Surgeon Upper Extremity Kinematics During Error and Error-Free Retropubic Trocar Passage.

INTRODUCTION AND HYPOTHESIS: Surgeon kinematics play a significant role in the prevention of patient injury. We hypothesized that elbow extension and ulnar wrist deviation are associated with bladder injury during simulated midurethral sling (MUS) procedures. METHODS: We used motion capture technology to measure surgeons' flexion/extension, abduction/adduction, and internal/external rotation angular time series for shoulder, elbow, and wrist joints. Starting and ending angles, minimum and maximum angles, and range of motion (ROM) were extracted from each time series. We created anatomical multibody models and applied linear mixed modeling to compare kinematics between trials with versus without bladder penetration and attending versus resident surgeons. A total of 32 trials would provide 90% power to detect a difference. RESULTS: Out of 85 passes, 62 were posterior to the suprapubic bone and 20 penetrated the bladder. Trials with versus without bladder penetration were associated with more initial wrist dorsiflexion (-27.32 vs -9.03°, p = 0.01), less final elbow flexion (39.49 vs 60.81, p = 0.03), and greater ROM in both the wrist (27.48 vs 14.01, p = 0.02), and elbow (20.45 vs 12.87, p = 0.04). Wrist deviation and arm pronation were not associated with bladder penetration. Compared with attendings, residents had more ROM in elbow flexion (14.61 vs 8.35°, p < 0.01), but less ROM in wrist dorsiflexion (13.31 vs 20.33, p = 0.02) and arm pronation (4.75 vs 38.46, p < 0.01). CONCLUSIONS: Bladder penetration during MUS is associated with wrist dorsiflexion and elbow flexion but not internal wrist deviation and arm supination. Attending surgeons exerted control with the wrist and forearm, surgical trainees with the elbow. Our findings have direct implications for MUS teaching.

Bioinductive Patch as an Augmentation for Rotator Cuff Repair, a Systematic Review and Meta-Analysis.

INTRODUCTION: Rotator cuff tears (RCTs) are a prevalent cause of shoulder pain and dysfunction. For those who fail initial conservative treatment, operative intervention can be pursued. A significant and common complication after rotator cuff repair (RCR) is retearing or non-healing. Numerous augmentations to traditional suture RCR have been studied. Of these, the Smith+Nephew Regeneten bioinductive collagen patch has had promising initial results; however, analytic data for its use is lacking, and there is no meta-analysis comparing the available data to historical RCR outcomes. METHODS: A PRISMA-guided literature search was conducted using Ovid MEDLINE, PubMED, Cochrane, and ClinicalTrials.gov. 13 studies met inclusion and exclusion criteria. Only clinical trials on full and partial-thickness tears were included. American Shoulder and Elbow Surgeon score (ASES), Constant-Murley score (CMS), the visual analog scale for pain (VAS), the minimal clinically important difference (MCID), tendon thickness, and complication rates were primary outcomes of interest. A meta-analysis was performed to determine the overall complication and retear rate from the included studies. RESULTS: ASES, CMS, and VAS improved significantly in all studies that reported them, and most patients achieved MCID. Patient-reported outcome measure (PROM) improvements were similar to historical improvements in standard RCR, and a similar proportion of patients achieved MCID after standard repair. Tendon thickness improved significantly and to a similar degree as standard RCR. Overall retear rate after full thickness RCR augmented with the bioinductive patch was 8.3%. For partial thickness RCR, total retear rate of 1.1% across all patients. The overall complication rate with the bioinductive patch was 15.5% across all full-thickness RCR studies and 16.2% in partial thickness RCR. We found overall retear rate to be lower after augmentation with the bioinductive patch compared to traditional repair; however, the overall complication rate was similar for full-thickness tears and higher for partial-thickness tears. Lastly, adverse reactions to the bioinductive patch were noted at 0.2%. CONCLUSIONS: The bioinductive collagen patch appears to be a safe augmentation for rotator cuff repair. Patients are likely to experience significant subjective improvement in PROMs and significant increases in tendon thickness. Retear rate has been a concern after RCR for decades, and the bioinductive patch may help mitigate this risk. There is a lack of case-control studies comparing the bioinductive patch to traditional suture RCR. Such data is needed to better determine the role of the bioinductive patch in the treatment of full and partial-thickness rotator cuff repairs.

