Prenatal intimate partner violence exposure predicts infant biobehavioral regulation: Moderation by the brain-derived neurotrophic factor (BDNF) gene.

The ability to regulate stress is a critical developmental milestone of early childhood that involves a set of interconnected behavioral and physiological processes and is influenced by genetic and environmental stimuli. Prenatal exposure to traumatic stress and trauma, including intimate partner violence (IPV), increases risk for offspring biobehavioral regulation problems during childhood and adolescence. Although individual differences in susceptibility to prenatal stress have been largely unexplored, a handful of studies suggest children with specific genetic characteristics are most vulnerable to prenatal stress. We evaluated the brain-derived neurotrophic factor Val66Met gene (BDNF) as a moderator of the effect of prenatal IPV exposure on infant temperamental and cortisol regulation in response to a psychosocial challenge. Ninety-nine mother-infant dyads recruited from the community were assessed when infants (51% female) were 11 to 14 months. Maternal reports of IPV during pregnancy and infant temperament were obtained, and infant saliva was collected for genotyping and to assess cortisol reactivity (before and after the Strange Situation Task). Significant genetic moderation effects were found. Among infants with the BDNF Met allele, prenatal IPV predicted worse temperamental regulation and mobilization of the cortisol response, while controlling for infant postnatal exposure to IPV, other maternal traumatic experiences, and infant sex. However, prenatal IPV exposure was not associated with temperamental or cortisol outcomes among infant carriers of the Val/Val genotype. Findings are discussed in relation to prenatal programming and biological susceptibility to stress.

'Clinical Chatter': every nurse informed.

AIMS AND OBJECTIVES: To assess the acceptability and usability of a standardised communication tool for nurses. BACKGROUND AND SIGNIFICANCE: Communication is key in health care. On a daily, if not hourly, basis, nursing staff is inundated with new information regarding tools and resources, practice changes and the work environment. However, there is currently no standardised messaging or delivery method to effectively communicate new information. Even with a plethora of communication tools such as flyers, posters, emails, unit huddles and unit meetings, there is no means to guarantee attendance to crucial information. DESIGN: Descriptive, cross-sectional online survey, implemented at a nonacademic, suburban hospital with 280 nurses. METHODS: The Clinical Chatter, an online tool developed by nursing leadership to standardise messages regarding the organisation, new tools and resources, professional development, recognition and unit updates, was delivered to each nurse on a weekly basis followed by administration of Acceptability and Usability scales. RESULTS: The Clinical Chatter tool has adequate acceptability and usability as a method of communication among nurses in a hospital organisation. Sociodemographic variables of age and years of experience had no statistically significant association with perceived acceptance and usefulness of the tool. CONCLUSION: The findings indicate that the Clinical Chatter tool can be used as a standardised communication tool to deliver key information among nurses working in a hospital organisation. Nursing leadership must establish and support a clear communication system to enhance patient care and outcomes and improve nursing job satisfaction. RELEVANCE TO CLINICAL PRACTICE: Communication is vital to advancing health care. Lack of communication among nursing has been linked to unsafe patient care: medication errors, unhealthy work environments and decreased nurse retention rates. Clinical Chatter is an effective communication tool for presentation of institutional information to nursing personnel.

Rapid identification of mRNA processing defects with a novel single-cell yeast reporter.

It has become increasingly evident that gene expression processes in eukaryotes involve communication and coordination between many complex, independent macromolecular machines. To query these processes and to explore the potential relationships between them in the budding yeast Saccharomyces cerevisiae, we designed a versatile reporter using multicolor high-throughput flow cytometry. Due to its design, this single reporter exhibits a distinctive signature for many defects in gene expression including transcription, histone modification, pre-mRNA splicing, mRNA export, nonsense-mediated decay, and mRNA degradation. Analysis of the reporter in 4967 nonessential yeast genes revealed striking phenotypic overlaps between chromatin remodeling, histone modification, and pre-mRNA splicing. Additionally, we developed a copper-inducible reporter, with which we demonstrate that 5-fluorouracil mimics the mRNA decay phenotype of cells lacking the 3'-5' exonuclease Rrp6p. Our reporter is capable of performing high-throughput, rapid, and large-scale screens to identify and characterize genetic and chemical perturbations of the major eukaryotic gene expression processes.

