Neural Manifold Constraint for Spike Prediction Models Under Behavioral Reinforcement.

Spike prediction models effectively predict downstream spike trains from upstream neural activity for neural prostheses. Such prostheses could potentially restore damaged neural communication pathways using predicted patterns to guide electrical stimulations on downstream. Since the ground truth of downstream neural activity is unavailable for subjects with the damage, reinforcement learning (RL) with behavior-level rewards becomes necessary for model training. However, existing models do not involve any constraint on the generated firing patterns and neglect the correlations among neural activities. Thus, the model outputs can greatly deviate from the natural range of neural activities, causing concerns for clinical usage. This study proposes the neural manifold constraint to solve this problem, shaping RL-generated spike trains in the feature space. The constraint terms describe the first and second order statistics of the neural manifold estimated from neural recordings during subjects' freely moving period. Then, the models can be optimized within the neural manifold by behavioral reinforcement. We test the method to predict primary motor cortex (M1) spikes from medial prefrontal (mPFC) spikes when rats perform the two-lever discrimination task. Results show that the neural activity generated by constrained models resembles the real M1 recordings. Compared with models without constraints, our approach achieves similar behavioral success rates, but reduces the mean squared error of neural firing by 61%. The constraints also increase the model's robustness across data segments and induce realistic neural correlations. Our method provides a promising tool to restore transregional communication with high behavioral performance and more realistic microscopic patterns.

SPARCL1 promotes chondrocytes extracellular matrix degradation and inflammation in osteoarthritis via TNF/NF-κB pathway.

Objectives: SPARCL1 is a matricellular protein that mediates the cell-matrix interactions and participates in physiological processes such as cell adhesion, differentiation and proliferation. However, its role in chondrocyte and osteoarthritis (OA) progression has not been fully characterized. We aimed to evaluate the effects of SPARCL1 on OA through in vitro and in vivo experiments. Methods: Expression of SPARCL1 was examined in 55 paired human OA samples. Effects of Sparcl1 on chondrocytes were identified in vitro. Intra-articular injection was performed in an anterior cruciate ligament transection (ACLT) mouse model. Alterations of SPARCL1-mediated signaling pathway were identified by RNA-seq analysis. qPCR and western-blot were used to demonstrate the potential signaling pathway. Results: SPARCL1 expression in the OA cartilage was increased compared with undamaged cartilage. Recombinant Sparcl1 protein induced extracellular matrix degradation in chondrocytes. Furthermore, intra-articular injection of recombinant Sparcl1 protein in ACLT mice could promote OA pathogenesis. Mechanistically, Sparcl1 activated TNF/NF-κB pathway and consequently led to increased transcription of inflammatory factors and catabolism genes of cartilage, which could be reversed by NF-κB inhibitor BAY 11-7082. Conclusion: SPARCL1 could promote extracellular matrix degradation and inflammatory response to accelerate OA progression via TNF/NF-κB pathway. The translational potential of this article: The current research could help to gain further insights into the underlying molecular mechanism in OA development, and provides a biological rationale for the use of SPARCL1 as a potential therapeutic target of OA.

Correction: Childhood cancer survival in the highly vulnerable population of South Texas: A cohort study.

[This corrects the article DOI: 10.1371/journal.pone.0278354.].

Goat milk exosomal microRNAs alleviate LPS-induced intestinal inflammation in mice.

Intestinal inflammation is a common digestive system disease. Milk-derived exosomes can participate in intercellular communication and transport a variety of bioactive components, and the microRNAs (miRNAs) they carry play important roles in a variety of biological processes in the body. At present, the preventive effect and mechanism of action of goat milk exosomes and their derived miRNAs on intestinal inflammation are still unclear. In this study, the protective effect of goat milk exosomes on LPS-induced intestinal inflammation was investigated using mouse intestinal inflammation model and IEC-6 cell inflammation model. Small RNA sequencing was used to analyze the miRNA expression profile of goat milk exosomes. In this study, C-Exo and M-Exo alleviated intestinal inflammation by reducing the LPS-induced release of proinflammatory cytokines, inhibiting the increase in the NLRP3 protein and the activation of the TLR4/NFκB signaling pathway. C-Exo has a more significant inhibitory effect on them, and better therapeutic efficacy than M-Exo. Notably, the target genes of miRNAs in C-Exo and M-Exo were significantly enriched in immune-related pathways. Furthermore, their derived miR-26a-5p and miR-30a-5p were found to ameliorate the IEC-6 inflammatory response. These findings suggest that miRNAs in goat milk exosomes have the potential to attenuate LPS-induced intestinal inflammation.

