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There is emerging empirical evidence indicating that differences in self‐reported sensory processing may be associated with differences in levels of stress in the adult populations. Understanding how sensory processing relates to stress is of clinical relevance, given the well‐established impact of stress on physical health, mental health and well‐being. Although several studies have examined the association between sensory processing and stress in adult populations, no published reviews have systematically summarised and synthesised these findings. We aimed to fill this gap by conducting a systematic review to synthesise the available evidence examining the association between self‐reported sensory processing and self‐reported measures of stress in the adult population. The review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA‐S) checklist. Twenty studies were included in the final review. Quality assessment was conducted with the Mixed Methods Appraisal Tool. Overall, the evidence is strong for an association between differences in sensory processing and self‐reported stress in adults. This association was found across a range of populations and measures of stress, in cross‐sectional studies. The most commonly used measure of sensory processing was the Highly Sensitive Person Scale, which was consistently moderately associated with a range of measures of stress. The quality of the included studies was generally good, with most meeting four or five out of five criteria. Longitudinal studies are lacking. There is strong evidence for a cross‐sectional association between sensory processing and stress in an adult population. Further research, in particular longitudinal studies and studies including clinical populations, would be of benefit in order to establish causality. [ABSTRACT FROM AUTHOR]

Introduction: This work describes a secondary analysis of a qualitative data set originally used to understand parent participants' preferences for the design and implementation of a screening programme for paediatric Type 1 diabetes (T1D). From this, their spontaneous preferences for peer support emerged, described here in the context of existing peer support programmes for the newly diagnosed alongside suggestions for their incorporation into screening programmes for T1D and a range of other conditions. Methods: Data were collected from semi‐structured interviews conducted with parents of children aged 3–13 years to explore their expectations, perceptions and preferences of a T1D paediatric screening programme. A secondary analysis of interviews from participants who spontaneously raised preferences for peer support was used to populate a novel framework informed by NHS England's key principles for the same, namely, Shared experiences and reciprocated support, Accessibility and inclusivity and Person‐centred and integrated peer support. Results: Parents in 29 of 33 interviews spontaneously described the potential value of peer support if receiving a result indicating a positive (presymptomatic T1D result) from a screening programme. Specifically, the value of 'Shared experiences and reciprocated support' in terms of emotional support and reassurance, and access to more directly interpretable and relevant information related to the condition; 'Accessibility and inclusivity' relating to access to a community of similar individuals, whether in person or online; 'Person‐centred and integrated peer‐support' and the need for support reflecting the changing need of the child and the integration of peer support with clinical care. Conclusions: The needs of peer support described by parents involved in T1D paediatric screening appear to be shared with those of families with children diagnosed with a range of life‐altering conditions. Although the needs of peer support for paediatric screening may differ across conditions, our findings are a valuable starting point for its design both in T1D and other examples of similar population screening programmes. Patient or Public Contribution: Patients and the public have been involved throughout the design of the ELSA study and have worked with us to inform the study process. They contributed to the design and content of patient‐facing materials, the content of our topic guides and the analysis and interpretation of our findings. [ABSTRACT FROM AUTHOR]

Despite growing concern about climate change, there remains a significant gap between individuals' environmental concern and their actual behaviour. Humans' personal relationship with nature is a key contributor to pro‐environmental behaviour (PEB), which may account for this gap. Those individuals with high levels of sensory processing sensitivity (SPS), approximately 25%–30% of the population, have a particularly strong connection with the natural world and have a 'pause to check' attitude that may make them more prone to consider future consequences of actions. We hypothesise that (1) a disposition to experience awe, characterizing high SPS, mediates the association between the trait and connectedness to nature (CN); (2) SPS is associated with PEB, and CN mediates the association; and (3) consideration for future consequences also mediates the association between high SPS and PEB.807 participants completed an online survey including validated measures of SPS, CN, awe, PEB and consideration for future consequences. Correlational and mediational analyses were performed to test the hypotheses.The study showed that the relationship between SPS and CN was mediated by awe. The relationship between SPS and PEB was independently mediated by CN and consideration for future consequences.Policy implications. The UN Sustainable Development Goals were set to reduce inequalities (SDG 10) by considering individual differences, as well as improving climate action (SDG 13). This study shows that psychological dimensions such as sensory processing sensitivity (SPS) are linked to pro‐environmental behaviour (PEB) through future‐oriented thinking and feeling connected with nature. These results also suggest that cultivating connectedness to nature and training those with lower SPS to consider future consequences of actions may be a potential avenue to improve PEB. Read the free Plain Language Summary for this article on the Journal blog. Read the free Plain Language Summary for this article on the Journal blog. [ABSTRACT FROM AUTHOR]

Aims: Dilated cardiomyopathy (DCM) with arrhythmic phenotype combines phenotypical aspects of DCM and predisposition to ventricular arrhythmias, typical of arrhythmogenic cardiomyopathy. The definition of DCM with arrhythmic phenotype is not universally accepted, leading to uncertainty in the identification of high‐risk patients. This study aimed to assess the prognostic impact of arrhythmic phenotype in risk stratification and the correlation of arrhythmic markers with high‐risk arrhythmogenic gene variants in DCM patients. Methods and results: In this multicentre study, DCM patients with available genetic testing were analysed. The following arrhythmic markers, present at baseline or within 1 year of enrolment, were tested: unexplained syncope, rapid non‐sustained ventricular tachycardia (NSVT), ≥1000 premature ventricular contractions/24 h or ≥50 ventricular couplets/24 h. LMNA, FLNC, RBM20, and desmosomal pathogenic or likely pathogenic gene variants were considered high‐risk arrhythmogenic genes. The study endpoint was a composite of sudden cardiac death and major ventricular arrhythmias (SCD/MVA). We studied 742 DCM patients (45 ± 14 years, 34% female, 410 [55%] with left ventricular ejection fraction [LVEF] <35%). During a median follow‐up of 6 years (interquartile range 1.6–12.1), unexplained syncope and NSVT were the only arrhythmic markers associated with SCD/MVA, and the combination of the two markers carried a significant additive risk of SCD/MVA, incremental to LVEF and New York Heart Association class. The probability of identifying an arrhythmogenic genotype rose from 8% to 30% if both early syncope and NSVT were present. Conclusion: In DCM patients, the combination of early detected NSVT and unexplained syncope increases the risk of life‐threatening arrhythmic outcomes and can aid the identification of carriers of malignant arrhythmogenic genotypes. [ABSTRACT FROM AUTHOR]

Aims: 'Hot phases', characterized by chest pain and troponin release, may represent the first clinical presentation of arrhythmogenic cardiomyopathies. Differential diagnosis with acute myocarditis is an unmet challenge for the clinicians. We sought to investigate histological and genetic features in patients with cardiomyopathy presenting with hot phases. Methods and results: We evaluated a case series of consecutive patients hospitalized for suspected 'hot‐phase cardiomyopathy' in two Italian centres from June 2017 to March 2022 (median follow‐up 18 months) that underwent both endomyocardial biopsy (EMB) and genetic testing. Apoptosis was confirmed with TUNEL assay. Among the 17 enrolled patients (mean age 34 ± 15 years, 76% male), only six patients (35%) presented standard histological and immunohistochemical markers for significant cardiac inflammation at EMB. Conversely, apoptosis was found in 13 patients (77%). Genetic testing was positive for a pathogenic/likely pathogenic (P/LP) variant in genes involved in cardiomyopathies (most frequently in DSP) in eight patients (48%), rising to 62% among patients with apoptosis on EMB. Notably, all patients without apoptosis tested negative for P/LP disease‐related variants. Left ventricular ejection fraction was lower in patients showing apoptosis at EMB compared to those without (p = 0.003). Conclusions: Apoptosis, rather than significant inflammation, was mostly prevalent in this case series of patients with 'hot‐phase' presentation, especially in carriers of variants in cardiomyopathy‐related genes. Detecting apoptosis on EMB might guide clinicians in performing genetic testing and in more tailored therapeutic choices in 'hot‐phase cardiomyopathy'. [ABSTRACT FROM AUTHOR]