Histone H3K36 methylation regulates pre-mRNA splicing in Saccharomyces cerevisiae.

Co-transcriptional splicing takes place in the context of a highly dynamic chromatin architecture, yet the role of chromatin restructuring in coordinating transcription with RNA splicing has not been fully resolved. To further define the contribution of histone modifications to pre-mRNA splicing in Saccharomyces cerevisiae, we probed a library of histone point mutants using a reporter to monitor pre-mRNA splicing. We found that mutation of H3 lysine 36 (H3K36) - a residue methylated by Set2 during transcription elongation - exhibited phenotypes similar to those of pre-mRNA splicing mutants. We identified genetic interactions between genes encoding RNA splicing factors and genes encoding the H3K36 methyltransferase Set2 and the demethylase Jhd1 as well as point mutations of H3K36 that block methylation. Consistent with the genetic interactions, deletion of SET2, mutations modifying the catalytic activity of Set2 or H3K36 point mutations significantly altered expression of our reporter and reduced splicing of endogenous introns. These effects were dependent on the association of Set2 with RNA polymerase II and H3K36 dimethylation. Additionally, we found that deletion of SET2 reduces the association of the U2 and U5 snRNPs with chromatin. Thus, our study provides the first evidence that H3K36 methylation plays a role in co-transcriptional RNA splicing in yeast.

Skating crossovers on a motorized flywheel: a preliminary experimental design to test effect on speed and on crossovers.

Ice hockey requires frequent skater crossovers to execute turns. Our investigation aimed to determine the effectiveness of training crossovers on a motorized, polyethylene high-resistance flywheel. We hypothesized that high school hockey players training on the flywheel would perform as well as their peers training on ice. Participants were 23 male high-school hockey players (age 15-19 years). The study used an experimental prospective design to compare players who trained for 9 sessions on the 22-foot flywheel with players who trained for 9 sessions on a similarly sized on-ice circle. Both groups were compared with control subjects who were randomly selected from the same participant pool as those training on ice. All players were tested before and after their 3-week training regimens, and control subjects were asked to not practice crossovers between testing. Group 1 trained in a hockey training facility housing the flywheel, and group 2 trained in the ice hockey arena where testing occurred. Primary outcome measures tested in both directions were: (a) speed (time in seconds) required to skate crossovers for 3 laps of a marked face-off circle, (b) cadence of skating crossovers on the similarly sized circles, and (c) a repeat interval speed test, which measures anaerobic power. No significant changes were found between groups in on-ice testing before and after training. Among the group 1 players, 7 of 8 believed they benefited from flywheel training. Group 2 players, who trained on ice, did not improve performance significantly over group 1 players. Despite the fact that no significant on-ice changes in performance were observed in objective measures, players who trained on the flywheel subjectively reported that the flywheel is an effective cost-effective alternative to training on ice. This is a relevant finding when placed in context with limited availability of on-ice training.

Cognitive and physical impairment in spinal cord injury: A scoping review and call for new understanding.

Study Design: Scoping review.Objective: To examine potential underlying mechanisms of cognitive and physical impairment in patients with spinal cord injury and identify current research gaps.Methods: A scoping review of the literature was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews to identify primary studies that explored mechanisms of cognitive and/or physical impairment after spinal cord injury. The databases searched were PubMed/MEDLINE, EMBASE (OVID), Cumulative Index to Nursing and Allied Health Literature (CINAHL; EBSCO), Web of Science, Scopus, and PsycInfo. These databases were searched from inception through December 20, 2021.Results: Accumulating research suggests that neuroinflammation and neurodegeneration after a traumatic event may be possible mechanisms for cognitive impairment among patients with SCI. In addition, lack of physical activity due to impaired mobility is associated with an increased risk of cognitive impairment.Conclusion: While the results establish a foundation for understanding how cognitive impairment, mental health, and physical function independently affect patients with SCI, further research is warranted to understand how these factors systemically impact the patient and discover refined targets for future rehabilitation therapies. Studies should also explore potential predisposing factors for the relationship between cognitive and physical impairment among patients with SCI.