A high burden of diabetes and ankle brachial index abnormalities exists in Mexican Americans in South Texas.

Ethnic differences exist in the United States in the interrelated problems of diabetes (DM), peripheral arterial disease (PAD), and leg amputations. The purpose of this study was to determine the prevalence and risk factor associations for subclinical PAD in a population sample of Mexican Americans using the ankle brachial (ABI) index. The ABI-High (higher of the two ankle pressures/highest brachial pressure) and ABI-Low (lower of the two ankle pressures/highest brachial pressure) were calculated to define PAD. Toe brachial index (TBI) was also calculated. 746 participants were included with an age of 53.4 ± 0.9 years, 28.3 % had diabetes mellitus (DM), 12.6 % were smokers, and 51.2 % had hypertension (HTN). Using ABI-High ≤ 0.9, the prevalence of PAD was 2.7 %. This rose to 12.7 % when an ABI-Low ≤ 0.9 was used; 4.0 % of the population had an ABI-High > 1.4. The prevalence of TBI < 0.7 was 3.9 %. DM was a significant risk factor for ABI-High ≤ 0.9 and ABI-High > 1.4, and TBI < 0.7. Increased age, HTN, smoking was associated with ABI-High ≤ 0.9, while being male was associated with ABI-High > 1.4. Increased age, smoking, and lower education were all associated with abnormal TBI. Despite relatively younger mean age than other studied Hispanic cohorts, the present population has a high burden of ABI abnormalities. DM was a consistent risk factor for PAD. These abnormalities indicate an important underlying substrate of vascular and metabolic disease that may predispose this population to the development of symptomatic PAD and incident amputations.

Effect of vitrification on protein O-GlcNAcylation in mouse metaphase II oocytes.

In brief: Oocyte vitrification leads to DNA hypomethylation, which results in defect in early embryo development. This study reveals that oocyte vitrification impairs the DNA methylation pattern by influencing protein O-GlcNAcylation. Abstract: Oocyte vitrification leads to decreased DNA methylation levels, which impairs the quality and the developmental potential of oocytes. However, the underlying molecular mechanism still need to be further revealed. In this study, mouse metaphase II (M II) oocytes were frozen by vitrification technology, while fresh oocytes were used as the control group. The effect of oocyte vitrification on protein O-GlcNAcylation and its impact on the developmental potential of oocytes were elucidated. We found that the protein O-GlcNAcylation levels were significantly increased in vitrified oocytes. Increase of protein O-GlcNAcylation levels in control oocytes by PUGNAc (an O-GlcNAcase inhibitor) decreases blastocyst rate after parthenogenetic activation (20.82% in PUGNAc-treated group; 53.82% in control group, P < 0.05). We also discovered that DNA methylation was disrupted in two-cell embryos derived from vitrified oocytes, resulting in decreased 5mC and increased 5hmC, showing similar phenotypes to that derived from PUGNAc-treated oocytes. In vitrified and PUGNAc-treated oocytes, O-GlcNAcylated TET3 was significantly increased. Notably, by inhibiting protein O-GlcNAcylation in vitrified oocytes using OSMI1 (an O-GlcNAc transferase inhibitor) we restored the DNA methylation in two-cell embryos and ameliorated the developmental defects in early embryo. Thus, elevated protein O-GlcNAcylation in vitrified oocytes is an essential contributor to their declining embryonic developmental potential. Modulation of protein O-GlcNAcylation improves the developmental potential of vitrified oocytes.

State-space Model Based Inverse Reinforcement Learning for Reward Function Estimation in Brain-machine Interfaces.