There is evidence that cardiovascular function can influence sensory processing and cognition, which are known to change with age. However, whether the precision of unisensory and multisensory temporal perception is influenced by cardiovascular activity in older adults is uncertain. We examined whether seated resting heart rate (RHR) was associated with unimodal visual and auditory temporal discrimination as well as susceptibility to the audio‐visual Sound Induced Flash Illusion (SIFI) in a large sample of older adults (N = 3232; mean age = 64.17 years, SD = 7.74, range = 50–93; 56% female) drawn from The Irish Longitudinal Study on Ageing (TILDA). Faster seated RHR was associated with better discretization of two flashes (but not two beeps) and increased SIFI susceptibility when the audio‐visual stimuli were presented close together in time but not at longer audio‐visual temporal offsets. Our findings suggest a significant relationship between cardiovascular activity and the precision of visual and audio‐visual temporal perception in older adults, thereby providing novel evidence for a link between cardiovascular function and perceptual function in aging. We present novel evidence for a relationship between resting heart rate and visual and audio‐visual temporal precision in older adults. This indicates that the cardiovascular and perceptual systems, both of which change with age and are associated with broader physical and cognitive health, are interlinked in aging. [ABSTRACT FROM AUTHOR]

Purpose: Naloxegol has been shown to be an efficient alternative to treat opioid‐induced constipation (OIC). This study aimed at describing the characteristics of naloxegol users and assessing patterns of naloxegol use and associated factors. Methods: This drug utilization cohort study used observational registry data on patients newly prescribed naloxegol in four European countries. Patient characteristics and patterns of naloxegol use and associated factors were described. Results: A total of 17 254 naloxegol users were identified across the countries. Their median age was 56–71 years, and each country had a majority of women (ranging 57.5%–62.9%). Multiple comorbidities, including cancer, were common. Natural opium alkaloids and osmotically acting laxatives (excluding saline) were the most frequently used opioids and laxatives. Overall prior use of opioids ranged from 91.9% to 99.6% and overall prior use of laxatives ranged from 69.9% to 92.4%. Up to 77.7% had prior use of medications with interaction potential, and up to 44.5% used them concurrently with naloxegol. Naloxegol was discontinued by 55.1%–90.9% of users, typically during the first 30 days. Approximately 10%–30% switched to or augmented the treatment with another constipation medication or restarted naloxegol after discontinuation. Augmentation with another constipation medication was relatively common, suggesting that naloxegol was used for multifactorial constipation. Conclusion: The present study reflects real‐world clinical use of naloxegol, including in vulnerable patient groups. Some naloxegol users lacked laxative or regular opioid use within six months before index date or used naloxegol concomitantly with medications presenting an interaction potential. [ABSTRACT FROM AUTHOR]

Background: Sperm deoxyribonucleic acid (DNA) fragmentation is commonly encountered in spermatozoa, and the oocyte assumes responsibility for repairing sperm DNA fragmentation during the oocyte–embryo transition. Objectives: This study aimed to investigate whether the effect of sperm DNA fragmentation on intracytoplasmic sperm injection outcomes depends on the incidence of oocyte dimorphisms. Materials and methods: For the present cohort, 2942 fertilized oocytes from 525 patients submitted to intracytoplasmic sperm injection cycles were assessed. The present study was conducted in a private in vitro fertilization center affiliated to a university from June 2016 to July 2019. Semen samples were divided into the following two groups depending on the sperm DNA fragmentation index: a low fragmentation index group (<30% sperm DNA fragmentation, n = 1468) and a high fragmentation index group (≥30% sperm DNA fragmentation, n = 486). In addition, mature oocytes were examined before sperm injection, and intracytoplasmic and extracytoplasmic defects were recorded. The effect of the sperm DNA fragmentation index on laboratory and clinical intracytoplasmic sperm injection outcomes (depending on the presence of oocyte defects) was evaluated. Results: Significant increases in the rates of fertilization, high‐quality embryo, implantation, and pregnancy were noted for cycles with <30% sperm DNA fragmentation than cycles with ≥30% sperm DNA fragmentation (regardless of the presence of oocyte dimorphisms). The presence of dimorphisms significantly impacted laboratory and clinical outcomes. The lowest fertilization and high‐quality embryo rates were observed when a high sperm DNA fragmentation index was associated with the presence of dark cytoplasm, vacuoles, resistant membrane, and non‐resistant membrane. The lowest implantation and pregnancy rates were observed when a high sperm DNA fragmentation index was associated with the presence of vacuoles, defective perivitelline space, and fragmented polar body. The effect of sperm DNA fragmentation on miscarriage rates was significantly influenced by the presence of centrally located cytoplasmic granulation, a defective perivitelline space and non‐resistant membrane. Conclusion: A high sperm DNA fragmentation index increases the likelihood of miscarriage in intracytoplasmic sperm injection cycles, an effect that may potentially be magnified by the presence of oocyte dysmorphisms. [ABSTRACT FROM AUTHOR]

This article discusses the intersection between coronary artery disease (CAD) and dilated cardiomyopathy (DCM), two distinct heart diseases. The authors highlight the importance of considering the coexistence of these conditions and the potential impact on prognosis and treatment strategies. The study analyzes the prevalence and prognostic implications of genetic and phenotypic features in patients with stable CAD. The findings suggest that DCM pathogenic variants can affect left ventricular remodeling and outcomes in CAD patients, while non-ischemic myocardial scar does not affect prognosis. The study emphasizes the need for further research and larger multicenter studies to fully understand the relationship between these diseases. [Extracted from the article]

While there is evidence for the effects of positive psychology interventions (PPIs) in the Western world, we know little about their effects on Arab cultures. This review aimed to assess the effects of PPIs on well‐being and mental health across Arab countries. Systematic searches of randomised controlled trials (RCTs) and quasi‐experimental studies investigating PPIs in Arabia were conducted in six English and Arabic databases from the inception of positive psychology in 1998 to 28 February 2022. The quality of the studies was assessed using the Cochrane risk‐of‐bias tools. The protocol was published in the BMJ Open. Forty‐four studies from 10 Arab countries (n = 3598 participants) were included. Of these, 12 were RCTs and 32 were quasi‐experimental. The studies mainly focused on adults (73%) and healthy populations (86%). PPIs included mindfulness, positive thinking, strengths, hope, optimism, self‐compassion, positive traits, and multiple PPIs. Nearly all studies (91%) mentioned cultural adaptation; however, little detail was given. This is the first review in Arabia. PPIs appear to be effective for promoting well‐being and reducing mental health issues. However, there were some risks of bias concerns. Future research should include younger and clinical populations, using larger samples and providing more details about adaptation. [ABSTRACT FROM AUTHOR]

