Feasibility and limitations of combined treatment for lateral pelvic lymph node metastases in rectal cancer.

Colorectal cancer ranks among the most commonly diagnosed cancers globally, and is associated with a high rate of pelvic recurrence after surgery. In efforts to mitigate recurrence, pelvic lymph node dissection (PLND) is commonly advocated as an adjunct to radical surgery. Neoadjuvant chemoradiotherapy (NACRT) is a therapeutic approach employed in managing locally advanced rectal cancer, and has been found to increase the survival rates. Chua et al have proposed a combination of NACRT with selective PLND for addressing lateral pelvic lymph node metastases in rectal cancer patients, with the aim of reducing recurrence and improving survival outcomes. Nevertheless, certain studies have indicated that the addition of PLND to NACRT and total mesorectal excision did not yield a significant reduction in local recurrence rates or improvement in survival. Consequently, meticulous patient selection and perioperative chemotherapy may prove indispensable in ensuring the efficacy of PLND.

The Gene Expression Profiles Associated with Maternal Nicotine Exposure in the Liver of Offspring Mice.

This study aims to investigate the effect of maternal nicotine exposure on the gene expression profiles in the liver of offspring mice. Pregnant mice were subcutaneously injected with either saline vehicle or nicotine twice a day on gestational days 11-21. Total RNA from the liver samples which collected from the offspring mice of postnatal day 7 and 21 was subjected to RNA sequencing. Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis were conducted to identify the functions of differentially expressed genes (DEGs). Four genes were selected for further validation by quantitative reverse transcription polymerase chain reaction (qRT-PCR). A total of 448 DEGs and 186 DEGs were identified on postnatal day 7 and 21, respectively. GO analysis revealed that the DEGs on postnatal day 7 mainly participated in the biological functions of cell growth and proliferation, and the DEGs on postnatal day 21 mainly participated in ion transport/activity. KEGG enrichment analysis showed that the DEGs on postnatal day 7 were mainly enriched in the cell cycle, cytokine-cytokine receptor interactions, hypertrophic cardiomyopathy, and the p53 signaling pathway, while the DEGs on postnatal day 21 were mainly enriched in neuroactive ligand-receptor interactions, the calcium signaling pathway, retinol metabolism, and axon guidance. The qRT-PCR results were consistent with the RNA sequencing data. The DEGs may affect the growth of liver in early postnatal period while may affect ion transport/activity in late postnatal period.

Pyroptosis is involved in maternal nicotine exposure-induced metabolic associated fatty liver disease progression in offspring mice.

We have investigated whether inflammasomes and pyroptosis are activated in maternal nicotine exposure (MNE) offspring mice and whether they are involved in MNE-promoted metabolic associated fatty liver disease (MAFLD) in adult offspring. We injected pregnant mice subcutaneously with saline vehicle or nicotine twice a day on gestational days 11-21. Offspring mice from both groups were fed with a normal diet (ND) or a high-fat diet (HFD) for 6 months at postnatal day 21 to develop the MAFLD model. Serum biochemical indices were analyzed, and liver histology was performed. The expression levels of inflammasome and pyroptosis proteins were detected by western blot. We found MNE significantly aggravated the injury of MAFLD in adult offspring mice. MNE activated inflammasomes and pyroptosis in both infant and adult offspring mice. HFD treatment activated inflammasomes but not pyroptosis at 3 months, while it showed no effect at 6 months. However, pyroptosis was more severe in MNE-HFD mice than in MNE-ND mice at 6 months. Taken together, our data suggest MNE promotes MAFLD progression in adult offspring mice. MNE also induces NLRP3 and NLRP6 inflammasome activation and pyroptosis in both infant and adult offspring mice, which may be involved in MNE-promoted progression of MAFLD.

Cortical Reorganization After Optical Alignment in Strabismic Patients Outside of Critical Period.