The use of reinforcement learning (RL) in brain machine interfaces (BMIs) is considered to be a promising method for neural decoding. One key component of RL-based BMIs is the reward signal, which is used to guide decoders to update the parameters. However, designing effective and efficient rewards can be challenging, especially for complex tasks. Inverse reinforcement learning (IRL) is a method that has been proposed to estimate the internal reward function from subjects' neural activity. However, multi-channel neural activity, which may encode many sources of information, builds a large dimensions of state-action space, making it difficult to directly apply IRL methods in BMI systems. In this paper, we propose a state-space model based inverse Q-learning (SSM-IQL) method to improve the performance of the existing IRL method. The state-space model is designed to extract hidden brain state from high-dimensional neural activity. We tested the proposed method on real data collected from rats during a two-lever discrimination task. Preliminary results show that SSM-IQL provides a more accurate and stable estimation of the internal reward function than the traditional IQL algorithm. This suggests that the use of state-space model in IRL method has potential to improve the design of RL-based BMIs.

Applying Neural Manifold Constraint on Point Process Model for Neural Spike Prediction.

Neural prostheses can compensate for functional losses caused by blocked neural pathways by modeling neural activities among cortical areas. Existing methods generally utilize point process models to predict neural spikes from one area to another, and optimize the model by maximizing the log-likelihood between model predictions and recorded activities of individual neurons. However, single-neuron recordings can be distorted, while neuron population activity tends to reside within a stable subspace called the neural manifold, which reflects the connectivity and correlation among output neurons. This paper proposes a neural manifold constraint to modify the loss function for model training. The constraint term minimizes the distance from model predictions to the empirical manifold to amend the model predictions from distorted recordings. We test our methods on synthetic data with distortion on output spike trains and evaluate the similarity between model predictions and original output spike trains by the Kolmogorov-Smirnov test. The results show that the models trained with constraint have higher goodness-of-fit than those trained without constraint, which indicates the potential better approach for neural prostheses in noisy environments.

Catalpol ameliorates LPS-induced inflammatory response by activating AMPK/mTOR signaling pathway in rat intestinal epithelial cells.

Intestinal inflammation is a common clinical intestinal disease. Catalpol, a natural iridoid compound, has been shown to have anti-inflammatory, anti-oxidant and anti-apoptotic functions, but the mechanism of its protection against intestinal inflammation is still unclear. This study investigated the protective effect and potential mechanism of catalpol on the lipopolysaccharide (LPS)-induced inflammatory response of intestinal epithelial cell-6 (IEC-6). The results showed that catalpol could inhibit LPS-induced inflammatory response by dose-dependently reducing the release of inflammatory factors, such as tumor necrosis (TNF)-α, interleukin (IL)-1ß and IL-6, and inhibiting the nuclear factor kappa-B (NF-κB) signaling pathway. Catalpol ameliorated cellular oxidative stress by reducing reactive oxygen species (ROS) and malondialdehyde (MDA) levels and increasing superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) expression. Meanwhile, catalpol also inhibited cell apoptosis, decreased the expression of B-cell lymphoma 2 (Bcl-2) - associated X (Bax), caspase 3 and caspase 9, and increased the expression of Bcl-2. This study found that catalpol activates AMP-activated protein kinase (AMPK) signaling pathway and inhibit mammalian target of rapamycin (mTOR) phosphorylationthe. In a further study, after inhibiting AMPK with dorsomorphin, the anti-inflammatory effects of catalpol were significantly reduced. Therefore, catalpol ameliorates LPS-induced inflammatory response by activating AMPK/mTOR signaling pathway in IEC-6 cells.

Specific types of femoral head fractures: be alert for pre-, intra-, and post-operative ipsilateral femoral neck fractures following fracture-dislocation of the femoral head.