Cytokine network analysis in a community-based pediatric sample of patients with myalgic encephalomyelitis/chronic fatigue syndrome.

OBJECTIVES: Studies have demonstrated immune dysfunction in adolescents with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS); however, evidence is varied. The current study used network analysis to examine relationships between cytokines among a sample of pediatric participants with ME/CFS. METHODS: 10,119 youth aged 5-17 in the Chicagoland area were screened for ME/CFS; 111 subjects and controls were brought in for a physician examination and completed a blood draw. Youth were classified as controls (Cs, N = 43), ME/CFS (N = 23) or severe (S-ME/CFS, N = 45). Patterns of plasma cytokine networks were analyzed. RESULTS: All participant groups displayed a primary network of interconnected cytokines. In the ME/CFS group, inflammatory cytokines IL-12p70, IL-17A, and IFN-γ were connected and included in the primary membership, suggesting activation of inflammatory mechanisms. The S-ME/CFS group demonstrated a strong relationship between IL-17A and IL-23, a connection associated with chronic inflammation. The relationships of IL-6 and IL-8 in ME/CFS and S-ME/CFS participants also differed from Cs. Together, these results indicate pro-inflammatory responses in our illness populations. DISCUSSION: Our data imply biological differences between our three participant groups, with ME/CFS and S-ME/CFS participants demonstrating an inflammatory profile. Examining co-expression of cytokines may aid in the identification of a biomarker for pediatric ME/CFS.

Efficacy and satisfaction rates of oral PDE5is in the treatment of erectile dysfunction secondary to spinal cord injury: a review of literature.

CONCEPT: Decreased sexual function is a major concern of men with spinal cord injuries (SCIs). Treatment of erectile dysfunction (ED) through oral pharmacotherapies has been proven to be an effective way to address and treat this concern. OBJECTIVE: To find an efficacious and satisfactory treatment ED secondary to SCI through the compilation of studies that utilized the International Index of Erectile Function (IIEF) when testing phosphodiesterase V inhibitors (PDE5i). METHOD: Ten articles, which used the IIEF to study satisfaction and/or efficacy of PDE5is sildenafil, tadalafil, and vardenafil in the treatment of ED were reviewed and analyzed. Through the use of a self-made grading scale the value of each article was determined for this research. RESULTS: Sildenafil, tadalafil, and vardenafil all have been proven to be effective in treating ED in men with SCI. While sildenafil is the most thoroughly studied ED treatment for patients with SCI, tadalafil has a longer time duration effectiveness, which allows for more spontaneity in the sexual experience. Minimal adverse effects have been noted in patients with SCI using these medications; headache, flushing, and mild hypotension are the most common. In articles that study satisfaction, patients show great improvement over baseline with the use of these medications. CONCLUSION: Although there is a need for further research on the safety in long-term use of tadalafil and vardenafil, comparative studies done on all three medications show no statistically significant difference in effectiveness or satisfaction. New medications and treatment options, such as avanafil, are being studied in hope of continued improvement of sexual function in men with SCI.

Increased HDAC in association with decreased plasma cortisol in older adults with chronic fatigue syndrome.

