A Biodegradable "One-For-All" Nanoparticle for Multimodality Imaging and Enhanced Photothermal Treatment of Breast Cancer.

Silver sulfide nanoparticles (Ag2S-NP) hold promise for various optical-based biomedical applications, such as near-infrared fluorescence (NIRF) imaging, photoacoustics (PA), and photothermal therapy (PTT). However, their NIR absorbance is relatively low, and previous formulations are synthesized using toxic precursors under harsh conditions and are not effectively cleared due to their large size. Herein, sub-5 nm Ag2S-NP are synthesized and encapsulated in biodegradable, polymeric nanoparticles (AgPCPP). All syntheses are conducted using biocompatible, aqueous reagents under ambient conditions. The encapsulation of Ag2S-NP in polymeric nanospheres greatly increases their NIR absorbance, resulting in enhanced optical imaging and PTT effects. AgPCPP nanoparticles exhibit potent contrast properties suitable for PA and NIRF imaging, as well as for computed tomography (CT). Furthermore, AgPCPP nanoparticles readily improve the conspicuity of breast tumors in vivo. Under NIR laser irradiation, AgPCPP nanoparticles significantly reduce breast tumor growth, leading to prolonged survival compared to free Ag2S-NP. Over time, AgPCPP retention in tissues gradually decreases, without any signs of acute toxicity, providing strong evidence of their safety and biodegradability. Therefore, AgPCPP may serve as a "one-for-all" theranostic agent that degrades into small components for excretion after fulfilling diagnostic and therapeutic tasks, offering good prospects for clinical translation.

Hounsfield Unit-Calculated Bone Mineral Density Loss Following Combat-Related Lower Extremity Amputations.

BACKGROUND: After combat-related lower extremity amputations, patients rapidly lose bone mineral density (BMD). As serial dual x-ray absorptiometry (DXA) scans are rarely performed in this setting, it is difficult to determine the timeline for bone loss and recovery or the role of interventions. However, a strong correlation has been demonstrated between DXA BMD and computed tomography (CT) signal attenuation. We sought to leverage multiple CT scans obtained after trauma to develop a predictive model for BMD after combat-related lower extremity amputations. METHODS: We reviewed amputations performed within the United States military between 2003 and 2016 in patients with multiple CT scans. We collected pertinent clinical information, including amputation level(s), complications, and time to weight-bearing. The primary outcome measure was the development of low BMD, estimated in Hounsfield units (HU) from CT scans with use of a previously validated method. One hundred and twenty-eight patients with 613 femoral neck CT scans were available for analysis. A least absolute shrinkage and selection operator (LASSO) multiple logistic regression analysis was applied to determine the effects of modifiable and non-modifiable variables on BMD. A random-effects model was applied to determine which factors were most predictive of low BMD and to quantify their effects. RESULTS: Both amputated and non-amputated extremities demonstrated substantial BMD loss, which stabilized approximately 3 years after the injury. Loss of BMD followed a logarithmic pattern, stabilizing after 1,000 days. On average, amputated limbs lost approximately 100 HU of BMD after 1,000 days. Other factors identified by the mixed-effects model included nonambulatory status (-33.5 HU), age at injury (-3.4 HU per year), surgical complications delaying weight-bearing (-21.3 HU), transtibial amputation (20.9 HU), and active vitamin-D treatment (-19.7 HU). CONCLUSIONS: Patients with combat-related lower extremity amputations experience an initially rapid decline in BMD in both intact and amputated limbs as a result of both modifiable and non-modifiable influences, including time to walking, amputation level, surgical complications, and age. The paradoxical association of vitamin-D supplementation with lower HU likely reflects this treatment being assigned to patients with low BMD. This model may assist with clinical decision-making prior to performing lower extremity amputation and also may assist providers with postoperative decision-making to optimize management for prophylaxis against osteoporosis. LEVEL OF EVIDENCE: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Transcranial Magnetic Stimulation of the Dorsolateral Prefrontal Cortex Increases Posterior Theta Rhythm and Reduces Latency of Motor Imagery.