PURPOSE: Ipsilateral femoral head and neck fractures (iFHNFs) are rare types of fractures that confer extremely poor prognosis among femoral head fractures (FHFs). Owing to the rarity of FHFs, it is challenging to diagnose iFHNFs. In addition, the clinical features of iFHNF have not yet been comprehensively elucidated. Therefore, this retrospective study aimed to summarize and analyze the clinical characteristics of iFHNF using a clinical diagnostic simulation based on a prospectively maintained database. METHODS: Clinical data of consecutive patients with FHFs, including gender, age, injury side, and associated injuries, were collected and analyzed from a prospectively maintained orthopedic database at a large level-I trauma center for a clinical diagnostic simulation. Patients were stratified according to the presence or absence of iFHNF. Moreover, propensity score matching (PSM) was used to create 1:1 age- and gender-matched couples. Lastly, clinical factors were compared and identified between the two groups before and after matching. RESULTS: A total of 218 FHF patients were included. Fifteen patients were diagnosed with ipsilateral femoral neck fractures (iFNFs), including preoperative, intraoperative, and postoperative types. There were 177 male and 41 female patients, with a mean age of 40.0 ± 16.5 years. The incidence of two factors, namely acetabular fracture and posterior hip dislocation, were significantly different between the two groups (P < 0.05). Following PSM, 15 pairs of patients were generated. Comparisons revealed that the incidence of posterior hip dislocation was significantly different between the two groups (P < 0.05). CONCLUSIONS: There were three types of iFHNFs. In the context of FHFs, posterior hip dislocation was associated with iFNFs. Thus, surgeons should remain vigilant, not only intraoperatively but also postoperatively, for iFNFs following FHF and concomitant posterior hip dislocation. LEVEL OF EVIDENCE: Diagnostic level IV.

Audio-induced medial prefrontal cortical dynamics enhances coadaptive learning in brain-machine interfaces.

Objectives. Coadaptive brain-machine interfaces (BMIs) allow subjects and external devices to adapt to each other during the closed-loop control, which provides a promising solution for paralyzed individuals. Previous studies have focused on either improving sensory feedback to facilitate subject learning or developing adaptive algorithms to maintain stable decoder performance. In this work, we aim to design an efficient coadaptive BMI framework which not only facilitates the learning of subjects on new tasks with designed sensory feedback, but also improves decoders' learning ability by extracting sensory feedback-induced evaluation information.Approach. We designed dynamic audio feedback during the trial according to the subjects' performance when they were trained to learn a new behavioral task. We compared the learning performance of two groups of Sprague Dawley rats, one with and the other without the designed audio feedback to show whether this audio feedback could facilitate the subjects' learning. Compared with the traditional closed-loop in BMI systems, an additional closed-loop involving medial prefrontal cortex (mPFC) activity was introduced into the coadaptive framework. The neural dynamics of audio-induced mPFC activity was analyzed to investigate whether a significant neural response could be triggered. This audio-induced response was then translated into reward expectation information to guide the learning of decoders on a new task. The multiday decoding performance of the decoders with and without audio-induced reward expectation was compared to investigate whether the extracted information could accelerate decoders to learn a new task.Main results. The behavior performance comparison showed that the average days for rats to achieve 80% well-trained behavioral performance was improved by 26.4% after introducing the designed audio feedback sequence. The analysis of neural dynamics showed that a significant neural response of mPFC activity could be elicited by the audio feedback and the visualization of audio-induced neural patterns was emerged and accompanied by the behavioral improvement of subjects. The multiday decoding performance comparison showed that the decoder taking the reward expectation information could achieve faster task learning by 33.8% on average across subjects.Significance. This study demonstrates that the designed audio feedback could improve the learning of subjects and the mPFC activity induced by audio feedback can be utilized to improve the decoder's learning efficiency on new tasks. The coadaptive framework involving mPFC dynamics in the closed-loop interaction can advance the BMIs into a more adaptive and efficient system with learning ability on new tasks.

Can "In-Out-In" posterosuperior screws meet nutrient foramina in patients with femoral neck fractures?