Aim: To assess the efficacy of intravenous ferric carboxymaltose (IV FCM) for the treatment of iron deficiency anemia (IDA) diagnosed de novo in the third trimester of pregnancy. Methods: Case–control study conducted in pregnant women with IDA newly diagnosed in the third trimester of pregnancy. Women treated with a single IV FCM injection were included as cases and those who received daily 210 g of oral ferrous sulphate (FS) as controls. Controls were matched to cases in a 2:1 ratio by basal hemoglobin (Hb) concentration (±0.5 g/dl). Results: A total of 35 cases and 70 controls were included in the study. The mean Hb concentration level significantly increased after iron treatment in both cases (from 9.3 ± 0.8 to 11.1 ± 0.8 g/dl, p < 0.0001) and controls (from 9.6 ± 0.9 to 10.9 ± 1 g/dl, p < 0.0001). The rate of women who exceeded the recommended threshold of 11 g/dl after treatment did not significantly differ between cases (63% (95%CI, 45%–79%)) and controls (56% (95%CI, 44%–68%)) (p = 0.48). Comparison of maternal and neonatal outcomes and adverse effects did not show any significant difference between groups. Conclusions: Our results suggest that IV FCM and oral FS can be considered equally effective in the treatment of IDA newly detected in the third trimester of pregnancy. [ABSTRACT FROM AUTHOR]

COVID‐19 vaccine hesitancy poses serious challenges in achieving adequate vaccine coverage in the general population. While most studies on vaccine hesitance determinants during the COVID‐19 pandemic were quantitative, qualitative research on the reasons for vaccine resistance is still lacking. To fill this gap, this study aims to qualitatively investigate cognitive and emotional factors associated with COVID‐19 vaccine hesitancy. This qualitative pilot study was conducted between October and November 2021 in Italy. A total of 40 COVID‐19 vaccine‐hesitant ("hesitant not vaccinated" or "hesitant but vaccinated") individuals completed anonymous questionnaires with open‐ended questions. Data were analysed using the Interpretive Description approach. The central theme that emerged about vaccine hesitancy was the lack of control. This construct included four different sub‐categories: distrust of the government, infodemic, influence of family, and general anti‐vaccine opinions. The results also showed that the most important emotional and cognitive factors associated with hesitancy were anger related to a perceived sense of oppression; emotional avoidance to minimize risk; anxiety related to potential vaccine side effects. Identifying and understanding factors influencing COVID‐19 vaccination hesitancy is crucial to improving communication strategies that will ultimately result in increased confidence and vaccine acceptance. [ABSTRACT FROM AUTHOR]

This study aims to examine the relationships of managers' compassionate goals with innovation and performance in small‐ and medium‐sized enterprises (SMEs). By integrating social exchange theory with social information processing theory, we hypothesize a serial mediation model in which organizational cooperation and firm innovation sequentially mediate a positive relationship between managers' compassionate goals and firm performance. However, we predict that this positive indirect effect would occur only when managers have low self‐image goals and there is a high innovation‐supportive work environment. Based on survey data from a sample of 116 SMEs in France, our results provide support for our predictions. This study contributes to the literature by disclosing the mechanisms and boundary conditions of the relationship of managers' compassionate goals with SMEs' innovation and performance. Theoretical and managerial implications of this study are discussed. [ABSTRACT FROM AUTHOR]

BACKGROUND: The enzyme β‐galactosidase (EC 3.2.1.2.3) obtained from yeast is produced intracellularly. Cell extraction consists of the treatment of a cell suspension with chemical agents, thus obtaining the enzyme with biological activity. After obtaining the extracted enzyme, it is concentrated by ultrafiltration and dried. Lyophilization can be used in this step. The objective of this work was to study the production and extraction of β‐galactosidase from Saccharomyces fragilis IZ 275 using lactose from cheese whey. RESULTS: Under optimum extraction conditions, 2% (v/v) chloroform, 37 °C for 6 h of extraction, 35% of lactose hydrolysis was achieved using 1% (v/v) β‐galactosidase during 10 h of hydrolysis. Extracted enzyme activity resulted in 81% lactose hydrolysis using 12% (v/v) enzyme at pH 6.0 and 37 °C. Enzymatic kinetics were evaluated using 12% of extracted enzyme in 5 h of hydrolysis reaction, and 100% lactose hydrolysis was obtained. The enzyme activity after extraction, concentration and lyophilization was 100%, 60% and 45.3% of lactose hydrolysis, respectively, after 5 h of hydrolysis reaction at 37 °C and pH 6.0. CONCLUSION: The yeast S. fragilis IZ 275 grown in cheese whey produces intracellular β‐galactosidase and its extraction is efficient with the use of 2% chloroform at 37 °C for 6 h, allowing its use for industrial and pharmaceutical purposes. The extracted enzyme must be used at 37 °C and pH 6.0 at a concentration of 12% (v/v) of enzyme to obtain the total hydrolysis of lactose in 5 h of reaction. © 2022 Society of Chemical Industry (SCI). [ABSTRACT FROM AUTHOR]

The objective of this cross‐sectional study was to investigate the impact of paternal age on the outcomes of intracytoplasmic sperm injection (ICSI) cycles at different values of maternal age. A total of 21,960 injected oocytes deriving from 3837 ICSI cycles performed between January 2014 and October 2020, performed in a private university–affiliated in vitro fertilization centre was included. The main effects of maternal and paternal age, as well as the effect of their product (interaction term) on embryo development and pregnancy outcomes were investigated considering the clustering of data. The coefficients for the interaction term were statistically significant for blastocyst development, top‐quality blastocyst, implantation, pregnancy, miscarriage, and live‐birth rates. For every 1‐year increase in paternal age, the odds ratio of live‐birth reduces by 1% in females aged 37 years, 1.6% in those aged 38 years, 2.4% in 39‐year‐old females, 5% in 42‐year‐old females and so on. An increase in the interaction term by 1 year decreases the pregnancy rate by 0.4% and live‐birth rate by 0.8 and increases the miscarriage rate by 1.2%. The slopes of maternal age on blastulation, blastocyst quality, and implantation, pregnancy, miscarriage, and live‐birth rate significantly changed (worsened) for every year increase in paternal age. [ABSTRACT FROM AUTHOR]

The transition from dividing progenitors to postmitotic motor neurons (MNs) is orchestrated by a series of events, which are mainly studied at the transcriptional level by analyzing the activity of specific programming transcription factors. Here, we identify a post‐transcriptional role of a MN‐specific transcriptional unit (MN2) harboring a lncRNA (lncMN2‐203) and two miRNAs (miR‐325‐3p and miR‐384‐5p) in this transition. Through the use of in vitro mESC differentiation and single‐cell sequencing of CRISPR/Cas9 mutants, we demonstrate that lncMN2‐203 affects MN differentiation by sponging miR‐466i‐5p and upregulating its targets, including several factors involved in neuronal differentiation and function. In parallel, miR‐325‐3p and miR‐384‐5p, co‐transcribed with lncMN2‐203, act by repressing proliferation‐related factors. These findings indicate the functional relevance of the MN2 locus and exemplify additional layers of specificity regulation in MN differentiation. Synopsis: The transition from dividing progenitors to post‐mitotic motor neurons is known to be controlled by the activity of specific transcription factors. Here, the noncoding MN2 locus is identified as a bifunctional modulator of motor neuron differentiation by controlling multiple post‐transcriptional circuitries. The MN2 locus controls the transition of dividing progenitors to post‐mitotic motor neurons (MNs).MN2 function is mediated by expression of both short (miRNA) and long (lncRNA) non‐coding RNAs.The long noncoding RNA lncMN2‐203 promotes MN maturation as a sponge for miR‐466i‐5p and upregulating targets involved in MN differentiation and function.Co‐transcribed miRNAs miR‐325‐3p and miR‐384‐5p repress proliferation gene pathways through the control of cell cycle‐related factors. [ABSTRACT FROM AUTHOR]

