.

ABSTRACT

BACKGROUND: Testicular cancer survivors are at risk for cardiovascular disease, often preceded by early development of cardiovascular risk factors due to chemotherapeutic treatment. Therefore, close collaboration between oncologists and primary care physicians (PCPs) is needed during follow-up to monitor and manage cardiovascular risk factors. We designed a shared-care survivorship program, in which testicular cancer patients visit both their oncologist and their PCP. The objective of this study was to test the safety and feasibility of shared-care follow-up after treatment for metastatic testicular cancer.

PATIENTS AND METHODS: The study was designed as an observational cohort study with a stopping rule to check for the safety of follow-up. Safety boundaries were defined for failures in the detection of signals indicating cancer recurrence. Secondary outcomes were the proportion of carried out cardiovascular risk assessments, psychosocial status and patient preferences measured with an evaluation questionnaire.

RESULTS: One hundred and sixty-two patients were enrolled (69% of eligible testicular cancer patients). Almost all (99%, n = 150) PCPs of the enrolled patients agreed to participate in the study. In total, 364 primary care visits took place. No failures occurred in the detection of relapsed testicular cancer. Four follow-up visits were considered as failures because of organizational issues, without activation of the stopping rule. Eventually, the safe boundary was crossed indicating that this shared-care model is a safe alternative for follow-up after testicular cancer. Patients were satisfied with the knowledge level of PCPs. PCPs were willing to further extend their role in follow-up care after cancer.

CONCLUSIONS: Shared-care follow-up is safe and feasible in this patient population. Patients benefit from personalized care, partly close to their home. Within shared care, PCPs can have an important role in cardiovascular risk management and psychosocial survivorship issues.

PMID:35576694 | DOI:10.1016/j.esmoop.2022.100488

Aesthet Surg J. 2022 May 16:sjac122. doi: 10.1093/asj/sjac122. Online ahead of print.

ABSTRACT

BACKGROUND: For decades, facial fat grafting is used in clinical practice for volume restoration. The main challenge of this technique is the variable volume retention. Over the past years, studies reported the addition of supplements to augment the fat graft to increase volume retention.

OBJECTIVES: The aim of this systematic review was to investigate which supplements increase volume retention in facial fat grafting as assessed with volumetric outcomes and patient satisfaction.

METHODS: Central, MEDLINE, EMBASE, Web of Science Core Collection and Google Scholar were searched until 30th of November 2020. Only studies assessing volume after facial fat grafting with supplementation in human subjects were included. Outcomes of interest were volume or patient satisfaction. Quality of the studies was assessed using the Effective Public Health Practice Project tool.

RESULTS: After duplicates were removed 3724 studies were screened by title and abstract. After reading 95 full-text articles, 27 studies were eligible and included for comparison. Supplementation comprised of platelet rich plasma (PRP), platelet rich fibrin, adipose tissue-derived stromal cells or bone marrow-derived stromal cells, cellular or tissue stromal vascular fraction (SVF) or nanofat. In 13 out of 22 studies the supplemented group showed improved volumetric retention and 5 out of 16 studies showed greater satisfaction. The scientific quality of the studies was rated as weak for 20 of 27 studies, moderate for 6 of 27 studies and strong for 1 study.

CONCLUSIONS: Our results show that it remains unclear if additives contribute to facial fat graft retention while there is a need to standardize methodology.

PMID:35576617 | DOI:10.1093/asj/sjac122

J Hand Surg Eur Vol. 2022 Jun;47(6):677-680. doi: 10.1177/17531934221095377.

NO ABSTRACT

PMID:35575276 | DOI:10.1177/17531934221095377

J Am Heart Assoc. 2022 May 17;11(10):e024060. doi: 10.1161/JAHA.121.024060. Epub 2022 May 16.