Purpose: To measure visual crowding, an essential bottleneck on object recognition and reliable psychophysical index of cortex organization, in older children and adults with horizontal concomitant strabismus before and after strabismus surgery. Methods: Using real-time eye tracking to ensure gaze-contingent display, we examined the peripheral visual crowding effects in older children and adults with horizontal concomitant strabismus but without amblyopia before and after strabismus surgery. Patients were asked to discriminate the orientation of the central tumbling E target letter with flankers arranged along the radial or tangential axis in the nasal or temporal hemifield at different eccentricities (5° or 10°). The critical spacing value, which is the minimum space between the target and the flankers required for correct discrimination, was obtained for comparisons before and after strabismus surgery. Results: Twelve individuals with exotropia (6 males, 21.75 ± 7.29 years, mean ± SD) and 15 individuals with esotropia (6 males, 24.13 ± 5.96 years) participated in this study. We found that strabismic individuals showed significantly larger critical spacing with nasotemporal asymmetry along the radial axis that related to the strabismus pattern, with exotropes exhibiting stronger temporal field crowding and esotropes exhibiting stronger nasal field crowding before surgical alignment. After surgery, the critical spacing was reduced and rebalanced between the nasal and temporal hemifields. Furthermore, the postoperative recovery of stereopsis was associated with the extent of nasotemporal balance of critical spacing. Conclusions: We find that optical realignment (i.e., strabismus surgery) can normalize the enlarged visual crowding effects, a reliable psychophysical index of cortical organization, in the peripheral visual field of older children and adults with strabismus and rebalance the nasotemporal asymmetry of crowding, promoting the recovery of postoperative stereopsis. Our results indicated a potential of experience-dependent cortical organization after axial alignment even for individuals who are out of the critical period of visual development, illuminating the capacity and limitations of optics on sensory plasticity and emphasizing the importance of ocular correction for clinical practice.

Visual Crowding Reveals Field- and Axis-Specific Cortical Miswiring After Long-Term Axial Misalignment in Strabismic Patients Without Amblyopia.

Purpose: Inspired by physiological and neuroimaging findings that revealed squint-induced modification of cortical volume and visual receptive field in early visual areas, we hypothesized that strabismic eyes without amblyopia manifest an increase in critical spacing of visual crowding, an essential bottleneck on object recognition and reliable psychophysical index of cortical organization. Methods: We used real-time eye tracking to ensure gaze-contingent display and examined visual crowding in patients with horizontal concomitant strabismus (both esotropia and exotropia) but without amblyopia and age-matched normal controls. Results: Nineteen patients with exotropia (12 men, mean ± SD = 22.89 ± 7.82 years), 21 patients with esotropia (10 men, mean ± SD = 23.48 ± 6.95 years), and 14 age-matched normal controls (7 men, mean ± SD = 23.07 ± 1.07 years) participated in this study. We found that patients with strabismus without amblyopia showed significantly larger critical spacing with nasotemporal asymmetry in only the radial axis that related to the strabismus pattern, with exotropia exhibiting stronger temporal hemifield crowding and esotropia exhibiting stronger nasal hemifield crowding, in both the deviated and fixating eyes. Moreover, the magnitude of crowding change was related to the duration and degree of strabismic deviation. Conclusions: Using visual crowding as a psychophysical index of cortical organization, our study demonstrated significantly greater peripheral visual crowding with nasotemporal asymmetry in only the radial axis in patients with strabismus without amblyopia, indicating the existence of hemifield- and axis-specific miswiring of cortical processing in object recognition induced by long-term adaptation to ocular misalignment.

Psychophysical Reverse Correlation Revealed Broader Orientation Tuning and Prolonged Reaction Time in Amblyopia.

Purpose: Neural selectivity of orientation is a fundamental property of visual system. We aim to investigate whether and how the orientation selectivity changes in amblyopia. Methods: Seventeen patients with amblyopia (27.1 ± 7.1 years) and 18 healthy participants (25.1 ± 2.7 years) took part in this study. They were asked to continuously detect vertical gratings embedded in a stream of randomly oriented gratings. Using a technique of subspace reverse correlation, the orientation-time perceptive field (PF) for the atypical grating detection task was derived for each participant. Detailed comparisons were made between the PFs measured with the amblyopic and healthy eyes. Results: The PF of the amblyopic eyes showed significant differences in orientation and time domain compared with that of the normal eyes (cluster-based permutation test, ps < 0.05), with broader bandwidth of orientation tuning (31.41 ± 10.59 degrees [mean ± SD] vs. 24.76 ± 6.85 degrees, P = 0.039) and delayed temporal dynamics (483 ± 68 ms vs. 425 ± 58 ms, P = 0.015). None of the altered PF properties correlated with the contrast sensitivity at 1 cycle per degree (c/deg) in amblyopia. No difference in PFs between the dominant and non-dominant eyes in the healthy group was found. Conclusions: The altered orientation-time PF to the low spatial frequency and high contrast stimuli suggests amblyopes had coarser orientation selectivity and prolonged reaction time. The broader orientation tuning probably reflects the abnormal lateral interaction in the primary visual cortex, whereas the temporal delay might indicate a high level deficit.