Clinical efficacy of cyclosporin and natamycin for fungal keratitis.

Objectives: To investigate the clinical efficacy of cyclosporin (CYSP) and natamycin (NAT) as a combination therapy in patients with fungal keratitis. Methods: This is a retrospective study. A total of 64 patients (64 eyes) with fungal keratitis treated by Baoding No.1 Central Hospital between December 2018 and May 2022 according to their treatment methods were divided into a monotherapy (MT) group receiving NAT eye drops solely and a combination therapy (CT) group given CYSP eye drops in addition to the exact treatment provided for the MT group. The clinical responses, visual acuity changes, severity of eye symptoms, and adverse reactions were compared between the two groups. Results: At two and four weeks post-treatment, the CT group had an overall response rate (ORR) significantly higher than that of the MT group (P< 0.05, respectively); both groups showed improved visual acuity and eye symptoms compared with the pre-treatment condition, and these improvements were more pronounced in the CT group (P < 0.05, respectively). Compared with the MT group, the CT group experienced a significantly shorter duration of eye symptoms (P < 0.05). The adverse reaction rate(ARR) was 9.38% in the CT group and 6.25% in the MT group, and the difference was not significant (P > 0.05). Conclusion: Using CYSP and NAT as a combination therapy for fungal keratitis can substantially heighten the therapeutic effects, promote visual acuity recovery, and induce rapid remission of eye symptoms without increasing the risk of adverse reactions.

Snapshot: a package for clustering and visualizing epigenetic history during cell differentiation.

BACKGROUND: Epigenetic modification of chromatin plays a pivotal role in regulating gene expression during cell differentiation. The scale and complexity of epigenetic data pose significant challenges for biologists to identify the regulatory events controlling cell differentiation. RESULTS: To reduce the complexity, we developed a package, called Snapshot, for clustering and visualizing candidate cis-regulatory elements (cCREs) based on their epigenetic signals during cell differentiation. This package first introduces a binarized indexing strategy for clustering the cCREs. It then provides a series of easily interpretable figures for visualizing the signal and epigenetic state patterns of the cCREs clusters during the cell differentiation. It can also use different hierarchies of cell types to highlight the epigenetic history specific to any particular cell lineage. We demonstrate the utility of Snapshot using data from a consortium project for ValIdated Systematic IntegratiON (VISION) of epigenomic data in hematopoiesis. CONCLUSION: The package Snapshot can identify all distinct clusters of genomic locations with unique epigenetic signal patterns during cell differentiation. It outperforms other methods in terms of interpreting and reproducing the identified cCREs clusters. The package of Snapshot is available at GitHub: https://github.com/guanjue/Snapshot .

An integrative view of the regulatory and transcriptional landscapes in mouse hematopoiesis.

Thousands of epigenomic data sets have been generated in the past decade, but it is difficult for researchers to effectively use all the data relevant to their projects. Systematic integrative analysis can help meet this need, and the VISION project was established for validated systematic integration of epigenomic data in hematopoiesis. Here, we systematically integrated extensive data recording epigenetic features and transcriptomes from many sources, including individual laboratories and consortia, to produce a comprehensive view of the regulatory landscape of differentiating hematopoietic cell types in mouse. By using IDEAS as our integrative and discriminative epigenome annotation system, we identified and assigned epigenetic states simultaneously along chromosomes and across cell types, precisely and comprehensively. Combining nuclease accessibility and epigenetic states produced a set of more than 200,000 candidate cis-regulatory elements (cCREs) that efficiently capture enhancers and promoters. The transitions in epigenetic states of these cCREs across cell types provided insights into mechanisms of regulation, including decreases in numbers of active cCREs during differentiation of most lineages, transitions from poised to active or inactive states, and shifts in nuclease accessibility of CTCF-bound elements. Regression modeling of epigenetic states at cCREs and gene expression produced a versatile resource to improve selection of cCREs potentially regulating target genes. These resources are available from our VISION website to aid research in genomics and hematopoiesis.