Experiments show activation of the left dorsolateral prefrontal cortex (DLPFC) in motor imagery (MI) tasks, but its functional role requires further investigation. Here, we address this issue by applying repetitive transcranial magnetic stimulation (rTMS) to the left DLPFC and evaluating its effect on brain activity and the latency of MI response. This is a randomized, sham-controlled EEG study. Participants were randomly assigned to receive sham (15 subjects) or real high-frequency rTMS (15 subjects). We performed EEG sensor-level, source-level, and connectivity analyses to evaluate the rTMS effects. We revealed that excitatory stimulation of the left DLPFC increases theta-band power in the right precuneus (PrecuneusR) via the functional connectivity between them. The precuneus theta-band power negatively correlates with the latency of the MI response, so the rTMS speeds up the responses in 50% of participants. We suppose that posterior theta-band power reflects attention modulation of sensory processing; therefore, high power may indicate attentive processing and cause faster responses.

Metal-Based Anticancer Complexes and p53: How Much Do We Know?

P53 plays a key role in protecting the human genome from DNA-related mutations; however, it is one of the most frequently mutated genes in cancer. The P53 family members p63 and p73 were also shown to play important roles in cancer development and progression. Currently, there are various organic molecules from different structural classes of compounds that could reactivate the function of wild-type p53, degrade or inhibit mutant p53, etc. It was shown that: (1) the function of the wild-type p53 protein was dependent on the presence of Zn atoms, and (2) Zn supplementation restored the altered conformation of the mutant p53 protein. This prompted us to question whether the dependence of p53 on Zn and other metals might be used as a cancer vulnerability. This review article focuses on the role of different metals in the structure and function of p53, as well as discusses the effects of metal complexes based on Zn, Cu, Fe, Ru, Au, Ag, Pd, Pt, Ir, V, Mo, Bi and Sn on the p53 protein and p53-associated signaling.

Safety and efficacy of vitamin B in cancer treatments: A systematic review.

BACKGROUND: With rising rates of complementary and alternative medicine use, the exploration of complementary and alternative medicine integration into oncology treatments is becoming increasingly prevalent. Vitamin B compounds including B1, B2, B3, B5, B6, B9, and B12, have all been proposed as potentially beneficial in cancer prevention and treatment as well as side effect management; however, many studies contain contradicting evidence regarding the utility of B vitamins within oncology. Thus, the aim of this study was to evaluate the safety and efficacy of Vitamin B supplementation in the oncology setting. DESIGN: A systematic review was conducted following The Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Scoping Reviews guidelines, using pre-specified search terms in PubMed to include randomized control trials, clinical trials, and case studies. Two reviewers independently reviewed titles, abstracts, and full-text articles for inclusion, with a third reviewer resolving conflicts, before the included articles underwent data extraction and quality appraisal. Data extraction was conducted through COVIDENCE, which was used to manage and track the data during the search process. RESULTS: Out of 694 articles initially identified, 25 articles met the inclusion criteria and were included in the review. Designs of the studies varied, including randomized control trials, clinical trials, and case/cohort studies. The impact of vitamin supplementation on cancer risk varied. Several studies found that certain B vitamin supplementation lowered cancer risk: B9 and B6 in nasopharyngeal carcinoma (n = 1200 patients) and in pancreatic cancer (n = 258 patients); B3 in hepatocellular carcinoma (n = 494,860 patients); B6 in breast cancer (n = 27,853 patients); and B9 in BRCA1-positive breast cancer (n = 400 patients). However, some studies found that certain B vitamin supplementation increased the risk or negative outcomes of cancer: B6 during nasopharyngeal carcinoma treatment (n = 592 patients); B6 in risk of hepatocellular carcinoma (n = 494,860 patients); and B9 plasma levels in breast cancer (n = 164 patients). Due to the many adverse effects that occur in cancer treatment, the effectiveness of Vitamin B supplementation in alleviating adverse effects was evaluated. In two separate studies, Vitamin B6 and Vitamin B12 supplementation with acupuncture was found to be effective as adjunct therapies aimed to reduce chemotherapy-induced peripheral neuropathy (n = 23 patients and n = 104 patients, respectively). No significant findings were established regarding B vitamin supplementation in chemotherapy-induced hand-foot syndrome. CONCLUSIONS: In this systematic review we concluded that B vitamin supplements have varying data regarding safety and efficacy in cancer. Taking into account the etiology of the cancer, the specific B-vitamin, and the presence of any side effects could help guide utilization of the data found in this review. Large, randomized controlled trials are needed to confirm these findings among various cancer diagnoses and stages. Given the widespread utilization of supplements, healthcare providers should understand the safety and efficacy of vitamin B supplementation to address questions that arise in caring for those with cancer.