Hypocortisolism is a frequent finding in individuals with chronic fatigue syndrome (CFS) with other research findings implying potential dysregulation of glucocorticoid signaling. Glucocorticoid signaling is under the influence of several pathways, several of which are of interest in the study of CFS. Oxidative stress and decreased antioxidant capacity are known to disrupt the hypothalamic-pituitary-adrenal (HPA) axis (Epel et al., 2004) and the presence of histone deacetylases (HDAC) could also impact glucocorticoid signaling. The intent of this pilot study was to investigate the relationship among oxidative stress elements, select HDAC's (2/3) and glucocorticoid receptor signaling in an elderly sample with CFS. Findings suggest increased histone deacetylase activity, lower total antioxidant power, in the context of decreased plasma cortisol and increased plasma dehydroepiandrosterone concomitant with decreased expression of the encoding gene for the glucocorticoid receptor. These findings support the presence of HPA axis dysregulation in elderly individuals with CFS.

The effect of residual osteomyelitis at the resection margin in patients with surgically treated diabetic foot infection.

The appropriate antibiotic treatment of surgically resected diabetic foot osteomyelitis is controversial. We conducted a retrospective cohort study to evaluate the prognostic impact of residual osteomyelitis at the surgical margin of surgically resected diabetic foot osteomyelitis, and to assess the effectiveness of postoperative antibiotic therapy for residual osteomyelitis after surgical resection of infected bone. Of the 111 patients included in the study, 39 (35.14%) had pathologically confirmed margins positive for residual osteomyelitis. The median total duration of antibiotic treatment was 19 (range 10-134) days in patients with positive margins, whereas it was 14 (range 2-63) days in those with negative margins (P = .01). No statistically significant difference (P = .695) was found in the primary outcome of definite failure, defined as pathologically or microbiologically confirmed infection relapse at the proximal amputation site, between 3 (7.69%) of 39 patients with positive margins and 4 (5.56%) of 47 patients with negative margins. A statistically significant difference (P = .001) in the secondary outcome, definite treatment failure, or the need for more proximal amputation was found between 17 (43.59%) of 39 patients with positive margins and 11 (15.28%) of 72 patients with negative margins. Residual osteomyelitis at the pathologic margin was associated with a higher rate of treatment failure, despite the longer duration of antibiotic therapy.

Fisetin for COVID-19 in skilled nursing facilities: Senolytic trials in the COVID era.

The burden of senescent cells (SnCs), which do not divide but are metabolically active and resistant to death by apoptosis, is increased in older adults and those with chronic diseases. These individuals are also at the greatest risk for morbidity and mortality from SARS-CoV-2 infection. SARS-CoV-2 complications include cytokine storm and multiorgan failure mediated by the same factors as often produced by SnCs through their senescence-associated secretory phenotype (SASP). The SASP can be amplified by infection-related pathogen-associated molecular profile factors. Senolytic agents, such as Fisetin, selectively eliminate SnCs and delay, prevent, or alleviate multiple disorders in aged experimental animals and animal models of human chronic diseases, including obesity, diabetes, and respiratory diseases. Senolytics are now in clinical trials for multiple conditions linked to SnCs, including frailty; obesity/diabetes; osteoporosis; and cardiovascular, kidney, and lung diseases, which are also risk factors for SARS-CoV-2 morbidity and mortality. A clinical trial is underway to test if senolytics decrease SARS-CoV-2 progression and morbidity in hospitalized older adults. We describe here a National Institutes of Health-funded, multicenter, placebo-controlled clinical trial of Fisetin for older adult skilled nursing facility (SNF) residents who have been, or become, SARS-CoV-2 rtPCR-positive, including the rationale for targeting fundamental aging mechanisms in such patients. We consider logistic challenges of conducting trials in long-term care settings in the SARS-CoV-2 era, including restricted access, consent procedures, methods for obtaining biospecimens and clinical data, staffing, investigational product administration issues, and potential solutions for these challenges. We propose developing a national network of SNFs engaged in interventional clinical trials.

Skate blade neck lacerations: a survey and case follow-up.