Identifying Long- and Short-Term Processes in Perceptual Learning.

Practice makes perfect in almost all perceptual tasks, but how perceptual improvements accumulate remains unknown. Here, we developed a multicomponent theoretical framework to model contributions of both long- and short-term processes in perceptual learning. Applications of the framework to the block-by-block learning curves of 49 adult participants in seven perceptual tasks identified ubiquitous long-term general learning and within-session relearning in most tasks. More importantly, we also found between-session forgetting in the vernier-offset discrimination, face-view discrimination, and auditory-frequency discrimination tasks; between-session off-line gain in the visual shape search task; and within-session adaptation and both between-session forgetting and off-line gain in the contrast detection task. The main results of the vernier-offset discrimination and visual shape search tasks were replicated in a new experiment. The multicomponent model provides a theoretical framework to identify component processes in perceptual learning and a potential tool to optimize learning in normal and clinical populations.

Maternal nicotine exposure aggravates metabolic associated fatty liver disease via PI3K/Akt signaling in adult offspring mice.

AIM: The aim of this study is to investigate the effect of maternal nicotine exposure (MNE) on the development of metabolic associated fatty liver disease (MAFLD) in adulthood offspring and the underlying mechanism. METHODS: Pregnant mice (n = 22) were subcutaneously injected with either saline vehicle (n = 11) or nicotine (n = 11) twice a day on gestational days 11-21. Offspring mice (n = 176) from both groups were weaned at postnatal day 21, and for 6 months after postnatal day 21, 96 mice were fed either a standard chow diet (n = 48) or a high-fat diet (n = 48). Serum lipid indicators, liver function indicators, insulin, and liver mitochondrial respiration were analyzed. The expression levels of fibrosis-related proteins, phosphorylated PI3K, phosphorylated Akt, sterol regulatory element-binding transcription factor 1 (SREBP1c), and peroxisome proliferator-activated receptor alpha (PPAR-α) were detected in the liver by immunohistochemistry and Western blotting. RESULTS: MNE significantly decreased the weight of both maternal and offspring mice (~30%) and inhibited organ growth in offspring mice (P < .05). MNE also significantly increased serum levels of total bile acid, triglycerides, total cholesterol, glucose, alanine aminotransferase, aspartate aminotransferase, low-density lipoprotein, and insulin while decreasing serum high-density lipoprotein levels and mitochondrial respiration activity in mice fed either the normal diet or high-fat diet (all P < .05). These effects of MNE on lipid metabolism and insulin resistance were mediated via PI3K and Akt phosphorylation and down-regulation of SREBP1c and PPAR-α. CONCLUSION: Our data indicate MNE induces lipid metabolism disorder and insulin resistance to promote MAFLD progression in adult offspring through activation of PI3K/Akt signaling and suppression of SREBP1c and PPARα protein expression.

Effect of physiological aging on binocular vision.

We see the world with two eyes. Binocular vision provides more ample information through interocular interaction. Previous studies have shown that aging impairs a variety of visual functions, but how aging affects binocular vision is still unclear. In this study, we measured three typical binocular functions-binocular combination, binocular rivalry, and stereo vision-to investigate aging-related effects on binocular vision in a relatively large sample (48 younger adults and 27 older adults) with normal or corrected-to-normal distance vision and no ophthalmological and mental diseases. We found that there were no consistent aging-related declines in binocular vision, with the worst effect on alternation frequency in binocular rivalry and no effect on binocular phase combination and stereo vision tested by Titmus. In addition, aging changed the correlation pattern among some of these binocular functions. These results reflected (at least partially) different aging-related mechanism(s) in binocular vision.