Electronic properties of single-crystalline Fe4O5.

We synthesized single and polycrystals of iron oxide with an unconventional Fe4O5 stoichiometry under high-pressure high-temperature (HP-HT) conditions. The crystals of Fe4O5 had a CaFe3O5-type structure composed of linear chains of iron with octahedral and trigonal-prismatic oxygen coordinations. We investigated the electronic properties of this mixed-valence oxide using several experimental techniques, including measurements of electrical resistivity, the Hall effect, magnetoresistance, and thermoelectric power (Seebeck coefficient), X-ray absorption near edge spectroscopy (XANES), reflectance and absorption spectroscopy, and single-crystal X-ray diffraction. Under ambient conditions, the single crystals of Fe4O5 demonstrated a semimetal electrical conductivity with nearly equal partial contributions of electrons and holes (σn ≈ σp), in line with the nominal average oxidation state of iron as Fe2.5+. This finding suggests that both the octahedral and trigonal-prismatic iron cations contribute to the electrical conductivity of Fe4O5via an Fe2+/Fe3+ polaron hopping mechanism. A moderate deterioration of crystal quality shifted the dominant electrical conductivity to n-type and considerably worsened the conductivity. Thus, alike magnetite, Fe4O5 with equal numbers of Fe2+ and Fe3+ ions can serve as a prospective model for other mixed-valence transition-metal oxides. In particular, it could help in the understanding of the electronic properties of other recently discovered mixed-valence iron oxides with unconventional stoichiometries, many of which are not recoverable to ambient conditions; it can also help in designing novel more complex mixed-valence iron oxides.

In-Situ Electrochemical Exfoliation and Methylation of Black Phosphorus into Functionalized Phosphorene Nanosheets.

Two-dimensional black phosphorus (BP) has attracted great attention as a perspective material for various applications. The chemical functionalization of BP is an important pathway for the preparation of materials with improved stability and enhanced intrinsic electronic properties. Currently, most of the methods for BP functionalization with organic substrates require either the use of low-stable precursors of highly reactive intermediates or the use of difficult-to-manufacture and flammable BP intercalates. Herein we report a facile route for simultaneous electrochemical exfoliation and methylation of BP. Conducting the cathodic exfoliation of BP in the presence of iodomethane makes it possible to generate highly active methyl radicals, which readily react with the electrode's surface yielding the functionalized material. The covalent functionalization of BP nanosheets with the P-C bond formation has been proven by various microscopic and spectroscopic methods. The functionalization degree estimated by solid-state 31P NMR spectroscopy analysis reached 9.7%.

Antihypothyroid Effect of Salidroside.

In terms of prevalence, thyroid pathology, associated both with a violation of the gland function and changes in its structure, occupies one of the main places in clinical endocrinology. The problem of developing low-toxic and highly effective herbal preparations for the correction of thyroid hypofunction and its complications is urgent. Salidroside is a glucoside of tyrosol, found mostly in the roots of Rhodiola spp., and has various positive biological activities. The purpose of this study was to study the antihypothyroid potential of salidrosid-containing extract from R. semenovii roots, which was evaluated on a mercazolyl hypothyroidism model. We showed that extract containing salidroside is a safe and effective means of hypothyroidism correction, significantly reducing (p ≤ 0.001) the level of thyroid-stimulating hormone and increasing the level of thyroid hormones. The combined use of R. semenovii extract with potassium iodide enhances the therapeutic effect of the extract by 1.3-times.