OBJECTIVE: To learn about neck lacerations caused by skate blades in hockey. DESIGN: A retrospective Web-based survey and follow-up of registered USA Hockey players. SETTING: Three hundred twenty-eight thousand eight hundred twenty-one of 457 038 registered USA Hockey players with a current e-mail address were contacted and invited to participate in the survey. PARTICIPANTS: Of 26 589 players (5.8% of all USA registered players) who responded to the survey, 247 were excluded due to incomplete data. Of 26 342 surveys analyzed, 23 199 respondents were men (88%), 3015 women (11.4%), and 128 (0.5%) did not designate gender. INTERVENTION: An original survey instrument was developed, formatted, and linked to a Mayo Clinic Web site. MAIN OUTCOME MEASURES: Neck lacerations from a skate blade, including mechanism, severity, treatment required, and the type of neck protector worn. RESULTS: Of the 26 342 respondents, 11 935 (45.4%) currently wear neck protection and 485 (1.8%) have sustained a neck laceration. When the laceration occurred, 132 of the players (27%) were wearing neck protection. Interviews with 33 injured players established that lacerations were superficial: 20 (61%) required bandaging only, 11 were sutured, and 2 were glued. CONCLUSION: Based on this survey, the currently available neck laceration protectors do not eliminate the risk of a neck laceration from a skate blade.

The associations between basal salivary cortisol and illness symptomatology in chronic fatigue syndrome.

Hypocortisolism has been reported in chronic fatigue syndrome (CFS), with the significance of this finding to disease etiology unclear. This study examined cortisol levels and their relationships with symptoms in a group of 108 individuals with CFS. CFS symptoms examined included fatigue, pain, sleep difficulties, neurocognitive functioning, and psychiatric status. Alterations in cortisol levels were examined by calculation of mean daily cortisol, while temporal variation in cortisol function was examined by means of a regression slope. Additionally, deviation from expected cortisol diurnal pattern was determined via clinical judgment. Results indicated that fatigue and pain were associated with salivary cortisol levels. In particular, variance from the expected pattern of cortisol was associated with increased levels of fatigue. The implications of these findings are discussed.

Ephedra use in a select group of adolescent athletes.

Ephedra-containing dietary supplements are consumed to improve sports performace, but may carry risks of cardiac and neurological adverse events. Little is known of their use by young athletes. Our aim was to determine the prevalence and patterns of ephedra use among high school athletes. An anonymous survey was performed in Rochester, Minnesota on high school athletes who participated in fall sports during 2003-04. Parental consent was obtained for athletes under age 18 years. Surveys were distributed at preparticipation examinations and in- school survey stations. The response rate to the survey was 68.2%, or 311 respondents out of a possible 456 with consent (or 26% of all 1197 athletes eligible prior to the consent process). Seven of 311 (2.3%) respondents used dietary supplements containing ephedra. Only one of seven users (14.3%) knew that the supplements they used contained ephedra. Ephedra use was more common in boys (five) than girls (two). Ephedra use was only found in 17 and 18-year-olds. The most common sports among ephedra users were football, track and field, and weightlifting. This study suggests that Ephedra use was infrequent among the young athletes in this population. However, ephedra users were generally unaware that the dietary supplements they consumed contained ephedra. Users were more likely to participate in football, track and field, and weightlifting. Ephedra users were likely to obtain supplements from their peers, and were largely uninformed of the content of their supplements. Key PointsEphedra is an herbal stimulant used as an ergogenic aide.Adolescent ephedra users most commonly obtain it from their friends.Adolescent athletes are likely to take ephedra unknowningly.

Central fatigue in multiple sclerosis: a review of the literature.