Comparison of the binding characteristics of SARS-CoV and SARS-CoV-2 RBDs to ACE2 at different temperatures by MD simulations.

Temperature plays a significant role in the survival and transmission of SARS-CoV (severe acute respiratory syndrome coronavirus) and SARS-CoV-2. To reveal the binding differences of SARS-CoV and SARS-CoV-2 receptor-binding domains (RBDs) to angiotensin-converting enzyme 2 (ACE2) at different temperatures at atomic level, 20 molecular dynamics simulations were carried out for SARS-CoV and SARS-CoV-2 RBD-ACE2 complexes at five selected temperatures, i.e. 200, 250, 273, 300 and 350 K. The analyses on structural flexibility and conformational distribution indicated that the structure of the SARS-CoV-2 RBD was more stable than that of the SARS-CoV RBD at all investigated temperatures. Then, molecular mechanics Poisson-Boltzmann surface area and solvated interaction energy approaches were combined to estimate the differences in binding affinity of SARS-CoV and SARS-CoV-2 RBDs to ACE2; it is found that the binding ability of ACE2 to the SARS-CoV-2 RBD was stronger than that to the SARS-CoV RBD at five temperatures, and the main reason for promoting such binding differences is electrostatic and polar interactions between RBDs and ACE2. Finally, the hotspot residues facilitating the binding of SARS-CoV and SARS-CoV-2 RBDs to ACE2, the key differential residues contributing to the difference in binding and the interaction mechanism of differential residues that exist at all investigated temperatures were analyzed and compared in depth. The current work would provide a molecular basis for better understanding of the high infectiousness of SARS-CoV-2 and offer better theoretical guidance for the design of inhibitors targeting infectious diseases caused by SARS-CoV-2.

The effects of short-term light exposure on subjective affect and comfort are dependent on the lighting time of day.

Light, one of the key environmental components for both life and work, played significant role in subjective feelings (e.g. affect and comfort), but the exact effects and mechanisms were still to be determined. The present study screened thirty healthy adults (13 females, 22.45 ± 3.26 years) and examined subjective affect and comfort under short-term white lights with different combination of correlated color temperature (CCT) and illuminance at different times of day (e.g. morning, afternoon, and evening). Our results showed a significant interaction between illuminance level and time-of-day on subjective comfort. Participants felt more comfortable under 50 lx and 100 lx instead of 500 lx in the evening, and more comfortable under 500 lx in the morning and afternoon. In addition, a positive correlation between illuminance and comfort in the morning and a negative correlation between them in the evening were found. No significant effect of CCT on any subjective feeling was revealed. Our results necessitate the consideration of time-of-day in understanding lighting effects and application of healthy lighting in daily life.

Coexistence of ovarian serous papillary cystadenofibroma and type A insulin resistance syndrome in a 14-year-old girl: A case report.

BACKGROUND: Type A insulin resistance syndrome is a rare disorder caused by mutations in the gene encoding the insulin receptor. Its coexistence with ovarian serous papillary cystadenofibroma is even rarer. CASE SUMMARY: A 14-year-old girl developed type A insulin resistance syndrome and showed high fasting insulin, glucose, and hemoglobin A1c (HbA1c) levels. The girl suffered from ovarian serous papillary cystadenofibroma. The laboratory results were as follows: fasting insulin was 2624.90 pmol/L and HbA1c was 8.5%. A heterozygous missense mutation on exon 20 of the insulin receptor gene (c.3601C>T, Arg1201Trp) was observed. The histopathological diagnosis was a cystic lesion that extended to the upper right uterus, indicating a right ovarian serous papillary cystadefibroma accompanied by focal interstitial hyperplasia. The patient was treated with metformin for over 6 mo. Additionally, laparoscopic resection (bilateral) of the ovarian lesion and laparoscopic intestinal adhesiolysis were performed under general anesthesia. Diet therapy combined with exercise was then initiated. The patient had an uneventful recovery. The patient also showed improved blood glucose control, with reduced levels of fasting insulin (857.84 pmol/L) and HbA1c (7.0%). CONCLUSION: Insulin resistance may play a significant role in the induction of tumors. It is important to investigate further the association between insulin resistance and tumors and the underlying mechanism.

General learning ability in perceptual learning.