ABSTRACT

Background Strategies to improve long-term prediction of heart failure and death in valvular surgery are urgently needed because of an increasing number of procedures globally. This study sought to report the prevalence, changes, and prognostic implications of concomitant hepatorenal dysfunction and malnutrition in valvular surgery. Methods and Results In 909 patients undergoing valvular surgery, 3 groups were defined based on hepatorenal function (the modified model for end-stage liver disease excluding international normalized ratio score) and nutritional status (Controlling Nutritional Status score): normal hepatorenal function and nutrition (normal), hepatorenal dysfunction or malnutrition alone (mild), and concomitant hepatorenal dysfunction and malnutrition (severe). Overall, 32%, 46%, and 19% of patients were classified into normal, mild, and severe groups, respectively. Over a 4.1-year median follow-up, mild and severe groups incurred a higher risk of mortality (hazard ratio [HR], 3.17 [95% CI, 1.40-7.17] and HR, 9.30 [95% CI, 4.09-21.16], respectively), cardiovascular death (subdistribution HR, 3.29 [95% CI, 1.14-9.52] and subdistribution HR, 9.29 [95% CI, 3.09-27.99]), heart failure hospitalization (subdistribution HR, 2.11 [95% CI, 1.25-3.55] and subdistribution HR, 3.55 [95% CI, 2.04-6.16]), and adverse outcomes (HR, 2.11 [95% CI, 1.25-3.55] and HR, 3.55 [95% CI, 2.04-6.16]). Modified model for end-stage liver disease excluding international normalized ratio and controlling nutritional status scores improved the predictive ability of European System for Cardiac Operative Risk Evaluation (area under the curve: 0.80 versus 0.73, P<0.001) and Society of Thoracic Surgeons score (area under the curve: 0.79 versus 0.72, P=0.004) for all-cause mortality. One year following surgery (n=707), patients with persistent concomitant hepatorenal dysfunction and malnutrition (severe) experienced worse outcomes than those without. Conclusions Concomitant hepatorenal dysfunction and malnutrition was frequent and strongly linked to heart failure and mortality in valvular surgery.

PMID:35574957 | DOI:10.1161/JAHA.121.024060

ACS Macro Lett. 2022 Jan 18;11(1):20-25. doi: 10.1021/acsmacrolett.1c00647. Epub 2021 Dec 14.

ABSTRACT

Frozen complex coacervate core micelles (C3Ms) were developed as a class of particle stabilizers for Pickering emulsions. The C3Ms are composed of a core of electrostatically interacting weak polyelectrolytes, poly(acrylic acid) (pAA) and poly(dimethylaminopropylacrylamide) (pDMAPAA), surrounded by a corona of water-soluble and surface active poly(N-isopropylacrylamide) (pNiPAM). Mixing parameters of the two polymer solutions, including pH, mixing method, charge ratio, and salinity of the medium, were carefully controlled, leading to monodisperse, colloidally stable C3Ms. A combination of dynamic light scattering and proton nuclear magnetic resonance experiments showed that the C3Ms gradually disassembled from a dynamically frozen core state in pure water into free polyelectrolyte chains above 0.8 M NaCl. Upon formulation of dodecane-in-water emulsions, the frozen C3Ms adsorb as particles at the droplet interfaces in striking contrast with most of the conventional micelles made of amphiphilic block copolymers which fall apart at the interface. Eventually, increasing the salt concentration of the system triggered disassembly of the C3Ms, which led to emulsion destabilization.

PMID:35574801 | PMC:PMC8772379 | DOI:10.1021/acsmacrolett.1c00647

ACS Macro Lett. 2022 Jan 18;11(1):15-19. doi: 10.1021/acsmacrolett.1c00645. Epub 2021 Dec 14.

ABSTRACT

The ultrasound-mediated activation of drugs from macromolecular architectures using the principles of polymer mechanochemistry (sonopharmacology) is a promising strategy to gain spatiotemporal control over drug activity. Yet, conceptual challenges limit the applicability of this method. Especially low drug-loading content and low mechanochemical efficiency require the use of high carrier mass concentrations and prolonged exposure to ultrasound. Moreover, the activated drug is generally shielded by the hydrodynamic coil of the attached polymer fragment leading to a decreased drug potency. Here we present a carrier design for the ultrasound-induced activation of vancomycin, which is deactivated with its H-bond-complementary peptide target sequence. We show that the progression from mechanophore-centered linear chains to mechanophore-decorated polymer brushes increases drug-loading content, mechanochemical efficiency, and drug potency. These results may serve as a design guideline for future endeavors in the field of sonopharmacology.

PMID:35574800 | DOI:10.1021/acsmacrolett.1c00645

J Exp Biol. 2022 May 16:jeb.243205. doi: 10.1242/jeb.243205. Online ahead of print.