Better maternity care pathways in pregnancies after stillbirth or neonatal death: a feasibility study.

BACKGROUND: Around 1 in 150 babies are stillborn or die in the first month of life in the UK. Most women conceive again, and subsequent pregnancies are often characterised by feelings of stress and anxiety, persisting beyond the birth. Psychological distress increases the risk of poor pregnancy outcomes and longer-term parenting difficulties. Appropriate emotional support in subsequent pregnancies is key to ensure the wellbeing of women and families. Substantial variability in existing care has been reported, including fragmentation and poor communication. A new care package improving midwifery continuity and access to emotional support during subsequent pregnancy could improve outcomes. However, no study has assessed the feasibility of a full-scale trial to test effectiveness in improving outcomes and cost-effectiveness for the National Health Service (NHS). METHODS: A prospective, mixed-methods pre-and post-cohort study, in two Northwest England Maternity Units. Thirty-eight women, (≤ 20 weeks' gestation, with a previous stillbirth, or neonatal death) were offered the study intervention (allocation of a named midwife care coordinator and access to group and online support). Sixteen women receiving usual care were recruited in the 6 months preceding implementation of the intervention. Outcome data were collected at 2 antenatal and 1 postnatal visit(s). Qualitative interviews captured experiences of care and research processes with women (n = 20), partners (n = 5), and midwives (n = 8). RESULTS: Overall recruitment was 90% of target, and 77% of women completed the study. A diverse sample reflected the local population, but non-English speaking was a barrier to participation. Study processes and data collection methods were acceptable. Those who received increased midwifery continuity valued the relationship with the care coordinator and perceived positive impacts on pregnancy experiences. However, the anticipated increase in antenatal continuity for direct midwife contacts was not observed for the intervention group. Take-up of in-person support groups was also limited. CONCLUSIONS: Women and partners welcomed the opportunity to participate in research. Continuity of midwifery care was supported as a beneficial strategy to improve care and support in pregnancy after the death of a baby by both parents and professionals. Important barriers to implementation included changes in leadership, service pressures and competing priorities. TRIAL REGISTRATION: ISRCTN17447733 first registration 13/02/2018.

GCN5 maintains muscle integrity by acetylating YY1 to promote dystrophin expression.

Protein lysine acetylation is a post-translational modification that regulates protein structure and function. It is targeted to proteins by lysine acetyltransferases (KATs) or removed by lysine deacetylases. This work identifies a role for the KAT enzyme general control of amino acid synthesis protein 5 (GCN5; KAT2A) in regulating muscle integrity by inhibiting DNA binding of the transcription factor/repressor Yin Yang 1 (YY1). Here we report that a muscle-specific mouse knockout of GCN5 (Gcn5skm-/-) reduces the expression of key structural muscle proteins, including dystrophin, resulting in myopathy. GCN5 was found to acetylate YY1 at two residues (K392 and K393), disrupting the interaction between the YY1 zinc finger region and DNA. These findings were supported by human data, including an observed negative correlation between YY1 gene expression and muscle fiber diameter. Collectively, GCN5 positively regulates muscle integrity through maintenance of structural protein expression via acetylation-dependent inhibition of YY1. This work implicates the role of protein acetylation in the regulation of muscle health and for consideration in the design of novel therapeutic strategies to support healthy muscle during myopathy or aging.

Ultrasound-guided Procedures Allow Delay of Definitive Treatment for Core Muscle Injuries.