General Synthesis of N-CF3 Heteroaryl Amides via Successive Fluorination and Acylation of Sterically Hindered Isothiocyanates.

We report the one-pot synthesis of N-CF3 heteroaryl amides (NTFMHA) from heteroaryl carboxylic acids and sterically hindered isothiocyanates, including various amino acid analogues, in the presence of AgF. The key to this reaction is the utilization of free heteroaryl acyl chlorides, rather than their corresponding hydrochloride salts. This method represents a complementary method of our previous work and enables modification to a variety of previously inaccessible structures, including α-tertiary amines and N-CF3-modified pharmaceuticals.

Unraveling the Marked Differences of the Excited-State Properties of Arylgold(III) Complexes with C∧N∧C Tridentate Ligands.

Three structurally similar gold(III) complexes with C∧N∧C tridentate ligands, [1; C∧N∧C = 2,6-diphenylpyridine], [2; C∧N∧C = 2,6-diphenylpyrazine], and [3; C∧N∧C = 2,6-diphenyltriazine], have been investigated theoretically to rationalize the marked difference in emission behaviors. The geometrical and electronic structures, spectra properties, radiative and nonradiative decay processes, as well as reverse intersystem crossing and reverse internal conversion (RIC) processes were thoroughly analyzed using density functional theory (DFT) and time-dependent DFT calculations. The computed results indicate that there is a small energy difference ΔET1-T1' between the lowest-energy triplet state (T1) and the second lowest-energy triplet state (T1') of complexes 2 and 3, suggesting that the excitons in the T1 state can reach the emissive higher-energy T1' through the RIC process. In addition, the non-emissive T1 states of gold(III) complexes in solution can be ascribed to the easily accessible metal-centered (3MC) state or possibly tunneling into high-energy vibrationally excited singlet states for nonradiative decay. The low efficiency of 3 is attributed to the deactivation pathway via the 3MC state. The present study elucidates the relationship between structure and property of gold(III) complexes featuring C∧N∧C ligands and providing a comprehensive understanding of the significant differences in their luminescence behaviors.

TsOH-catalyzed acyl migration reaction of the Bz-group: innovative assembly of various building blocks for the synthesis of saccharides.

We developed an efficient method to achieve the regioselective acyl migration of benzoyl ester. In all the cases, the reactions required only the commercially available organic acid catalyst TsOH·H2O. This method enables the benzoyl group to migrate from secondary groups to primary hydroxyl groups, or from equatorial secondary hydroxyl groups to axial hydroxyl groups. The 1,2 or 1,3 acyl migration would potentially occur via five- and six-membered cyclic ortho acid intermediates. A wide range of orthogonally protected monosaccharides, which are useful intermediates for the synthesis of natural oligosaccharides, were synthesized. Finally, to demonstrate the utility of the method, a tetrasaccharide portion from a mycobacterial cell wall polysaccharide was assembled.

Decreased syntaxin17 expression contributes to the pathogenesis of acute pancreatitis in murine models by impairing autophagic degradation.