ABSTRACT

The capacity to deal with external and internal challenges is thought to affect fitness, and the age-linked impairment of this capacity defines the ageing process. Using a recently developed intra-peritoneal glucose tolerance test (GTT) in zebra finches, we tested for a link between the capacity to regulate glucose levels and survival. We also investigated for the effects of ambient factors, age, sex, and manipulated developmental and adult conditions (i.e. natal brood size and foraging cost, in a full factorial design) on glucose tolerance. Glucose tolerance was quantified using the incremental 'area under the curve' (AUC), with lower values indicating higher tolerance. Glucose tolerance predicted survival probability in old birds, above the median age, with individuals with higher glucose tolerance showing better survival than individuals with low or intermediate glucose tolerance. In young birds there was no association between glucose tolerance and survival. Experimentally induced adverse developmental conditions did not affect glucose tolerance, but low ambient temperature at sampling and hard foraging conditions during adulthood induced a fast return to baseline levels (i.e. high glucose tolerance). These findings can be interpreted as an efficient return to baseline glucose levels when energy requirements are high, with glucose presumably being used for energy metabolism or storage. Glucose tolerance was independent of sex. Our main finding that old birds with higher glucose tolerance had better survival supports the hypothesis that the capacity to efficiently cope with a physiological challenge predicts lifespan, at least in old birds.

PMID:35574668 | DOI:10.1242/jeb.243205

Inorg Chem. 2022 May 15. doi: 10.1021/acs.inorgchem.2c00602. Online ahead of print.

ABSTRACT

Recent desires to develop environmentally benign procedures for electrophilic chlorinations have encouraged researchers to take inspiration from nature. In particular, the enzyme chloroperoxidase (CPO), which is capable of electrophilic chlorinations through the umpolung of chloride by oxidation with hydrogen peroxide (H₂O₂), has received lots of attention. CPO itself is unsuitable for industrial use because of its tendency to decompose in the presence of excess H₂O₂. Biomimetic complexes (CPO active-site mimics) were then developed and have been shown to successfully catalyze electrophilic chlorinations but are too synthetically demanding to be economically viable. Reported efforts at generating the putative active chlorinating agent of CPO (an iron hypochlorite species) via the umpolung of chloride and using simple meso-substituted iron porphyrins were unsuccessful. Instead, a meso-chloroisoporphyrin intermediate was formed, which was shown to be equally capable of performing electrophilic chlorinations. The current developments toward a potential method involving this novel intermediate for environmentally benign electrophilic chlorinations are discussed. Although this novel pathway no longer follows the mechanism of CPO, it was developed from efforts to replicate its function, showing the power that drawing inspiration from nature can have.

PMID:35574587 | DOI:10.1021/acs.inorgchem.2c00602

Minerva. 2022 May 9:1-20. doi: 10.1007/s11024-022-09467-8. Online ahead of print.

ABSTRACT

In this paper, we bring together the literature on citizen science and on deliberative democracy and epistemic injustice. We argue that citizen science can be seen as one element of "deliberative systems," as described by Mansbridge et al. But in order to fulfil its democratic potential, citizen science needs to be attentive to various forms of exclusion and epistemic injustice, as analyzed by Fricker, Medina and others. Moreover, to tap the potentials of citizen science from the perspective of deliberative democracy, it needs to move towards a more empowered approach, in which citizens do not only deliver data points, but also, in invited or uninvited settings, participate in discussions about the goals and implications of research. Integrating citizen science into the deliberative systems approach embeds it in a broader framework of democratic theory and suggests the transmission of certain practical strategies (e.g., randomized sampling). It can also contribute to realism about both the potentials and the limits of citizen science. As part of a deliberative system, citizen science cannot, and need not, be the only place in which reforms are necessary for creating stronger ties between science and society and for aligning science with democratic values.

PMID:35574292 | PMC:PMC9080978 | DOI:10.1007/s11024-022-09467-8

Bioact Mater. 2022 Apr 23;19:292-327. doi: 10.1016/j.bioactmat.2022.04.008. eCollection 2023 Jan.