INTRODUCTION: Core muscle injuries (CMI) are common in every sport. To minimize lost playing time, providers apply various nonsurgical treatments, including platelet-rich plasma, corticosteroids, ultrasound (US)-guided percutaneous tenotomy, and prolotherapy. Limited data exist with regard to their effectiveness. We chose to review a cohort of consecutive professional and collegiate athletes who sustained CMI at various points within their seasons and underwent a combination of US-guided percutaneous needle "tenotomy" and corticosteroid injections to complete the remainder of their seasons. METHODS: Twenty-five consecutive collegiate or professional athletes with CMI involving the rectus abdominis-adductor aponeurotic plate were included in this retrospective study. Athletes with concomitant symptomatic hip femoroacetabular impingement were included in the study. The primary outcome measure was whether athletes completed their seasons. Secondary measures were weeks played after the procedures (delay until surgery), need for repeat procedures, and outcomes after eventual surgery. Postoperative performance was assessed via interviews at 6 wk and 6 months postoperatively. RESULTS: Twenty-one of 25 (84%) athletes completed their seasons. On average, athletes returned to play 3 d (range, 1-9 d) after the procedures. Surgical repair was delayed a mean of 18 wk (range, 2-44 wk). Seven athletes had concomitant symptomatic femoroacetabular impingement and six underwent combined hip arthroscopy and core muscle repairs. Among 17 patients who eventually had core muscle surgery alone (no hip surgery), 82% (14 of 17) reported performing at their preinjury level at 6 wk. At 6 months, 96% of postop athletes (22 of 23) reported performing at their preinjury level. CONCLUSIONS: Temporizing CMI with US-guided percutaneous tenotomy and corticosteroid injections is effective in allowing continued sport participation among high-level athletes and does not negatively affect postoperative outcomes.

Multiomics approach reveals a role of translational machinery in shaping maize kernel amino acid composition.

Maize (Zea mays) seeds are a good source of protein, despite being deficient in several essential amino acids. However, eliminating the highly abundant but poorly balanced seed storage proteins has revealed that the regulation of seed amino acids is complex and does not rely on only a handful of proteins. In this study, we used two complementary omics-based approaches to shed light on the genes and biological processes that underlie the regulation of seed amino acid composition. We first conducted a genome-wide association study to identify candidate genes involved in the natural variation of seed protein-bound amino acids. We then used weighted gene correlation network analysis to associate protein expression with seed amino acid composition dynamics during kernel development and maturation. We found that almost half of the proteome was significantly reduced during kernel development and maturation, including several translational machinery components such as ribosomal proteins, which strongly suggests translational reprogramming. The reduction was significantly associated with a decrease in several amino acids, including lysine and methionine, pointing to their role in shaping the seed amino acid composition. When we compared the candidate gene lists generated from both approaches, we found a nonrandom overlap of 80 genes. A functional analysis of these genes showed a tight interconnected cluster dominated by translational machinery genes, especially ribosomal proteins, further supporting the role of translation dynamics in shaping seed amino acid composition. These findings strongly suggest that seed biofortification strategies that target the translation machinery dynamics should be considered and explored further.

Virtual Screening in Search for a Chemical Probe for Angiotensin-Converting Enzyme 2 (ACE2).

We elaborate new models for ACE and ACE2 receptors with an excellent prediction power compared to previous models. We propose promising workflows for working with huge compound collections, thereby enabling us to discover optimized protocols for virtual screening management. The efficacy of elaborated roadmaps is demonstrated through the cost-effective molecular docking of 1.4 billion compounds. Savings of up to 10-fold in CPU time are demonstrated. These developments allowed us to evaluate ACE2/ACE selectivity in silico, which is a crucial checkpoint for developing chemical probes for ACE2.

Association Between Intraventricular Alteplase Use and Parenchymal Hematoma Volume in Patients With Spontaneous Intracerebral Hemorrhage and Intraventricular Hemorrhage.