Acute pancreatitis (AP) is an inflammatory disease of the exocrine pancreas. Disruptions in organelle homeostasis, including macroautophagy/autophagy dysfunction and endoplasmic reticulum (ER) stress, have been implicated in human and rodent pancreatitis. Syntaxin 17 (STX17) belongs to the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) subfamily. The Qa-SNARE STX17 is an autophagosomal SNARE protein that interacts with SNAP29 (Qbc-SNARE) and the lysosomal SNARE VAMP8 (R-SNARE) to drive autophagosome-lysosome fusion. In this study, we investigated the role of STX17 in the pathogenesis of AP in male mice or rats induced by repeated intraperitoneal injections of cerulein. We showed that cerulein hyperstimulation induced AP in mouse and rat models, which was characterized by increased serum amylase and lipase activities, pancreatic edema, necrotic cell death and the infiltration of inflammatory cells, as well as markedly decreased pancreatic STX17 expression. A similar reduction in STX17 levels was observed in primary and AR42J pancreatic acinar cells treated with CCK (100 nM) in vitro. By analyzing autophagic flux, we found that the decrease in STX17 blocked autophagosome-lysosome fusion and autophagic degradation, as well as the activation of ER stress. Pancreas-specific STX17 knockdown using adenovirus-shSTX17 further exacerbated pancreatic edema, inflammatory cell infiltration and necrotic cell death after cerulein injection. These data demonstrate a critical role of STX17 in maintaining pancreatic homeostasis and provide new evidence that autophagy serves as a protective mechanism against AP.

Prevalence Patterns and Onset Prediction of High Myopia for Children and Adolescents in Southern China via Real-World Screening Data: Retrospective School-Based Study.

BACKGROUND: Patients with high myopia have an increased lifetime risk of complications. The prevalence patterns of high myopia in children and adolescents in southern China are unclear. Early identification of high-risk individuals is critical for reducing the occurrence and development of high myopia and avoiding the resulting complications. OBJECTIVE: This study aimed to determine the prevalence of high myopia in children and adolescents in southern China via real-world screening data and to predict its onset by studying the risk factors for high myopia based on machine learning. METHODS: This retrospective school-based study was conducted in 13 cities with different gross domestic products in southern China. Through data acquisition and filtering, we analyzed the prevalence of high myopia and its association with age, school stage, gross domestic product, and risk factors. A random forest algorithm was used to predict high myopia among schoolchildren and then assessed in an independent hold-out group. RESULTS: There were 1,285,609 participants (mean age 11.80, SD 3.07, range 6-20 years), of whom 658,516 (51.2%) were male. The overall prevalence of high myopia was 4.48% (2019), 4.88% (2020), and 3.17% (2021), with an increasing trend from the age of 11 to 17 years. The rates of high myopia increased from elementary schools to high schools but decreased at all school stages from 2019 to 2021. The coastal and southern cities had a higher proportion of high myopia, with an overall prevalence between 2.60% and 5.83%. Age, uncorrected distance visual acuity, and spherical equivalents were predictive factors for high myopia onset in schoolchildren. The random forest algorithm achieved a high accuracy of 0.948. The area under the receiver operator characteristic curve (AUC) was 0.975. Both indicated sufficient model efficacy. The performance of the model was validated in an external test with high accuracy (0.971) and a high AUC (0.957). CONCLUSIONS: High myopia had a high incidence in Guangdong Province. Its onset in children and adolescents was well predicted with the random forest algorithm. Efficient use of real-world data can contribute to the prevention and early diagnosis of high myopia.

Sleep among Obstetrics and Gynecology Trainees: Results from a Yoga-Based Wellness Initiative.