BACKGROUND: The "In-Out-In" (IOI) posterosuperior screw was common in screw fixations of femoral neck fractures. The impacts of the IOI screw on the blood supply of the femoral head have not yet been clarified. The nutrient foramen was damaged when the screw was present in their corresponding cortex surface. This study aimed to evaluate the damage degrees of the nutrient foramina in the femoral neck as the IOI posterosuperior screw was placed in different posterosuperior locations. METHODS: One hundred and eight unpaired dry human cadaveric proximal femurs were scanned by a three-dimensional scanner. Digital data obtained from the proximal femur surface were employed for subsequent analysis. All nutrient foramina in the femoral neck were identified and marked in each subject. A simulation of the anteroposterior, lateral, and axial views was then performed, and regions of interest (ROIs) for IOI posterosuperior screws, with 6.5 mm diameter, were determined in the posterosuperior femoral neck on the axial graphs. Nutrient foramina were counted and analyzed in ROIs and femoral neck, and its damage from the IOI posterosuperior screw was also calculated in different conditions of screw placement. Paired t-tests were used for comparative analyses before and after damage. RESULTS: Most nutrient foramina were located in the subcapital region and the least in the basicervical region in the femoral neck, while the most were located in the transcervical and the least in the subcapital in the ROIs. In addition, most nutrient foramina in ROIs were located in the superior-posterior area of the femoral neck. There were four main locations of IOI posterosuperior screws where the decrease in the nutrient foramina was statistically significant (P < 0.01). The risk zone determined by these locations was located in a posterosuperior square of ROIs with an edge length of 9.75 mm. CONCLUSION: To minimize iatrogenic damage to the blood supply of the femoral head, screw positions could be assessed in anteroposterior and lateral radiographs using a risk zone. The IOI posterosuperior screw in ROIs can be applied to fix femoral neck fractures when feasible in clinical practice. This study could provide surgeons with more alternatives for screw placement in the posterosuperior femoral neck.

Changes in knowledge and awareness for a community-based cancer screening educational program.

BACKGROUND: Cervical cancer (CC), colorectal cancer (CRC), and breast cancer (BC) are diseases that can be prevented/detected through early test. Through educational programs, individuals can become better informed about these cancers and understand the importance of screening and early detection. However, many people, especially low-income, low-educated, uninsured minority population groups, do not have their cancer screenings at the recommended intervals and do not receive appropriate and timely follow-up of abnormal screening results or timely treatment after diagnosis. A community-based educational program was developed to improve knowledge and awareness toward the screening of the three cancer types in a South Texas underserved population. METHODS: Residents living in Laredo, Texas were invited to participate in the present educational program. From January 2020 to April 2021, participants were recruited using social media and flyer distributions in the general community. Participants received a free live web cancer education presentation delivered by bilingual community health educators, and online pre- and post-education surveys for CC, CRC, and BC separately. Pre-post changes in knowledge for individual items were compared using McNemar's chi-squared tests. RESULTS: Overall, the participants showed increases in CC (n = 237), CRC (n = 59), and BC (n = 56) screening knowledge and awareness after receiving the cancer screening education (Ps < 0.05). After receiving the cancer screening education, 85-97% of participants had an intent to talk to a healthcare provider about CC/CRC/BC screening, 88-97% had an intent to get a CC/CRC/BC screening test in the next 12 months or at the next routine appointment, and 90-97% had an intent to talk about CC/CRC/BC with their family members or friends. CONCLUSIONS: A community-based educational program culturally and linguistically tailored help increase knowledge and awareness about cervical, colorectal, and breast cancer screening, and promote positive changes in population's knowledge and awareness about the benefits of cancer screening. Future cancer screening educational programs in similar populations are warranted to reduce the risk of cervical, colorectal, and breast cancer.

Physical activity is inversely associated with overall cancer risk among college students in the United States: Results from the National College Health Assessment.

To our knowledge, this is the first epidemiologic study to examine the association between physical activity (PA) and cancer using data from the American College Health Association-National College Health Assessment (ACHA-NCHA). The goal of the study was to understand the dose-response relation between PA and cancer, as well as the associations between meeting US PA guidelines and overall cancer risk in US college students. The ACHA-NCHA provided self-reported information on demographic characteristics, PA, body mass index, smoking status, and overall cancer during 2019-2022 (n = 293,682; 0.08% cancer cases). To illustrate the dose-response relationship, a restricted cubic spline logistic regression analysis was used to evaluate the association of overall cancer with moderate-to-vigorous PA (MVPA) on a continuous basis. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals for the associations between meeting the three U.S. PA guidelines and overall cancer risk. The cubic spline observed that MVPA was inversely associated with the odds of overall cancer risk after adjusting for covariates; a one hour/week increase in moderate and vigorous PA was associated with a 1% and 5% reduced overall cancer risk, respectively. Multivariable-adjusted logistic regression analyses showed that meeting the US guidelines for aerobic PA for adults (≥150 minutes/week of moderate aerobic PA or ≥75 minutes of vigorous PA) (OR: 0.85), for PA for adults (≥2 days of muscle strengthening activity in addition to aerobic MVPA) (OR: 0.90), and for highly active adults (≥2 days of muscle strengthening activity and ≥300 minutes/week of aerobic moderate PA or 150 minutes/week of vigorous PA) (OR: 0.89) were statistically significant and inversely associated with cancer risk. MVPA, especially meeting US guidelines, may be inversely associated with overall cancer among college students in the US. To reduce cancer risks, multilevel interventions to promote US physical activity guidelines among college students are warranted.