Developing expertise in any field usually requires acquisition of a wide range of skills. Most current studies on perceptual learning have focused on a single task and concluded that learning is quite specific to the trained task, and the ubiquitous individual differences reflect random fluctuations across subjects. Whether there exists a general learning ability that determines individual learning performance across multiple tasks remains largely unknown. In a large-scale perceptual learning study with a wide range of training tasks, we found that initial performance, task, and individual differences all contributed significantly to the learning rates across the tasks. Most importantly, we were able to extract both a task-specific but subject-invariant component of learning, that accounted for 38.6% of the variance, and a subject-specific but task-invariant perceptual learning ability, that accounted for 36.8% of the variance. The existence of a general perceptual learning ability across multiple tasks suggests that individual differences in perceptual learning are not "noise"; rather, they reflect the variability of learning ability across individuals. These results could have important implications for selecting potential trainees in occupations that require perceptual expertise and designing better training protocols to improve the efficiency of clinical rehabilitation.

Aging affects gain and internal noise in the visual system.

Visual functions decline with age, but how aging degrades visual functions remains controversial. In the current study, the mechanisms underlying age-related visual declines were examined psychophysically. We developed an efficient method to quickly explore contrast sensitivity as a function of nine spatial frequencies at three levels of external noise in both young and old subjects. Fifty-two young and twenty-six old subjects have been screened for ophthalmological and mental diseases and participated in the experiment. Contrast sensitivity varied significantly with spatial frequency, age, and level of external noise. By adopting a nonlinear observer model, we decomposed contrast sensitivity into inefficiencies in internal additive noise, internal multiplicative noise, perceptual template gain, and/or system non-linearity. Model analysis revealed that aging impacts both internal additive noise and perceptual template gain, and such age-related degradation is tuned to spatial frequency, which is also a good predictor to discriminate old from young. The quick characterization of contrast sensitivity functions at different noise levels and the accompanying analysis developed in the current study may have profound application in other clinical populations.

Efficacy of Vildagliptin Added to Continuous Subcutaneous Insulin Infusion (CSII) in Hospitalized Patients with Type 2 Diabetes.

INTRODUCTION: The aim of this study was to compare the efficacy of vildagliptin as add-on therapy to short-term continuous subcutaneous insulin infusion (CSII) with CSII monotherapy in hospitalized patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 200 hospitalized patients with inadequately controlled T2DM were randomized into groups, with one group receiving CSII monotherapy (CSII group, n =100) and the other group receiving CSII plus vildagliptin as add-on (CSII + Vig group, n = 100). Of these, 191 completed the 7-day trial (CSII group, n = 99; CSII + Vig group, n = 92) and included in the analysis. The glycemic control and variability of the patients were measured using all-day capillary blood glucose (BG) monitoring. Weight and fasting C-peptide levels were evaluated before and after the interventions. RESULTS: Mean BG concentrations during the whole treatment period were lower and the time to reach target BG was reduced in the CSII + Vig group compared with the CSII group (9.89 ± 3.37 vs. 9.46 ± 3.23 mmol/L, P < 0.01; 129 ± 4 vs. 94 ± 5 h, P < 0.01, respectively). Similarly, the indicators of glycemic variability, namely the standard deviation of BG and the largest amplitude of glycemic excursion, were significantly decreased in the CSII + Vig group compared with the CSII group (2.68 ± 1.05 vs. 2.39 ± 1.00 mmol/L, P < 0.01; 7.19 ± 2.86 vs. 6.23 ± 2.73 mmol/L, P < 0.01, respectively). CONCLUSIONS: Short-term CSII with vildagliptin as add-on therapy may be an optimized treatment for hospitalized patients with T2DM compared with short-term CSII monotherapy.

Effects of Prepregnancy Body Mass Index, Weight Gain, and Gestational Diabetes Mellitus on Pregnancy Outcomes: A Population-Based Study in Xiamen, China, 2011-2018.