ABSTRACT

Fabrication of functional scaffolds for tissue engineering and regenerative medicine applications requires material systems with precise control over cellular performance. 3D printing is a powerful technique to create highly complex and multicomponent structures with well-defined architecture and composition. In this review paper, we explore extrusion-based 3D printing methods (EBP, i.e., Near Field Electrospinning (NFES), Melt Electrowriting (MEW), Fused Deposition Modeling (FDM), and extrusion bioprinting) in terms of their ability to produce scaffolds with bio-instructive properties. These material systems provide spatio-temporal guidance for cells, allowing controlled tissue regeneration and maturation. Multiple physical and biochemical cues introduced to the EBP scaffolds are evaluated in their ability to direct cell alignment, proliferation, differentiation, specific ECM production, and tissue maturation. We indicate that the cues have different impacts depending on the material system, cell type used, or coexistence of multiple cues. Therefore, they must be carefully chosen based on the targeted application. We propose future directions in bio-instructive materials development, including such concepts as metamaterials, hybrid living materials, and 4D printing. The review gathers the knowledge essential for designing new materials with a controlled cellular response, fabrication of advanced engineered tissue, and developing a better understanding of cell biology, especially in response to the biomaterial.

PMID:35574057 | PMC:PMC9058956 | DOI:10.1016/j.bioactmat.2022.04.008

J Popul Econ. 2022 May 7:1-24. doi: 10.1007/s00148-022-00904-2. Online ahead of print.

ABSTRACT

When the European Union expanded eastward in 2004 and 2007 to accession the so-called EU8 and EU2 countries, respectively, the incumbent member states imposed temporary restrictions on the employment of EU8 and EU2 nationals. Self-employed individuals were exempted from these transitional arrangements, prompting concerns that self-employment could be used as a means to evade the restrictions on labour market access. If the transitional arrangements led to an increase in EU8 and EU2 nationals' self-employment rates, as previous research suggests, then their removal should have led to a corresponding decrease. This article analyses whether the latter has indeed been the case. Using pooled cross section data from the EU Labour Force Survey, over the period 2004-2019, we show that removing the transitional arrangements has had a negative effect on the self-employment rates of EU2 nationals, but seemingly no effect on the self-employment rates of EU8 nationals. Distinguishing between types of capitalist regimes, however, reveals a much more nuanced picture, with significant variation in terms of the magnitude and significance of the effect across groups of countries.

PMID:35573469 | PMC:PMC9077354 | DOI:10.1007/s00148-022-00904-2

Front Psychiatry. 2022 Apr 27;13:879491. doi: 10.3389/fpsyt.2022.879491. eCollection 2022.

ABSTRACT

Alzheimer's disease (AD) is a global public health priority as with aging populations, its prevalence is expected to rise even further in the future. The brain and gut are in close communication through immunological, nervous and hormonal routes, and therefore, probiotics are examined as an option to influence AD hallmarks, such as plaques, tangles, and low grade inflammation. This study aimed to provide an overview of the available animal evidence on the effect of different probiotics on gut microbiota composition, short chain fatty acids (SCFAs), inflammatory markers, Amyloid-β (Aβ), and cognitive functioning in AD animal models. A systematic literature search was performed in PubMed, SCOPUS, and APA PsychInfo. Articles were included up to May 2021. Inclusion criteria included a controlled animal study on probiotic supplementation and at least one of the abovementioned outcome variables. Of the eighteen studies, most were conducted in AD male mice models (n = 9). Probiotics of the genera Lactobacillus and Bifidobacterium were used most frequently. Probiotic administration increased species richness and/or bacterial richness in the gut microbiota, increased SCFAs levels, reduced inflammatory markers, and improved cognitive functioning in AD models in multiple studies. The effect of probiotic administration on Aβ remains ambiguous. B. longum (NK46), C. butyricum, and the mixture SLAB51 are the most promising probiotics, as positive improvements were found on almost all outcomes. The results of this animal review underline the potential of probiotic therapy as a treatment option in AD.

PMID:35573324 | PMC:PMC9094066 | DOI:10.3389/fpsyt.2022.879491

Front Neurosci. 2022 Apr 27;16:851463. doi: 10.3389/fnins.2022.851463. eCollection 2022.