Clinical Evaluation of Femoral Head Fractures: Which Classification Systems Have the Best Universality, Reliability, and Reproducibility?

BACKGROUND: Femoral head fractures are rare but potentially disabling injuries, and classifying them accurately and consistently can help surgeons make good choices about their treatment. However, there is no consensus as to which classification of these fractures is the most advantageous; parameters that might inform this choice include universality (the proportion of fractures that can be classified), as well as, of course, interobserver and intraobserver reproducibility. QUESTIONS/PURPOSES: (1) Which classification achieves the best universality (defined as the proportion of fractures that can be classified)? (2) Which classification delivers the highest intraobserver and interobserver reproducibility in the clinical CT assessment of femoral head fractures? (3) Based on the answers to those two questions, which classifications are the most applicable for clinical practice and research? METHODS: Between January 2011 and January 2023, 254 patients with femoral head fractures who had CT scans (CT is routine at our institution for patients who have experienced severe hip trauma) were potentially eligible for inclusion in this study, which was performed at a large Level I trauma center in China. Of those, 9% (23 patients) were excluded because of poor-quality CT images, unclosed physes, pathologic fractures, or acetabular dysplasia, leaving 91% (231 patients with 231 hips) for analysis here. Among those, 19% (45) were female. At the time of injury, the mean age was 40 ± 17 years. All fractures were independently classified by four observers according to the Pipkin, Brumback, AO/Orthopaedic Trauma Association (OTA), Chiron, and New classifications. Each observer repeated his classifications again 1 month later to allow us to ascertain intraobserver reliability. To evaluate the universality of classifications, we characterized the percentage of hips that could be classified using the definitions offered in each classification. The kappa (κ) value was calculated to determine interrater and intrarater agreement. We then compared the classifications based on the combination of universality and interobserver and intraobserver reproducibility to determine which classifications might be recommended for clinical and research use. RESULTS: The universalities of the classifications were 99% (228 of 231, Pipkin), 43% (99 of 231, Brumback), 94% (216 of 231, AO/OTA), 99% (228 of 231, Chiron), and 100% (231 of 231, New). The interrater agreement was judged as almost perfect (κ 0.81 [95% CI 0.78 to 0.84], Pipkin), moderate (κ 0.51 [95% CI 0.44 to 0.59], Brumback), fair (κ 0.28 [95% CI 0.18 to 0.38], AO/OTA), substantial (κ 0.79 [95% CI 0.76 to 0.82], Chiron), and substantial (κ 0.63 [95% CI 0.58 to 0.68], New). In addition, the intrarater agreement was judged as almost perfect (κ 0.89 [95% CI 0.83 to 0.96]), substantial (κ 0.72 [95% CI 0.69 to 0.75]), moderate (κ 0.51 [95% CI 0.43 to 0.58]), almost perfect (κ 0.87 [95% CI 0.82 to 0.91]), and substantial (κ 0.78 [95% CI 0.59 to 0.97]), respectively. Based on these findings, we determined that the Pipkin and Chiron classifications offer near-complete universality and sufficient interobserver and intraobserver reproducibility to recommend them for clinical and research use, but the other classifications (Brumback, AO/OTA, and New) do not. CONCLUSION: Based on our findings, clinicians and clinician-scientists can use either the Pipkin or Chiron classification systems to classify femoral head fractures based on CT images, with equal confidence. It seems unlikely that any new classifications will substantially outperform these, and the other available systems either lacked sufficient universality or reproducibility to recommend them for general use. LEVEL OF EVIDENCE: Level III, diagnostic study.