Importance: Intraventricular thrombolysis reduces intraventricular hemorrhage (IVH) volume in patients with spontaneous intracerebral hemorrhage (ICH), but it is unclear if a similar association with parenchymal ICH volume exists. Objective: To evaluate the association between intraventricular alteplase use and ICH volume as well as the association between a change in parenchymal ICH volume and long-term functional outcomes. Design, Setting, and Participants: This cohort study was a post hoc exploratory analysis of data from the Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage phase 3 randomized clinical trial with blinded outcome assessments. Between September 1, 2009, and January 31, 2015, patients with ICH and IVH were randomized to receive either intraventricular alteplase or normal saline via an external ventricular drain. Participants with primary IVH were excluded. Data analyses were performed between January 1 and June 30, 2021. Exposure: Randomization to receive intraventricular alteplase. Main Outcomes and Measures: The primary outcome was the change in parenchymal ICH volume between the hematoma stability and end-of-treatment computed tomography scans. Secondary outcomes were a modified Rankin Scale score higher than 3 and mortality, both of which were assessed at 6 months. The association between alteplase and change in parenchymal ICH volume was assessed using multiple linear regression, whereas the associations between change in parenchymal ICH volume and 6-month outcomes were assessed using multiple logistic regression. Prespecified subgroup analyses were performed for baseline IVH volume, admission ICH volume, and ICH location. Results: A total of 454 patients (254 men [55.9%]; mean [SD] age, 59 [11] years) were included in the study. Of these patients, 230 (50.7%) were randomized to receive alteplase and 224 (49.3%) to receive normal saline. The alteplase group had a greater mean (SD) reduction in parenchymal ICH volume compared with the saline group (1.8 [0.2] mL vs 0.4 [0.1] mL; P < .001). In the primary analysis, alteplase use was associated with a change in the parenchymal ICH volume in the unadjusted analysis per 1-mL change (ß, 1.37; 95% CI, 0.92-1.81; P < .001) and in multivariable linear regression analysis that was adjusted for demographic characteristics, stability ICH and IVH volumes, ICH location, and time to first dose of study drug per 1-mL change (ß, 1.20; 95% CI, 0.79-1.62; P < .001). In the secondary analyses, no association was found between change in parenchymal ICH volume and poor outcome (odds ratio [OR], 0.97; 95% CI 0.87-1.10; P = .64) or mortality (OR, 0.97; 95% CI 0.99-1.08; P = .59). Similar results were observed in the subgroup analyses. Conclusions and Relevance: This study found that intraventricular alteplase use in patients with a large IVH was associated with a small reduction in parenchymal ICH volume, but this association did not translate into improved functional outcomes or mortality. Intraventricular thrombolysis should be examined in patients with moderate to large ICH with IVH, especially in a thalamic location.

Left Ventricular Dysfunction Among Patients With Embolic Stroke of Undetermined Source and the Effect of Rivaroxaban vs Aspirin: A Subgroup Analysis of the NAVIGATE ESUS Randomized Clinical Trial.