Background: Nowadays, pathogenesis of preeclampsia (PE) is still unknown. Among the different etiological hypotheses, some authors proposed that it might be because of an abnormal immunologic response to a foreign fetal antigen derived from the father's spermatozoa. Indeed, the fetus is considered a semi‐allograft, being one half paternally derived in its antigenicity, and the first pathogenic insult of PE may be an abnormal maternal immune response toward this semi‐allogenic implant. In the context of artificial reproductive techniques, it has been shown that the use of donor and surgically retrieved spermatozoa (e.g., testicular sperm extraction [TESE]) increases the risk of PE, confirming the protective effect of sperm exposure on maternal complications. Objective: Determining whether the lack of exposure to sperm antigens is associated with worse maternal and neonatal outcomes in pregnancies obtained through intracytoplasmic sperm injection after TESE (ICSI–TESE) for obstructive azoospermia (OA). Materials and methods: This is a single‐center case–control retrospective study, focusing on all first pregnancies obtained through ICSI–TESE for OA at Humanitas Fertility Center between January 1, 2010 and December 31, 2019. Controls included patients that achieved their first pregnancy with ICSI and ejaculated spermatozoa, for a diagnosis other than azoospermia, in the same time period. Cases were matched with controls in a 1:2 ratio, considering female age, female BMI, and year of controlled ovarian stimulation. The primary outcome measure was the delivery rate, defined as the number of deliveries divided by the total number of clinical pregnancies. Secondary outcome measures focused on maternal and neonatal complications, such as miscarriage rate, rate of main obstetric complications, prematurity rate, and rate of congenital malformations. Results: By analyzing overall 113 pregnancies among cases and 214 pregnancies among controls, this study showed that the delivery rate was higher in controls with respect to cases (92.06% vs. 84.07%, p = 0.026); among deliveries, live births were 98.95% and 100%, respectively, whereas only one stillbirth occurred in cases. The first trimester miscarriage rate was higher in the cases than controls (13.27% vs. 6.07%, p = 0.027), whereas no difference was found among the rate of second trimester miscarriages, therapeutic abortions, and ectopic pregnancies. There was no difference regarding the rate of maternal complications, including gestational hypertension, PE, HELLP syndrome, gestational diabetes, placenta previa, placental abruption, and premature rupture of the membranes. Considering neonatal complications, it was shown that twins belonging to controls had a higher prematurity rate with respect to cases (65.79% vs. 50.00%) but without a statistical relevance. Lastly, the rate of congenital malformations did not differ among the two groups. Discussion: This study showed that, once couples diagnosed with OA achieve a pregnancy, they have a much higher risk of miscarriage in the first trimester in respect to non‐azoospermic patients. Moreover, controls had a higher delivery rate in respect to cases; however, when the fetal status at birth was compared, no difference was found between live births and stillbirths. Conclusions: Differently from the findings in the literature, no association with PE was found. This might be related to a collider bias/left truncation bias: As azoospermic patients are at higher risk of early termination of pregnancy, it results that they do not have the possibility to develop PE and other adverse outcomes. [ABSTRACT FROM AUTHOR]

Aims: The present study investigated the prognostic impact of either isolated left atrial (LA) impairment, or its association with right ventricular (RV) failure, in heart failure (HF) with reduced ejection fraction (HFrEF), using basic and speckle tracking echocardiography (STE). Methods and results: One hundred and six outpatients with HFrEF were enrolled in this prospective observational study. Patients with primary lung diseases, non‐sinus rhythm, previous cardiac surgery, and poor acoustic window were excluded. After clinical examination and basic echocardiography, STE was used to measure peak atrial longitudinal strain (PALS) and a new marker of RV performance and pulmonary circulation relation: free‐wall RV longitudinal strain (fwRVLS)/systolic pulmonary artery pressure (sPAP). Patients were followed for all‐cause/cardiovascular death and HF hospitalization. Of 84 eligible patients (60.1 ± 11.5 years; 82% male patients), 48 reached the combined endpoint (cardiovascular death and/or HF hospitalization). Population was divided into three groups: Group 1 (PALS ≥ 15 and fwRVLS/sPAP ≤ −0.5), Group 2 (PALS ≤ 15 and fwRVLS/sPAP ≤ −0.5), and Group 3 (PALS ≤ 15 and fwRVLS/sPAP > −0.5). Mean follow up was 3.5 ± 0.3 years. The higher severity groups were associated with higher LA volume index (P < 0.0001), New York Heart Association class (P = 0.02), mitral regurgitation (P = 0.0004) and tricuspid regurgitation grades (P < 0.0001), lower left ventricular (LV) ejection fraction (P = 0.0003), LV global longitudinal strain (P < 0.0001), PALS (P < 0.0001), tricuspid annular plane systolic excursion (P < 0.007), sPAP (P < 0.0001), and RV strain (P < 0.0001). Reduced PALS and fwRVLS/sPAP were independent predictors of the combined endpoint with adjusted Cox models (hazard ratio = 9.54; 95% confidence interval = 2.95–30.92; P = 0.0002 for Group 3 vs. Group 1). Kaplan–Meier curves showed early and persistent divergence between the three groups for the prediction of the combined endpoint and of all‐cause death (P < 0.0001). Conclusions: The combination of LA and right heart damage entails worse prognosis in patients with HFrEF. The evaluation of PALS and fwRVLS/sPAP could aid risk stratification of HFrEF patients to provide them early treatment. [ABSTRACT FROM AUTHOR]

The benefits of exposure to nature for health and well‐being have been demonstrated across multiple disciplines. Recent work has sought to establish one 'dose' or type of nature exposure that is universally beneficial, which has proven difficult.We use the principles of psychopharmacology to look beyond the use of dose as a concept for prescribing nature. Instead, we posit a multidimensional model of bioavailability of nature to shift the focus beyond universal effects, and instead consider the relationship between health and nature as dynamic, changeable and heavily contextual.We propose that the bioavailability of nature interactions is constructed through understanding route of administration, dose and concentration.By delineating the mechanisms of health benefit derived from the type of behavioural interaction (through being, doing and living), the route of administration of nature interactions may be highly variable not just between, but also within, individuals.We propose concentration as being a meeting between the subjective aspects of the individual and the subjective qualities of the nature at that specific time and place. We use a 'green equation', for mapping the processes and pathways that belie the interaction between the person and their environment. Here, the nature/health association as a dynamic interaction, and we operationalise this within a multidimensional construct of bioavailability.We provide an overview of this testable model and summarise with preliminary evidence as well as a research agenda for the future. A free Plain Language Summary can be found within the Supporting Information of this article. A free Plain Language Summary can be found within the Supporting Information of this article. [ABSTRACT FROM AUTHOR]

We present the case of a 77‐years‐old man with aortic valve stenosis (AS) and reduced left ventricular ejection fraction, in whom right parasternal view provided the best hemodynamic evaluation of AS severity during dobutamine stress echocardiography [ABSTRACT FROM AUTHOR]