CONCEPT: Fatigue is a major concern for patients with multiple sclerosis (MS). A clear definition of MS-related fatigue is a prerequisite for appropriate instruments for fatigue assessment. In turn, accurate assessment of fatigue in MS will enhance exploration of plausible mechanisms underlying this common and distressing symptom. Content/Objectives: To provide an integrative review of the current literature on theoretical models used to study fatigue in MS, instruments used to assess fatigue and other factors that impact fatigue during the various phases of MS. DATA SOURCES: PUBMED, OVID, Ovid Health Star, Ovid MEDINE, CINAHL, Health and Psychosocial Instruments (HaPI), and PsycINFO. Seventeen articles fit the inclusion criteria and were included in the review. RESULTS: Definitions of MS-related fatigue are reviewed. Several studies found a link with neurotransmitter dysfunction, circadian rhythm, and the timing of fatigue. Central fatigue in MS is associated with neurotransmitters disruptions as well as circadian rhythm disorders, but the evidence is not strong. Perceptions of fatigue or fatigability may arise as either a primary or secondary manifestation of disease. Based on findings from the literature review, a theoretical model of fatigue in MS is proposed. CONCLUSION: Future research on MS-related fatigue may consider a longitudinal design with a carefully selected self-report instrument to advance understanding of the underlying pathological mechanisms.

The 'yips' in golf: a continuum between a focal dystonia and choking.

The definition of the 'yips' has evolved over time. It is defined as a motor phenomenon of involuntary movements affecting golfers. In this paper, we have extended the definition to encompass a continuum from the neurologic disorder of dystonia to the psychologic disorder of choking. In many golfers, the pathophysiology of the 'yips' is believed to be an acquired deterioration in the function of motor pathways (e.g. those involving the basal ganglia) which are exacerbated when a threshold of high stress and physiologic arousal is exceeded. In other golfers, the 'yips' seems to result from severe performance anxiety. Physically, the 'yips' is manifested by symptoms of jerks, tremors or freezing in the hands and forearms. These symptoms can result in: (i) a poor quality of golf performance (adds 4.9 strokes per 18 holes); (ii) prompt use of alcohol and beta-blockers; and (iii) contribute to attrition in golf. Golfers with the 'yips' average 75 rounds per year, although many 'yips'-affected golfers decrease their playing time or quit to avoid exposure to this embarrassing problem. While more investigation is needed to determine the cause of the 'yips', this review article summarises and organises the available research. A small study included in this paper describes the 'yips' phenomenon from the subjective experience of 'yips'-affected golfers. The subjective experience (n = 72) provides preliminary support for the hypothesis suggesting that the 'yips' is on a continuum. Based on the subjective definitions of 72 'yips'-affected golfers, the 'yips' was differentiated into type I (dystonia) and type II (choking). A theoretical model provides a guide for future research on golfers with either type I or type II 'yips'.

Psychological stress and cytokine production in multiple sclerosis: correlation with disease symptomatology.

OBJECTIVE: Psychological variables such as perceived stress appear to play a role in symptom onset or disease exacerbation in multiple sclerosis (MS). The authors sought to determine if perceived stress is indeed associated with the expression of pro-inflammatory cytokines and disease symptoms in individuals with MS. To do so, the authors examined the relationships among disease symptomatology, perceived stress, and cytokine production from peripheral blood mononuclear cells in 42 outpatients with MS and 36 normative controls. METHOD: The authors drew peripheral blood from all subjects prior to the completion of a series of psychological instruments. The authors measured stress using the Perceived Stress scale and negative mood with the Profile of Mood States. Disease symptoms were measured using the Multiple Sclerosis Symptom Checklist. Cytokine production was induced separately by lipopolysaccharide and a combination of phytohemagglutinin and phorbol-12-myristate-13-acetate. RESULTS: In MS subjects, the induced production of interleukin (IL)-6 and IL-10 positively correlated with psychological stress, mood disturbance, and disease symptomatology. In contrast, psychological stress in control subjects significantly correlated with level of tumor necrosis factor-alpha (TNF-α), and mood disturbance correlated with levels of TNF-α and interferon-gamma. As well, compared to controls, MS subjects exhibited a significant fourfold increase in the production of IL-12. CONCLUSION: There is, in those with MS, a pattern of IL-6 and IL-10 production that correlates significantly with perceived stress and disease symptomatology.