OBJECTIVE: This study aimed to determine the feasibility of using a wrist-based fitness tracking device to assess sleep among Obstetrics and Gynecology (OBGYN) trainees who engaged in a yoga-based wellness program. We also sought to evaluate the effects of yoga on sleep. STUDY DESIGN: A quality improvement initiative consisting of an 8-week wellness program of weekly yoga classes, nutrition, and physical challenges was implemented for OBGYN residents and Maternal-Fetal Medicine fellows. The Polar A370 fitness tracker device was provided and synced to the Polar Flow for Coach program for inclusion. Data obtained included total and restful sleep from each night the device were worn. Pre- and post-assessment of the Pittsburg Sleep Quality Index (PSQI) were compared. Linear mixed models were used to estimate and test the effect of yoga on sleep while controlling for on-call shifts. RESULTS: Of the 15 participants who synced their device, 13 (87%) were included for analysis. Sleep data from 572 nights were analyzed. The mean (SD) total sleep was 434.28 (110.03) minutes over the 8 weeks. A minimum of 7 hours (420 minutes) of total sleep occurred 59.3% of the time. After controlling for Friday or Saturday night on-call, those who attended yoga class had a significantly greater total sleep (yoga: 425.14 minutes [41.89], no yoga: 357.33 [43.04] minutes; p = 0.04). There was no significant change in the mean global PSQI score after the program (pre: 5.0 [1.6], post: 5.1 [2.5], p = 0.35). CONCLUSION: Wearable fitness monitors provide insight into sleep patterns displayed during training and can serve as a tool to identify those who are sleep deprived and assist in the evaluation of trainee wellness. Training programs are encouraged to provide access to yoga and mindfulness interventions to improve sleep and possibly clinical performance. KEY POINTS: · Yoga improves trainee sleep by approximately 60 minutes.. · Total and restful sleep are reduced during night float rotation.. · Trainees obtained 7 hours of sleep approximately 60% of the time..

Magnetic Resonance Imaging Combined with Histological Techniques for Dynamic Assessment of Cytotoxic Edema after Cerebral Ischemia-Reperfusion Injury.

BACKGROUND: Reperfusion therapy after ischemic cerebral stroke may cause cerebral ischemia-reperfusion injury (CIRI), and cerebral edema is an important factor that may aggravate CIRI. Our study aimed to dynamically monitor the development of early cytotoxic edema after CIRI by magnetic resonance imaging (MRI) and to validate it using multiple histological imaging methods. METHODS: Male Sprague Dawley rats were divided into sham and CIRI groups. T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI)-MRI scans were performed in the sham and CIRI groups after reperfusion. Relative apparent diffusion coefficient (rADC) values were calculated and the midline shift (MLS) was measured. A series of histological detection techniques were performed to observe changes in the cerebral cortex and striatum of CIRI rats. Correlation analysis of rADC values with aquaporin-4 (AQP4) and sodium-potassium-chloride cotransport protein 1 (Na+-K+-2Cl-- cotransporter 1; NKCC1) was performed. RESULTS: rADC values began to increase and reached a relatively low value in the cerebral cortex and striatum at 24 h after reperfusion, and the MLS reached relatively high values at 24 h after reperfusion (all p < 0.05). Hematoxylin-eosin (HE) staining showed that the nerve cells in the cortex and striatum of the sham group were regular in morphology and neatly arranged, and in the CIRI-24 h group were irregular, disorganized, and loosely structured. Using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, the number of TUNEL+ cells in the ischemic cortex and striatum in CIRI-24 h group was shown to increase significantly compared with the sham group (p < 0.05). Transmission electron microscopy showed that the perivascular astrocytic foot processes were swollen in the cortex and striatum of the CIRI-24 h group. Pearson correlation analysis demonstrated that rADC values were negatively correlated with the number of anti-glial fibrillary acidic protein (GFAP)+AQP4+ and GFAP+NKCC1+ cells of the CIRI rats. CONCLUSIONS: MRI combined with histological techniques can dynamically assess cytotoxic edema after CIRI, in a manner that is clear and intuitive for scientific researchers and clinicians, and provides a scientific basis for the application of MRI techniques for monitoring the dynamic progress of CIRI.

New Indole Diketopiperazine Alkaloids from Soft Coral-Associated Epiphytic Fungus Aspergillus versicolor CGF 9-1-2.