Importance: It is uncertain whether anticoagulation is superior to aspirin at reducing recurrent stroke in patients with recent embolic strokes of undetermined source (ESUS) and left ventricular (LV) dysfunction. Objective: To determine whether anticoagulation is superior to aspirin in reducing recurrent stroke in patients with ESUS and LV dysfunction. Design, Setting, and Participants: Post hoc exploratory analysis of data from the New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial vs Aspirin to Prevent Embolism in ESUS (NAVIGATE ESUS) trial, a randomized, phase 3 clinical trial with enrollment from December 2014 to September 2017. The study setting included 459 stroke recruitment centers in 31 countries. Patients 50 years or older who had neuroimaging-confirmed ESUS between 7 days and 6 months before screening were eligible. Of the 7213 NAVIGATE ESUS participants, 7107 (98.5%) had a documented assessment of LV function at study entry and were included in the present analysis. Data were analyzed in January 2021. Interventions: Participants were randomized to receive either 15 mg of rivaroxaban or 100 mg of aspirin once daily. Main Outcomes and Measures: The study examined whether rivaroxaban was superior to aspirin at reducing the risk of (1) the trial primary outcome of recurrent stroke or systemic embolism and (2) the trial secondary outcome of recurrent stroke, systemic embolism, myocardial infarction, or cardiovascular mortality during a median follow-up of 10.4 months. LV dysfunction was identified locally through echocardiography and defined as moderate to severe global impairment in LV contractility and/or a regional wall motion abnormality. A Cox proportional hazards model was used to assess for treatment interaction and to estimate the hazard ratios for those randomized to rivaroxaban vs aspirin by LV dysfunction status. Results: LV dysfunction was present in 502 participants (7.1%). Of participants with LV dysfunction, the mean (SD) age was 67 (10) years, and 130 (26%) were women. Among participants with LV dysfunction, annualized primary event rates were 2.4% (95% CI, 1.1-5.4) in those assigned to rivaroxaban vs 6.5% (95% CI, 4.0-11.0) in those assigned aspirin. Among the 6605 participants without LV dysfunction, rates were similar between those assigned to rivaroxaban (5.3%; 95% CI, 4.5-6.2) vs aspirin (4.5%; 95% CI, 3.8-5.3). Participants with LV dysfunction assigned to rivaroxaban vs aspirin had a lower risk of the primary outcome (hazard ratio, 0.36; 95% CI, 0.14-0.93), unlike those without LV dysfunction (hazard ratio, 1.16; 95% CI, 0.93-1.46) (P for treatment interaction = .03). Results were similar for the secondary outcome. Conclusions and Relevance: In this post hoc exploratory analysis, rivaroxaban was superior to aspirin in reducing the risk of recurrent stroke or systemic embolism among NAVIGATE ESUS participants with LV dysfunction. Trial Registration: ClinicalTrials.gov Identifier: NCT02313909.

A BCI-Based Vibrotactile Neurofeedback Training Improves Motor Cortical Excitability During Motor Imagery.

In this study, we address the issue of whether vibrotactile feedback can enhance the motor cortex excitability translated into the plastic changes in local cortical areas during motor imagery (MI) BCI-based training. For this purpose, we focused on two of the most notable neurophysiological effects of MI - the event-related desynchronization (ERD) level and the increase in cortical excitability assessed with navigated transcranial magnetic stimulation (nTMS). For TMS navigation, we used individual high-resolution 3D brain MRIs. Ten BCI-naive and healthy adults participated in this study. The MI (rest or left/right hand imagery using Graz-BCI paradigm) tasks were performed separately in the presence and absence of feedback. To investigate how much the presence/absence of vibrotactile feedback in MI BCI-based training could contribute to the sensorimotor cortical activations, we compared the MEPs amplitude during MI after training with and without feedback. In addition, the ERD levels during MI BCI-based training were investigated. Our findings provide evidence that applying vibrotactile feedback during MI training leads to (i) an enhancement of the desynchronization level of mu-rhythm EEG patterns over the contralateral motor cortex area corresponding to the MI of the non-dominant hand; (ii) an increase in motor cortical excitability in hand muscle representation corresponding to a muscle engaged by the MI.

Factors influencing health behaviour change during pregnancy: a systematic review and meta-synthesis.

Pregnancy is an opportune time for women to make healthy changes to their lifestyle, however, many women struggle to do so. Multiple reasons have been posited as to why this may be. This review aimed to synthesise this literature by identifying factors that influence women's health behaviour during pregnancy, specifically in relation to dietary behaviour, physical activity, smoking, and alcohol use. Bibliographic databases (MEDLINE, PsycINFO, CINAHL-P, MIDIRS) were systematically searched to retrieve studies reporting qualitative data regarding women's experiences or perceptions of pregnancy-related behaviour change relating to the four key behaviours. Based on the eligibility criteria, 30,852 records were identified and 92 studies were included. Study quality was assessed using the CASP tool and data were thematically synthesised. Three overarching themes were generated from the data. These were (1) A time to think about 'me', (2) Adopting the 'good mother' role, and (3) Beyond mother and baby. These findings provide an improved understanding of the various internal and external factors influencing women's health behaviour during the antenatal period. This knowledge provides the foundations from which future pregnancy-specific theories of behaviour change can be developed and highlights the importance of taking a holistic approach to maternal behaviour change in clinical practice.