ABSTRACT

REASON FOR PERFORMING STUDY: So far, only transcranial motor evoked potentials (MEP) of the extensor carpi radialis and tibialis cranialis have been documented for diagnostic evaluation in horses. These allow for differentiating whether lesions are located in either the thoraco-lumbar region or in the cervical myelum and/or brain. Transcranial trapezius MEPs further enable to distinguish between spinal and supraspinal located lesions. No normative data are available. It is unclear whether transcranial electrical stimulation (TES) and transcranial magnetic stimulation (TMS) are interchangeable modalities.

OBJECTIVES: To provide normative data for trapezius MEP parameters in horses for TES and TMS and to discern direct and indirect conduction routes by neurophysiological models that use anatomical geometric characteristics to relate latency times with peripheral (PCV) and central conduction velocities (CCV).

METHODS: Transcranial electrical stimulation-induced trapezius MEPs were obtained from twelve horses. TES and TMS-MEPs (subgroup 5 horses) were compared intra-individually. Trapezius MEPs were measured bilaterally twice at 5 intensity steps. Motoneurons were localized using nerve conduction models of the cervical and spinal accessory nerves (SAN). Predicted CCVs were verified by multifidus MEP data from two horses referred for neurophysiological assessment.

RESULTS: Mean MEP latencies revealed for TES: 13.5 (11.1-16.0)ms and TMS: 19.7 (12-29.5)ms, comprising ∼100% direct routes and for TMS mixed direct/indirect routes of L:23/50; R:14/50. Left/right latency decreases over 10 > 50 V for TES were: -1.4/-1.8 ms and over 10 > 50% for TMS: -1.7/-3.5 ms. Direct route TMS-TES latency differences were 1.88-4.30 ms. 95% MEP amplitudes ranges for TES were: L:0.26-22 mV; R:0.5-15 mV and TMS: L:0.9 - 9.1 mV; R:1.1-7.9 mV.

CONCLUSION: This is the first study to report normative data characterizing TES and TMS induced- trapezius MEPs in horses. The complex trapezius innervation leaves TES as the only reliable stimulation modality. Differences in latency times along the SAN route permit for estimation of the location of active motoneurons, which is of importance for clinical diagnostic purpose. SAN route lengths and latency times are governed by anatomical locations of motoneurons across C2-C5 segments. TES intensity-dependent reductions of trapezius MEP latencies are similar to limb muscles while MEP amplitudes between sides and between TES and TMS are not different. CCVs may reach 180 m/s.

PMID:35573305 | PMC:PMC9094044 | DOI:10.3389/fnins.2022.851463

Front Neurosci. 2022 Apr 29;16:838711. doi: 10.3389/fnins.2022.838711. eCollection 2022.

ABSTRACT

Breastfeeding (duration) can be positively associated with infant growth outcomes as well as improved cognitive functions during childhood and later life stages. (Prolonged) exposure to optimal lipid quantity and quality, i.e., the supramolecular structure of lipids, in mammalian milk, may contribute to these beneficial effects through nutritional early-life programming. In this pre-clinical study, we exposed male C57BL/6J mice from post-natal Days 16 to 42 (i.e., directly following normal lactation), to a diet with large lipid droplets coated with bovine milk fat globule membrane-derived phospholipids, which mimic more closely the supramolecular structure of lipid droplets in mammalian milk. We investigated whether exposure to this diet could affect growth and brain development-related parameters. As these outcomes are also known to be affected by the post-weaning social environment in mice, we included both individually housed and pair-wise housed animals and studied whether effects of diet were modulated by the social environment. After Day 42, all the animals were fed standard semi-synthetic rodent diet. Growth and body composition were assessed, and the mice were subjected to various behavioral tests. Individual housing attenuated adolescent growth, reduced femur length, and increased body fat mass. Adult social interest was increased due to individual housing, while cognitive and behavioral alterations as a result of different housing conditions were modest. The diet increased adolescent growth and femur length, increased lean body mass, reduced adolescent anxiety, and improved adult cognitive performance. These effects of diet exposure were comparable between individually and socially housed mice. Hence, early life exposure to a diet with lipid droplets that mimic the supramolecular structure of those in mammalian milk may improve adolescent growth and alters brain function in both socially and individually housed mice. These findings suggest that lipid structure in infant milk formula may be a relevant target for nutritional solutions, targeting both healthy infants and infants facing growth challenges.

PMID:35573304 | PMC:PMC9099012 | DOI:10.3389/fnins.2022.838711