Background: Studies on immunological infertility after inguinal hernia correction are few and not very representative. Anti‐sperm antibodies have been shown to reduce male fertility. Although the extent of infertility due to anti‐sperm antibodies alone is not very clear, data indicates that about 8%–10% of infertile patients have immunological infertility Design: This retrospective study includes all infertile male patients (n = 2258) who underwent mixed antiglobulin reaction tests and urologic examination from 2000 to 2020. Sperm quality (assessed by the number of spermatozoa, their motility, vitality, and normal form) was also evaluated. Among these patients, 191 had previously undergone unilateral or bilateral inguinal hernia surgery repair. The aim of the study is to evaluate if there is a higher incidence of positive mixed antiglobulin reaction test among patients undergoing inguinal hernioplasty compared to the unselected infertile population. Results: Anti‐sperm antibodies would seem to increase in both patients who performed general andrological surgery and groin hernia correction, respectively 3.48 (95% Confidence Interval: 1.70–7.10; p < 0.001) and 2.45 (95% Confidence Interval: 1.01–5.99; p < 0.05) times more than the unselected infertile population. Conclusions: Mixed antiglobulin reaction test could be useful in patients undergone previous scrotal surgery or hernia correction men, to avoid false unexplained infertility diagnoses and to direct the couple to assisted reproductive technology procedures. Basal evaluation of spermatozoa does not actually consider andrological surgery as an indication to autoimmunity investigation. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the impact of male age, semen quality and days of ejaculatory abstinence on embryo morphokinetics. A total of 1,220 zygotes obtained from 139 couples in a private in vitro fertilisation centre were analysed. The timing of specific events from the point of insemination, such as timings to pronuclei appearance and fading, to two, three, four, five, six, seven and eight cells and to blastulation were recorded. Multivariate linear regression analysis was used to evaluate the influence of paternal factors on embryo morphokinetic events. Paternal age was positively correlated with delayed cell cleavage and blastulation, and negatively associated with implantation rate, and clinical pregnancy and live–birth chances. The ejaculatory abstinence was inversely correlated with the implantation rate. Inverse relationships were observed between semen parameters (sperm count, progressive sperm motility, total motile sperm count and morphology) and the timing of specific events during embryo development. Sperm morphology was also positively associated with implantation rate and pregnancy and live–birth chances. Increased paternal age and ejaculatory abstinence, and poor semen quality correlate with delayed cell cleavage and blastulation and negatively impact intracytoplasmic sperm injection outcomes. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID‐19), which causes serious respiratory illnesses such as pneumonia and lung failure, was first reported in mid‐December 2019 in China and has spread around the world. In addition to causing serious respiratory illnesses such as pneumonia and lung failure, there have been conflicting reports about the presence of SARS‐CoV‐2 in the semen of patients who were previously diagnosed with COVID‐19 and possible implications for the male reproductive tract. Objective: The goal for the present study was to review the current status of the literature concerning COVID‐19 and male reproduction. Material and methods: An electronic literature search was done by using PubMed and Google Scholar databases. Relevant papers, concerning SARS‐COV‐2 and COVID‐19 and male reproduction, published between January 2020 and December 2020 were selected, analyzed and eventually included in the present literature review. Results: SARS‐CoV‐2 may infect any cell type expressing angiotensin‐converting enzyme 2 (ACE2), including reproductive cells. Besides the presence of the SARS‐CoV‐2 receptor, the expression of host proteases, such as transmembrane serine protease 2 (TMPRSS2), is needed to cleave the viral S protein, allowing permanent fusion of the viral and host cell membranes. Here, we aimed to review the current status of the literature concerning COVID‐19 and male reproduction. The lack of co‐expression of ACE2 and TMPRSS2 in the testis suggests that sperm cells may not be at increased risk of viral entry and spread. However, the presence of orchitis in COVID‐19‐confirmed patients and compromised sex‐related hormonal balance among these patients intrigues reproductive medicine. Discussion: SARS‐CoV‐2 may use alternate receptors to enter certain cell types, or the expression of ACE2 and TMPRSS2 may not be detected in healthy individuals. Conclusion: COVID‐19 challenges all medical areas, including reproductive medicine. It is not yet clear what effects, if any, the COVID‐19 pandemic will have on male reproduction. Further research is needed to understand the long‐term impact of SARS‐CoV‐2 on male reproductive function. [ABSTRACT FROM AUTHOR]

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Background: Despite the multifactorial nature of Alzheimer's disease (AD), research has primarily targeted amyloid‐beta and tau; other approaches are needed. Fosgonimeton, a small‐molecule positive modulator of the hepatocyte growth factor (HGF)/MET system, was evaluated in a randomized, double‐blind, placebo‐controlled, 6‐month, exploratory phase 2 trial (ACT‐AD; NCT04491006)a and an open‐label extension trial (NCT04886063)a. Method: To evaluate fosgonimeton in participants with mild‐to‐moderate AD, changes from baseline (CFB) in plasma biomarkers were compared with placebo in post hoc analyses. Multifactorial correlations were assessed against the global statistical test (GST), a composite score of cognition (ADAS‐Cog11) and activities of daily living (ADCS‐ADL23) assessments. Blood samples from baseline (n = 59‐61) and week 26 were assessed for biomarkers of neurodegeneration (NfL), neuroinflammation (GFAP; YKL‐40), and proteinopathy (Aβ42/40 ratio; p‐Tau181). Result: Baseline biomarker levels were similar between treatments. An ANOVA, including baseline levels, yielded a statistically significant CFB in NfL (−6.49 pg/mL; SE, 2.79; p = 0.0241) and numerical improvements in GFAP (−35.17 pg/mL; SE, 30.0; p = 0.2469), YKL‐40 (−47.37 ng/L; SE, 27.5; p = 0.0916), Aβ42/40 ratio (0.006; SE, 0.0035; p = 0.0938), and p‐Tau181 (−0.67 pg/mL; SE 0.60; p = 0.2715) were observed in fosgonimeton‐treated participants versus placebo, each without background therapy. APOE4 genotype, baseline Mini‐Mental State Examination score, sex, or age did not affect results. Additional biomarker and correlation analyses are being conducted. The potential association of biomarkers with clinical outcomes is supported by the CFB relative to GST, which significantly correlated with changes in NfL (r = 0.40; p = 0.0023) and GFAP (r = 0.35; p = 0.0408). Conclusion: In this first randomized, placebo‐controlled, 6‐month trial of fosgonimeton, a statistically significant reduction in NfL and numerical improvements in GFAP, YKL‐40, Aβ42/40, and p‐Tau181 plasma concentrations were observed, suggesting a multimodal neuroprotective mechanism of action of fosgonimeton and potential to impact AD‐specific proteinopathies. The significant correlation of NfL and GFAP reduction with the composite endpoint further supports potential clinical relevance. aThe ACT‐AD trial and open‐label extension thereof are supported by a grant from the National Institute on Aging of the National Institutes of Health (award number R01AG06268). The information presented herein is solely the responsibility of Athira and does not necessarily represent the official views of the National Institutes of Health. [ABSTRACT FROM AUTHOR]