BACKGROUND: It is unclear that how prepregnancy body mass index (BMI), gestational weight gain (GWG), and gestational diabetes mellitus (GDM) affect pregnancy outcomes in -China. Thus, we explored how BMI, GWG, and GDM affect the risks of adverse pregnancy outcomes. METHODS: We performed a retrospective, population-based study included all births in Xiamen, China, 2011-2018. Demographic data and pregnancy outcomes of 73,498 women were acquired from the Medical Birth Registry of Xiamen. Women were categorized into groups on prepregnancy BMI and GWG in order to assess the risk of pregnancy outcomes. Multivariable logistic regression was performed to evaluate risk factors. RESULTS: Overall, 6,982 (9.37%) women were obese, and 8,874 (12.07%) women were overweight. Obese women are more vulnerable to cesarean delivery, preterm birth, large-for-gestational age (LGA), and macrosomia (crude OR [cOR] 2.00, 1.89-2.12; 1.35, 1.20-1.51; 2.12, 1.99-2.26; 2.53, 2.25-2.86, respectively, adjusted ORs 1.73, 1.62-1.84; 1.25, 1.10-1.42; 2.03, 1.90-2.18; 2.77, 2.44-3.16, respectively). Similar results were observed in overweight women (cORs 1.49, 1.42-1.57; 1.02, 0.91-1.15; 1.60, 1.50-1.70; 2.01, 1.78-2.26, respectively). Furthermore, women who gain weight in excessive group were 1.43, 2.06, and 2.16 times to deliver cesarean, LGA, and macrosomia, respectively. Additionally, GDM women were easily subjected to cesarean section, preterm birth, LGA, low birth weight, and macrosamia (cORs 1.52, 1.55, 1.52, 1.37, 1.27, respectively). CONCLUSIONS: Obesity prior to pregnancy, excessive GWG, and GDM were all associated with increased odds of cesarean, LGA, and macrosomia. Blood glucose and weight control before and during pregnancy are needed that may reduce the complications of pregnancy.

Author Correction: Efficient Characterization and Classification of Contrast Sensitivity Functions in Aging.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

No effects of anodal transcranial direct current stimulation on contrast sensitivity function.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a well-established non-invasive brain stimulation technique that has been widely applied to modulate cortical excitability in human brain. The results of previous tDCS studies on modulating contrast sensitivity, one of the most fundamental visual functions, were mixed. OBJECTIVE: We aim to systematically investigate the effects of anodal tDCS on contrast sensitivity functions (CSF), evaluate the responsiveness explanation of tDCS effects, and discuss results along with measurement precision. METHODS: We designed a single-blinded, sham-controlled within-subject study. Twenty-seven healthy adult subjects received three sets of 15 min tDCS (two 2-mA anodal and one sham) that delivered at Oz, with CSF measured before and after each tDCS stimulation. Experimental sessions were separated by at least twenty-four hours. CSF was assessed with a Bayesian procedure that accurately estimated CSF within minutes. The anodal tDCS-induced effect was gauged with the change in CSF after stimulation; responsiveness was indexed by correlation between CSF changes in different stimulation; precision was calculated from resampling. RESULTS: Our results indicated that neither the first nor the second session anodal tDCS altered the CSF significantly. Responsiveness was inconsistent between the two anodal sessions, indicating the usual responder/non-responder explanation of tDCS effects was unconvincing. Precision was less than 2 dB and constant throughout the whole experiment. CONCLUSIONS: The anodal tDCS, at least with two sessions, has no effect on modulating CSF. The absence of anodal tDCS effect on CSF was not due to subject's responsiveness to tDCS or measurement precision. More studies were needed to determine the optimal vision modulation configuration.

In Situ Electrospinning Iodine-Based Fibrous Meshes for Antibacterial Wound Dressing.

For effective application of electrospinning and electrospun fibrous meshes in wound dressing, we have in situ electrospun poly(vinyl pyrrolidone)/iodine (PVP/I), PVP/poly(vinyl pyrrolidone)-iodine (PVPI) complex, and poly(vinyl butyral) (PVB)/PVPI solutions into fibrous membranes by a handheld electrospinning apparatus. The morphologies of the electrospun fibers were examined by SEM, and the hydrophobicity, gas permeability, and antibacterial properties of the as-spun meshes were also investigated. The flexibility and feasibility of in situ electrospinning PVP/I, PVP/PVPI, and PVB/PVPI membranes, as well as the excellent gas permeabilities and antibacterial properties of the as-spun meshes, promised their potential applications in wound healing.