Food Environment Index is Inversely Associated with Gastric Cancer Incidence in the United States.

The first epidemiologic study was conducted to prospectively examine the association between Food Environment Index (FEI) and gastric cancer (GC) risk in the US. Surveillance, Epidemiology, and End Results provided information on GC incident cases diagnosed between 2000 and 2015 from 16 population-based cancer registries across the US. The county-level food environment was assessed using the FEI, an indicator of access to healthy foods (0 is worst, 10 is best). Poisson regression was used to calculate incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for the association between FEI and GC risk adjusting for individual-level and county-level covariates. Higher levels of FEI were associated with a statistically significant reduced risk for GC (n = 87,288 cases; adjusted IRR for every score increase = 0.50, 95% CI 0.35, 0.70; P < 0.001; adjusted IRR for the medium vs. low category = 0.87, 95% CI 0.81, 0.94; and adjusted IRR for the high vs. low category = 0.89, 95% CI 0.82, 0.95). These results suggest that a healthy food environment, as measured by FEI, may be a protective factor for GC in the US. To reduce the GC incidence, further strategies to improve food environment at the county level are warranted.

Disruption in Blood Pressure Control With the COVID-19 Pandemic: The PCORnet Blood Pressure Control Laboratory.

OBJECTIVE: To explore trends in blood pressure (BP) control before and during the COVID-19 pandemic. PATIENTS AND METHODS: Health systems participating in the National Patient-Centered Clinical Research Network (PCORnet) Blood Pressure Control Laboratory Surveillance System responded to data queries, producing 9 BP control metrics. Averages of the BP control metrics (weighted by numbers of observations in each health system) were calculated and compared between two 1-year measurement periods (January 1, 2019, through December 31, 2019, and January 1, 2020, through December 31, 2020). RESULTS: Among 1,770,547 hypertensive persons in 2019, BP control to <140/<90 mm Hg varied across 24 health systems (range, 46%-74%). Reduced BP control occurred in most health systems with onset of the COVID-19 pandemic; the weighted average BP control was 60.5% in 2019 and 53.3% in 2020. Reductions were also evident for BP control to <130/<80 mm Hg (29.9% in 2019 and 25.4% in 2020) and improvement in BP (reduction of 10 mm Hg in systolic BP or achievement of systolic BP <140 mm Hg; 29.7% in 2019 and 23.8% in 2020). Two BP control process metrics exhibited pandemic-associated disruption: repeat visit in 4 weeks after a visit with uncontrolled hypertension (36.7% in 2019 and 31.7% in 2020) and prescription of fixed-dose combination medications among those with 2 or more drug classes (24.6% in 2019 and 21.5% in 2020). CONCLUSION: BP control decreased substantially during the COVID-19 pandemic, with a corresponding reduction in follow-up health care visits among persons with uncontrolled hypertension. It is unclear whether the observed decline in BP control during the pandemic will contribute to future cardiovascular events.

Childhood cancer survival in the highly vulnerable population of South Texas: A cohort study.

This study examines childhood cancer survival rates and prognostic factors related to survival in the majority Hispanic population of South Texas. The population-based cohort study used Texas Cancer Registry data (1995-2017) to examine survival and prognostic factors. Cox proportional hazard models and Kaplan-Meier survival curves were used for survival analyses. The 5-year relative survival rate for 7,999 South Texas cancer patients diagnosed at 0-19 years was 80.3% for all races/ethnicities. Hispanic patients had statistically significant lower 5-year relative survival rates than non-Hispanic White (NHW) patients for male and female together diagnosed at age≥5 years. When comparing survival among Hispanic and NHW patients for the most common cancer, acute lymphocytic leukemia (ALL), the difference was most significant in the 15-19 years age range, with 47.7% Hispanic patients surviving at 5 years compared to 78.4% of NHW counterparts. The multivariable-adjusted analysis showed that males had statistically significant 13% increased mortality risk than females [hazard ratio (HR): 1.13, 95% confidence interval (CI):1.01-1.26] for all cancer types. Comparing to patients diagnosed at ages 1-4 years, patients diagnosed at age < 1 year (HR: 1.69, 95% CI: 1.36-2.09), at 10-14 year (HR: 1.42, 95% CI: 1.20-1.68), or at 15-19 years (HR: 1.40, 95% CI: 1.20-1.64) had significant increased mortality risk. Comparing to NHW patients, Hispanic patients showed 38% significantly increased mortality risk for all cancer types, 66% for ALL, and 52% for brain cancer. South Texas Hispanic patients had lower 5-year relative survival than NHW patients especially for ALL. Male gender, diagnosis at age<1 year or 10-19 years were also associated with decreased childhood cancer survival. Despite advances in treatment, Hispanic patients lag significantly behind NHW patients. Further cohort studies in South Texas are warranted to identify additional factors affecting survival and to develop interventional strategies.