The Stage at Presentation and Oncologic Outcomes for Agent Orange Exposed and Non-Exposed United States Veterans Diagnosed With Prostate Cancer.

INTRODUCTION: It is unknown if Agent Orange (AO)-exposed veterans have worse outcomes than unexposed Veterans after prostate cancer treatment. We evaluated oncologic outcomes based on AO exposure history, accounting for known prognostic covariates not previously studied. METHODS: US military Veterans diagnosed with prostate adenocarcinoma born between 1930 and 1956 were identified from our prospectively gathered institutional database. Evaluable patients had to have known AO exposure status, age, National Comprehensive Cancer Network risk group, Charlson comorbidity score, smoking status, and type of initial therapy. The risk of death, metastasis, and progression stratified by initial therapy was analyzed using Cox regression. RESULTS: Seventy AO-exposed and 561 non-exposed Veterans were identified (median follow-up, 10.0 years). AO-exposed veterans (AOeV) were slightly younger (64.0 vs 65.7 years; P = .013) at diagnosis and presented at more advanced stages (stage 4: 14.3% vs 2.5%) than non-AOeV. There was no difference for overall survival (hazard ratio [HR], 0.86; P = .576; metastasis-free survival (HR, 1.5; P = .212), or progression-free survival (HR, 0.67; P = .060) between AOeV vs non-AOeV in analyses stratified by treatment received accounting for other prognostic covariates. Cigarette smoking was associated with a 2- to 3-fold increased risk of death over those who quit or never smoked. CONCLUSION: Although AOeV do present at a younger age and higher clinical stages than non-AOeV, the oncologic outcomes after accounting for treatments received and other prognostic covariates are similar.

Five-Year Surveillance of Vitamin D Levels in NCAA Division I Football Players: Risk Factors for Failed Supplementation.

BACKGROUND: Monitoring vitamin D levels in athletes and determining their response to supplementation in cases of deficiency is thought to be necessary to modulate the risks associated with vitamin D deficiency. HYPOTHESIS/PURPOSE: To report the results of a 5-year-long surveillance program of vitamin D in the serum of football players on a National Collegiate Athletic Association (NCAA) Division I team and to examine whether factors including age, body mass index (BMI), race, position played, and supplement type would affect the response to 12-month oral vitamin D replacement therapy in athletes with deficiency. We hypothesized that yearly measurements would decrease the proportion of athletes with vitamin D insufficiency over the years and that the aforementioned factors would affect the response to the supplementation therapy. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: We measured serum 25(OH)D levels (25-hydroxyvitamin D) in 272 NCAA Division I football players from our institution annually between 2012 and 2017. Athletes with insufficient vitamin D levels (<32 ng/mL) received supplementation with vitamin D3 alone or combined vitamin D3/D2. The percentage of insufficient cases between the first 2 years and last 2 years of the program was compared, and yearly team averages of vitamin D levels were calculated. Associations between player parameters (age, BMI, race, team position, supplement type) and failed supplementation were evaluated. RESULTS: The prevalence of vitamin D insufficiency decreased significantly during the study period, from 55.5% in 2012-2013 to 30.7% in 2016-2017 (P = .033). The mean 25(OH)D level in 2012 was 36.3 ng/mL, and this increased to 40.5 ng/mL in 2017 (P < .001); however, this increase was not steady over the study period. Non-Hispanic athletes and quarterbacks had the highest average 25(OH)D levels, and Black players and running backs had the lowest overall levels. There were no significant differences in age, BMI, race, or playing position between athletes with and without failed vitamin D supplementation. Athletes receiving vitamin D3 alone had a more successful rate of conversion (48.15%) than those receiving combined vitamin D3/D2 (22.22%; P = .034). CONCLUSION: To decrease the prevalence of vitamin D deficiency in football players, serum vitamin D measurements should be performed at least once a year, and oral supplementation therapy should be provided in cases of deficiency. Black players might be at increased risk of vitamin D insufficiency. Oral vitamin D3 may be more effective in restoring vitamin D levels than combined vitamin D3/D2 therapy.