Background: Frontotemporal dementia (FTD) is a neurodegenerative disorder marked by loss of neurons in the frontal and temporal lobes, leading to cognitive and behavioral changes. Common pathological features include neuroinflammation and intracellular inclusions of TDP‐43, which are found in approximately 50% of people with FTD. Positive modulation of the hepatocyte growth factor (HGF)/MET system has been shown to protect against several drivers of neurodegeneration and may represent a therapeutic strategy for FTD. Here, we assess the effects of ATH‐1105, a small molecule positive modulator of HGF/MET, in preclinical models that capture components of FTD, including neurodegeneration, inflammation, cognitive impairment, and TDP‐43 pathology. Method: To evaluate the neurotrophic effects of ATH‐1105, neurite length and synaptic count were measured in rat hippocampal neurons after treatment with ATH‐1105. The neuroprotective effects of ATH‐1105 were assessed in rat cortical neurons subjected to neurotoxic insults including 1‐methyl‐4‐phenylpryidinium, glutamate, lipopolysaccharide (LPS), or hydrogen peroxide. Anti‐inflammatory effects of ATH‐1105 were evaluated by measuring secreted proinflammatory cytokines in LPS‐stimulated THP‐1 differentiated macrophages. To assess pro‐cognitive effects after neuroinflammatory insult, adult mice received a single intraperitoneal injection of LPS followed by daily doses of ATH‐1105 for 14 days. Cognitive performance was assessed in the T‐maze spontaneous alternation task. Finally, Prp‐TDP43A315T mice, a model of ALS/FTD, were given daily oral treatment with 20 mg/kg ATH‐1105 or vehicle for two months, starting from one month of age. Plasma was evaluated for levels of proinflammatory cytokines and neurofilament light chain. At study termination, TDP‐43 inclusions in the sciatic nerve were measured by immunohistochemistry. Result: Treatment with ATH‐1105 increased neurite outgrowth and synaptic count in primary hippocampal neurons and protected against all cytotoxic insults in primary cortical neurons. ATH‐1105 mitigated cytokine release in LPS‐stimulated THP‐1 macrophages and attenuated LPS‐induced cognitive impairment in vivo. In TDP‐43A315T mice, treatment with ATH‐1105 reduced plasma biomarkers of inflammation and neurodegeneration. Additionally, after two months of treatment, ATH‐1105 reduced intra‐axonal TDP‐43 inclusions in the sciatic nerve. Conclusion: The data presented provide preliminary evidence that ATH‐1105 is protective against several pathological mechanisms common to FTD, including TDP‐43 protein pathology, and support its continued evaluation as a therapeutic for FTD. [ABSTRACT FROM AUTHOR]

Background: Male infertility represents a complex clinical condition requiring an accurate multilevel assessment, in which machine learning technology, combining large data series in non‐linear and highly interactive ways, could be innovatively applied. Methods: A longitudinal, observational, retrospective, big data study was carried out, applying for the first time the ML in the context of male infertility. A large database including all semen samples collected between 2010 and 2016 was generated, together with blood biochemical examinations, environmental temperature and air pollutants exposure. First, the database was analysed with principal component analysis and multivariable linear regression analyses. Second, classification analyses were performed, in which patients were a priori classified according to semen parameters. Third, machine learning algorithms were applied in a training phase (80% of the entire database) and in a tuning phase (20% of the data set). Finally, conventional statistical analyses were applied considering semen parameters and those other variables extracted during machine learning. Results: The final database included 4239 patients, aggregating semen analyses, blood and environmental parameters. Classification analyses were able to recognize oligozoospermic, teratozoospermic, asthenozoospermic and patients with altered semen parameters (0.58 accuracy, 0.58 sensitivity and 0.57 specificity). Machine learning algorithms detected three haematological variables, that is lymphocytes number, erythrocyte distribution and mean globular volume, significantly related to semen parameters (0.69 accuracy, 0.78 sensitivity and 0.41 specificity). Conclusion: This is the first machine learning application to male fertility, detecting potential mathematical algorithms able to describe patients' semen characteristics changes. In this setting, a possible hidden link between testicular and haematopoietic tissues was suggested, according to their similar proliferative properties. [ABSTRACT FROM AUTHOR]

Exon skipping is an effective strategy for the treatment of many Duchenne Muscular Dystrophy (DMD) mutations. Natural exon skipping observed in several DMD cases can help in identifying novel therapeutic tools. Here, we show a DMD study case where the lack of a splicing factor (Celf2a), which results in exon skipping and dystrophin rescue, is due to a maternally inherited trans‐generational epigenetic silencing. We found that the study case and his mother express a repressive long non‐coding RNA, DUXAP8, whose presence correlates with silencing of the Celf2a coding region. We also demonstrate that DUXAP8 expression is lost upon cell reprogramming and that, upon induction of iPSCs into myoblasts, Celf2a expression is recovered leading to the loss of exon skipping and loss of dystrophin synthesis. Finally, CRISPR/Cas9 inactivation of the splicing factor Celf2a was proven to ameliorate the pathological state in other DMD backgrounds establishing Celf2a ablation or inactivation as a novel therapeutic approach for the treatment of Duchenne Muscular Dystrophy. Synopsis: The study shows that the inhibition of Celf2a splicing factor isoform is able to partially restore dystrophin production in a subgroup of patients affected by Duchenne Muscular Dystrophy (DMD). Moreover, Celf2a expression is epigenetically regulated and this regulation is mediated by a lncRNA. Partial dystrophin restoration in a DMDΔ44 genetic background was achieved by the depletion of the Celf2a splicing factor isoform.Celf2a restoration was obtained by reprogramming patient fibroblasts into iPSCs.Celf2a silencing, in the case study analysed, is due to a transgenerationally inherited epigenetic regulation.Celf2a regulation is mediated by the lncRNA DUXAP8. [ABSTRACT FROM AUTHOR]

The partitioning of different grain‐size classes in gravity flow deposits is one of the key characteristics used to infer depositional processes. Turbidites have relatively clean sandstones with most of their clay deposited as part of a mudstone cap or as a distal mudstone layer, whereas sand‐bearing debrites commonly comprise mixtures of sand grains and interstitial clay; hybrid event beds develop alternations of clean and dirty (clay‐rich) sandstones in varying proportions. Analysis of co‐genetic mudstone caps in terms of thickness and composition is a novel approach that can provide new insight into gravity flow depositional processes. Bed thickness data from the ponded Castagnola system show that turbidites contain more clay overall than do hybrid event beds. The Castagnola system is characterized by deposits of two very different petrographic types. Thanks to this duality, analyses of sandstone and mudstone composition allow inference of which proportion of the clay in each of the deposit types was acquired en route. In combination with standard sedimentological observations the new data allow insight into the likely characteristics of their parent flows. Clean turbidites were deposited by lower concentration, long duration, erosive, muddy turbidity currents which were more efficient at fractionating clay particles away from their basal layer. Hybrid event beds were deposited by shorter duration, higher‐concentration, less‐erosive sandier flows which were less efficient at clay fractionation. The results are consistent with data from other turbidite systems (for example, Marnoso‐arenacea). The approach represents a new method to infer the controls on the degree of clay partitioning in gravity flow deposits. [ABSTRACT FROM AUTHOR]

Guanine‐quadruplexes (G4) included in RNA molecules exert several functions in controlling gene expression at post‐transcriptional level; however, the molecular mechanisms of G4‐mediated regulation are still poorly understood. Here, we describe a regulatory circuitry operating in the early phases of murine muscle differentiation in which a long non‐coding RNA (SMaRT) base pairs with a G4‐containing mRNA (Mlx‐γ) and represses its translation by counteracting the activity of the DHX36 RNA helicase. The time‐restricted, specific effect of lnc‐SMaRT on the translation of Mlx‐γ isoform modulates the general subcellular localization of total MLX proteins, impacting on their transcriptional output and promoting proper myogenesis and mature myotube formation. Therefore, the circuitry made of lnc‐SMaRT, Mlx‐γ, and DHX36 not only plays an important role in the control of myogenesis but also unravels a molecular mechanism where G4 structures and G4 unwinding activities are regulated in living cells. Synopsis: This study shows that muscle‐specific lnc‐SMaRT regulates early myogenesis. By base‐pairing to the G4 region present in the Mlx‐γ mRNA, lnc‐SMaRT controls its translation in an antagonistic manner to the RNA helicase DHX36. The Mlx‐γ mRNA, encoding a myogenic regulator, contains a G4 region and requires the DHX36 helicase for translation.lnc‐SMaRT prevents Mlx‐γ translation by base pairing to the G4 region and antagonizing DHX36 function.lnc‐SMaRT mediated regulation of Mlx‐γ modulates the subcellular localization of other MLX protein isoforms, thereby affecting their transcriptional activity in myogenesis. [ABSTRACT FROM AUTHOR]