[Assessment of the local blood supply when femoral neck fracture occurs:advances in the anatomy research and its clinical application].

The stability of internal fixation of femoral neck fractures can be obtained through surgical techniques, the configuration of screws and bone grafting, etc. However, the blood supply injury caused by fractures could not be completely reversed by the current medical management. Hence, the comprehensive evaluation of the residual blood supply of the femoral neck, to perioperatively avoid further iatrogenic injury, has become a hotspot. The anatomy of the extraosseous blood supply of the femoral neck has been widely reported, while its clinical application mostly involved the assessment of the medial circumflex femoral artery and retinacular arteries. However, further studies are needed to explore the prognosis of patients with these artery injuries, with different degrees, caused by femoral neck fractures. Direct observations of nutrient foramina in vivo are not possible with current clinical technologies, but it is possible to make reasonable preoperative planning to avoid subsequent femoral head necrosis based on the distribution features of nutrient foramina. The anatomy and clinical application studies of the intraosseous blood supply focused on the junction area of the femoral head and neck to probe the mechanism of femoral head necrosis. Thus, the intraosseous blood supply of other regions in the femoral neck remains to be further investigated. In addition, a blood supply evaluation system based on a three-level structure, extraosseous blood vessels, nutrient foramina, and intraosseous vascular network, could be explored to assist in the treatment of femoral neck fractures.

Diluent pH affects sperm motility via GSK3 α/ß-hexokinase pathway for the efficient enrichment of X-sperm to increase the female kids rate of dairy goats.

Dairy goats are the goats bred with the ability to produce large quantities of milk, and the increase of the female kid rate of breeding dairy goats is beneficial for milk production and economic benefits of dairy goat farms. Our previous study revealed that regulating the pH of dairy goat semen diluent to 6.2 or 7.4 respectively, the proportion of X chromosome bearing sperm (X-sperm) in the up and down layers of the tube after incubation was significantly higher than that of Y chromosome bearing sperm (Y-sperm) i.e. enriched X-sperm. In this study, fresh dairy goat semen collected in different seasons was diluted in different pH solutions to calculate the number and rate of X-sperm and to measure the functional parameters of enriched sperm. The artificial insemination experiments were performed with enriched X-sperm. The mechanisms of regulating the pH of diluent affecting sperm enrichment were further studied. The results showed that the proportion of enriched X-sperm in pH 6.2 and 7.4 diluents of sperm collected in different seasons showed no significantly different, but were significantly higher than that of the control group (pH 6.8). The in vitro functional parameters of X-sperm enriched in pH 6.2 and 7.4 diluent solution were not significantly different from those of the control group (P > 0.05). After artificial insemination with X-sperm enriched in pH7.4 diluent, the proportion of female offspring was significantly higher than that of the control group. It was found that the regulating pH of the diluent affected sperm mitochondrial activity and glucose uptake capacity via phosphorylating NF-κB and GSK3α/ß proteins. The motility activity of X-sperm was enhanced under acidic conditions and weakened under alkaline conditions, which was conducive to the effective enrichment of X-sperm. This study demonstrated that the number and proportion of X-sperm enriched using pH 7.4 diluent were elevated, and the proportion of female kids was increased. This technology can be used for the reproduction and production of dairy goats in farms at large scales.