Background: The paternal role in embryogenesis is much more than providing a haploid genome. The spermatozoa have crucial roles related to embryogenesis' epigenetic regulation, fusion of gametes, and cleavage, which may influence intracytoplasmic sperm injection outcomes. Objectives: To study whether paternal age, length of ejaculatory abstinence and semen parameters influence the outcomes of intracytoplasmic sperm injection in the oocyte recipients from egg‐sharing donation cycles. Materials and methods: This historical cohort study involved 427 oocyte recipient intracytoplasmic sperm injection cycles, from 321 patients undergoing egg‐sharing donation cycles from January 2015 to May 2017, in a private in vitro fertilization center. Electronic medical records of donors and recipients intracytoplasmic sperm injection cycles were reviewed. The impact of male age, length of ejaculatory abstinence, and semen parameters on recipients' intracytoplasmic sperm injection outcomes were investigated using general mixed models. Implantation, pregnancy, and live birth rates were the primary outcome measures. Results: Paternal age negatively affected fertilization, day 3 top‐quality embryos, day 3 normal embryo cleavage speed, blastocyst formation, high‐quality blastocysts, and implantation, and was correlated with diminished pregnancy and live birth rates. Length of ejaculatory abstinence negatively influenced the rates of day 3 top‐quality embryos, normal embryo development on day 3, blastocyst development, and implantation. Sperm count positively affected the rates of fertilization, blastocyst development, and implantation. The percentage of progressive sperm motility positively affected day 3 normal embryo development rate and implantation rate. Total motile sperm count positively affected blastocyst development rate and implantation rate. Discussion and Conclusion: Additional tracking of the influence of male characteristics on intracytoplasmic sperm injection outcomes should be stimulated. Paternal age is not manageable, but reducing length of ejaculatory abstinence could be an alternative approach to improve the outcomes of intracytoplasmic sperm injection. [ABSTRACT FROM AUTHOR]

Articular cartilage injuries are a common source of joint pain and dysfunction. We hypothesized that pulsed electromagnetic fields (PEMFs) would improve growth and healing of tissue‐engineered cartilage grafts in a direction‐dependent manner. PEMF stimulation of engineered cartilage constructs was first evaluated in vitro using passaged adult canine chondrocytes embedded in an agarose hydrogel scaffold. PEMF coils oriented parallel to the articular surface induced superior repair stiffness compared to both perpendicular PEMF (p =.026) and control (p =.012). This was correlated with increased glycosaminoglycan deposition in both parallel and perpendicular PEMF orientations compared to control (p =.010 and.028, respectively). Following in vitro optimization, the potential clinical translation of PEMF was evaluated in a preliminary in vivo preclinical adult canine model. Engineered osteochondral constructs (∅ 6 mm × 6 mm thick, devitalized bone base) were cultured to maturity and implanted into focal defects created in the stifle (knee) joint. To assess expedited early repair, animals were assessed after a 3‐month recovery period, with microfracture repairs serving as an additional clinical control. In vivo, PEMF led to a greater likelihood of normal chondrocyte (odds ratio [OR]: 2.5, p =.051) and proteoglycan (OR: 5.0, p =.013) histological scores in engineered constructs. Interestingly, engineered constructs outperformed microfracture in clinical scoring, regardless of PEMF treatment (p <.05). Overall, the studies provided evidence that PEMF stimulation enhanced engineered cartilage growth and repair, demonstrating a potential low‐cost, low‐risk, noninvasive treatment modality for expediting early cartilage repair. [ABSTRACT FROM AUTHOR]

Materials with giant spin splitting are desired for spintronic applications. The fabrications of spintronic devices from half metals with one spin direction are often hampered, however, by stray magnetic fields, domain walls, short spin coherence times, scattering on magnetic atoms or magnetically active interfaces, and other characteristics that come along with the magnetism. The surfaces of topological insulators, or Dirac/Weyl semimetals, could be an alternative, but production of high‐quality thin films without the presence of the bulk states at the Fermi energy remains very challenging. Here, by utilizing angle‐resolved photoemission spectroscopy, a record‐high Dresselhaus spin–orbit splitting of the bulk state in the nonmagnetic IrBiSe is found. The band structure calculations indicate that the splitting band is fully spin‐polarized with 3D chiral spin texture. As a source of spin‐polarized electrons, lightly doped IrBiSe is expected to generate electric‐field‐controlled spin‐polarized currents, free from back scattering, and could host triplet and Fulde–Ferrel–Larkin–Ovchinnikov (FFLO) superconductivity. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Geophysical Research. Solid Earth is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

An academic, anatomist, and Lombrosian psychiatrist active at the University of Parma in Italy at the end of the 19th century, Lorenzo Tenchini produced ceroplastic‐like masks that are unique in the anatomical Western context. These were prepared from 1885 to 1893 with the aim of 'cataloguing' the behaviour of prison inmates and psychiatric patients based on their facial surface anatomy. Due to the lack of any reference to the procedure used to prepare the masks, studies were undertaken by our group using X‐ray scans, infrared spectroscopy, bioptic sampling, and microscopy analysis of the mask constituents. Results showed that the masks were stratified structures including plaster, cotton gauze/human epidermis, and wax, leading to a fabrication procedure reminiscent of 'additive layer manufacturing'. Differences in the depths of these layers were observed in relation to the facial contours, suggesting an attempt to reproduce, at least partially, the three‐dimensional features of the facial soft tissues. We conclude the Tenchini masks are the first historical antecedent of the experimental method for face reconstruction used in the early 2000s to test the feasibility of transferring a complete strip of face and scalp from a deceased donor to a living recipient, in preparation for a complete face transplant. In addition, the layering procedure adopted conceptually mimics that developed only in the late 20th century for computer‐aided rapid prototyping, and recently applied to bioengineering with biomaterials for a number of human structures including parts of the skull and face. Finally, the masks are a relevant example of mixed ceroplastic‐cutaneous preparations in the history of anatomical research for clinical purposes. [ABSTRACT FROM AUTHOR]

Low‐energy low‐frequency pulsed electromagnetic fields (PEMFs) exert several protective effects, such as the regulation of kinases, transcription factors as well as cell viability in both central and peripheral biological systems. However, it is not clear on which bases they affect neuroprotection and the mechanism responsible is yet unknown. In this study, we have characterized in nerve growth factor‐differentiated pheochromocytoma PC12 cells injured with hypoxia: (i) the effects of PEMF exposure on cell vitality; (ii) the protective pathways activated by PEMFs to relief neuronal cell death, including adenylyl cyclase, phospholipase C, protein kinase C epsilon and delta, p38, ERK1/2, JNK1/2 mitogen‐activated protein kinases, Akt and caspase‐3; (iii) the regulation by PEMFs of prosurvival heat‐shock proteins of 70 (HSP70), cAMP response element‐binding protein (CREB), brain‐derived neurotrophic factor (BDNF), and Bcl‐2 family proteins. The results obtained in this study show a protective effect of PEMFs that are able to reduce neuronal cell death induced by hypoxia by modulating p38, HSP70, CREB, BDNF, and Bcl‐2 family proteins. Specifically, we found a rapid activation (30 min) of p38 kinase cascade, which in turns enrolles HSP70 survival chaperone molecule, resulting in a significant CREB phosphorylation increase (24 hr). In this cascade, later (48 hr), BDNF and the antiapoptotic pathway regulated by the Bcl‐2 family of proteins are recruited by PEMFs to enhance neuronal survival. This study paves the way to elucidate the mechanisms triggered by PEMFs to act as a new neuroprotective approach to treat cerebral ischemia by reducing neuronal cell death. [ABSTRACT FROM AUTHOR]

Background: Regulatory bodies recommend inconsistent ejaculatory abstinence lengths before semen analysis. The literature exploring the effect of ejaculatory abstinence length on the outcomes of intracytoplasmic sperm injection is scarce. Objective: To study the influence of ejaculatory abstinence length on semen quality and intracytoplasmic sperm injection outcomes. Materials and methods: This prospective cohort study included 818 patients undergoing conventional semen analysis from October 2015 to October 2016, in a private university‐affiliated IVF centre. Generalized linear models adjusted for potential confounders were used to investigate the associations between ejaculatory abstinence length and seminal parameters and intracytoplasmic sperm injection outcomes. Results: Increasing ejaculatory abstinence length was positively correlated with semen volume, sperm concentration, total sperm count, total motile sperm count and sperm DNA fragmentation index. Significant inverse correlations were observed between ejaculatory abstinence length and fertilization rate, blastocyst formation rate, implantation rate and pregnancy rate. A discriminant analysis showed a mean ejaculatory abstinence length in the positive pregnancy group of 3.14 ± 1.64 days and 4.83 ± 3.66 days in the negative pregnancy group. A cut‐off point was established halfway between ejaculatory abstinence length averages, at 4 days. The ejaculatory abstinence ≤4 days group showed significant lower semen volume, sperm concentration, total sperm count and total motile sperm count compared to ejaculatory abstinence > 4 days group. The ejaculatory abstinence ≤ 4 days group showed significant lower sperm DNA fragmentation index, and higher rates of fertilization, high‐quality embryos on day 3, blastocyst development, implantation and pregnancy compared to ejaculatory abstinence > 4 days group. The implantation rate was significantly higher and the pregnancy rate tended to be higher with one day of ejaculatory abstinence, compared to 2–4 days of ejaculatory abstinence. Conclusions: Ejaculatory abstinence periods of >4 days have a detrimental effect on sperm DNA and intracytoplasmic sperm injection outcomes. One day of ejaculatory abstinence significantly improves implantation rate and tends to increase pregnancy rate, compared to 2, 3 and 4 days of ejaculatory abstinence. [ABSTRACT FROM AUTHOR]

Low-intensity pulsed ultrasound (LIPUS) as an adjuvant therapy in in vitro and in vivo bone engineering has proven to be extremely useful. The present study aimed at investigating the effect of 30 mW/cm² LIPUS stimulation on commercially available human mesenchymal stem cells (hMSCs) cultured in basal or osteogenic medium at different experimental time points (7, 14, 21 days). The hypothesis was that LIPUS would improve the osteogenic differentiation of hMSC and guarantying the maintenance of osteogenic committed fraction, as demonstrated by cell vitality and proteomic analysis. LIPUS stimulation (a) regulated the balance between osteoblast commitment and differentiation by specific networks (activations of RhoA/ROCK signaling and upregulation of Ribosome constituent/Protein metabolic process, Glycolysis/Gluconeogenesis, RNA metabolic process/Splicing and Tubulins); (b) allowed the maintenance of a few percentage of osteoblast precursors (21 days CD73+/CD90+: 6%; OCT-3/4+/NANOG+/SOX2+: 10%); (c) induced the activation of osteogenic specific pathways shown by gene expression (early: ALPL, COL1A1, late: RUNX2, BGLAP, MAPK1/6) and related protein release (COL1a1, OPN, OC), in particular in the presence of osteogenic soluble factors able to mimic bone microenvironment. To summarize, LIPUS might be able to improve the osteogenic commitment of hMSCs in vitro, and, at the same time, enhance their osteogenic differentiation. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the role of metabolic parameters analyzed at baseline and at interim FDG-PET in predicting disease outcome in unresectable MPM patients receiving pemetrexed-based chemotherapy. A consecutive series of MPM patients treated between February 2004 and July 2013 with first-line pemetrexed-based chemotherapy, and evaluated by FDG-PET and CT scan at baseline and after two cycles of chemotherapy, was reviewed. Best CT scan response was assessed according to modified RECIST criteria. Progression-free survival (PFS) and overall survival (OS) were correlated with FDG-PET parameters, such as maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG), and percentage changes in SUVmax (∆SUV) and TLG (∆TLG). Overall, 142 patients were enrolled; 77 (54%) received talc pleurodesis before chemotherapy. Baseline SUVmax and TLG showed a statistically significant correlation with PFS and OS ( P < 0.05) in both group of patients (treated and untreated with pleurodesis). In 65 patients not receiving pleurodesis, SUVmax reduction ≥25% (∆SUV ≥ 25%) and TLG reduction ≥30% (∆TLG ≥ 30%) were significantly associated with longer PFS ( P < 0.05). Patients showing both ∆SUV ≥ 25% and ∆TLG ≥ 30% responses had a significant reduction in the risk of disease progression (HR:0.31, P < 0.001) and death (HR:0.52, P = 0.044). Neither ∆SUV nor ∆TLG showed similar association with survival outcomes in patients treated with pleurodesis. Our study confirmed the prognostic role of baseline FDG-PET in a large series of MPM patients treated with first-line pemetrexed-based chemotherapy. Moreover, use of ∆SUV ≥ 25% and ∆TLG ≥ 30% as cut-off values to define early metabolic response supported the role of FDG-PET in predicting disease outcome and treatment response in patients not receiving pleurodesis. [ABSTRACT FROM AUTHOR]

In the present study, the effect of low-frequency, low-energy pulsed electromagnetic fields (PEMFs) has been investigated by using different cell lines derived from neuron-like cells and microglial cells. In particular, the primary aim was to evaluate the effect of PEMF exposure in inflammation- and hypoxia-induced injury in two different neuronal cell models, the human neuroblastoma-derived SH-SY5Y cells and rat pheochromocytoma PC12 cells and in N9 microglial cells. In neuron-like cells, live/dead and apoptosis assays were performed in hypoxia conditions from 2 to 48 h. Interestingly, PEMF exposure counteracted hypoxia damage significantly reducing cell death and apoptosis. In the same cell lines, PEMFs inhibited the activation of the hypoxia-inducible factor 1α (HIF-1α), the master transcriptional regulator of cellular response to hypoxia. The effect of PEMF exposure on reactive oxygen species (ROS) production in both neuron-like and microglial cells was investigated considering their key role in ischemic injury. PEMFs significantly decreased hypoxia-induced ROS generation in PC12, SH-SY5Y, and N9 cells after 24 or 48 h of incubation. Moreover, PEMFs were able to reduce some of the most well-known pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-8 release in N9 microglial cells stimulated with different concentrations of LPS for 24 or 48 h of incubation time. These results show a protective effect of PEMFs on hypoxia damage in neuron-like cells and an anti-inflammatory effect in microglial cells suggesting that PEMFs could represent a potential therapeutic approach in cerebral ischemic conditions. J. Cell. Physiol. 232: 1200-1208, 2017. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]