Two new indole diketopiperazine alkaloids (IDAs), (+)19-epi-sclerotiamide (1) and (-)19-epi-sclerotiamide (2), along with 13 known analogs (3-15), were isolated from a soft coral-associated epiphytic fungus Aspergillus versicolor CGF 9-1-2. The structures of two new compounds were established based on the combination of HR-ESI-MS, 1D and 2D NMR spectroscopy, optical rotation measurements and quantum chemical 13 C-NMR, the absolute configurations were determined by experimental and electronic circular dichroism (ECD) calculations. The results of molecular docking showed that all the compounds had a good binding with TDP1, TDP2, TOP1, TOP2, Ache, NLRP3, EGFR, EGFR L858R, EGFR T790M and EGFR T790/L858. Biological evaluation of compounds 3, 6, 8, 11 showed that 3 exerted a strong inhibitory effect on TDP2 with a rate of 81.72 %.

Decision-making in the treatment of radial head fractures: Delphi methodology.

BACKGROUND: The treatment of partially displaced radial head fractures is determined not only by the type of fracture but also by patient characteristics such as age, occupation, hand dominance, mechanism of injury, and concomitant injuries and comorbidities. The goal of this study was to employ the Delphi method to achieve consensus on the management of patients with radial head fractures, utilizing the experience of the ASES Elbow Fracture-Dislocation Multicenter Study Group and Mayo Elbow Club surgeons. METHODS: The initial survey was sent to participants, which included consent to participate in the study and questions about their experience, knowledge, and interest in participating in the Delphi method. We used both open-ended and category-based questions. The second questionnaire generated 76 variables, and individual questions with mean Likert ratings of <2.0 or >4.0 were deemed significant and merged to form multifactorial clinical scenarios relating to both nonoperative and operative management, respectively. RESULTS: Of the surgeons who responded to the questionnaire, 64% were from the United States, while the remainder were from overseas practices. Years in practice on average were 12.4 years (range, 1-40). Seven of the 76 factors met the criteria of a mean Likert score of <2.0 or >4.0. These factors were as follows: age, block to the range of motion (ROM) after aspiration/injection, crepitation with ROM, tenderness over the distal radioulnar joint and/or interosseous membrane (dorsal forearm), gap and/or displacement >2 mm on imaging, complete loss of contact of the head with the rest of the radius on imaging, and fracture head involvement 30% on imaging. Twenty-two (46%) of the 96 clinical scenarios gained >90% consensus in favor of surgical treatment, whereas 8 (17%) reached >90% consensus in favor of nonoperative treatment. CONCLUSION: Obtaining expert consensus on the treatment of radial head fractures remains challenging. Certain factors such as gap/displacement ≥2 mm without complete loss of contact, ≥30% head involvement with a block to an ROM regardless of tenderness over distal radioulnar joint or interosseous membrane (dorsal forearm), or crepitation when the patient was <80 years of age led to a recommendation of operative treatment in 100% of the surveyed surgeons. Patients older than 80 years with no block to ROM after aspiration/injection, no crepitation with ROM, and no tenderness on distal radioulnar joint/interosseous membrane (dorsal forearm) were recommended for nonoperative treatment regardless of the size of the radial head involvement on imaging.

Risk of Recall for Total Joint Arthroplasty Devices Over 10 Years.

BACKGROUND: Orthopaedic devices comprise nearly 20% of devices on the market and 12% to 20% of these devices undergo a recall within 10 years. More than 95% of these devices are approved without supporting clinical data through the Food and Drug Administration's 510(k) pathway. The risk of recall of orthopaedic arthroplasty devices approved through the 510(k) pathway has not been previously studied. METHODS: The FDA 510(k) database was queried for orthopaedic devices approved between January 01, 2008 and December 31, 2018 and subsequently codified to hip and knee arthroplasty devices using product codes. The database included 904 arthroplasty devices during the study period, with hip and knee making up 53.7% (485) and 46.3% (419) of devices, respectively. Information regarding numbers, dates, and reasons for recall were recorded. Cumulative incidence function was conducted to compare the risk of recall between hip and knee arthroplasty. RESULTS: In total, 94 (19.4%) hip and 85 (20.3%) knee devices were recalled. The hazard of recall by 10 years for hip and knee arthroplasty devices was approximately 24%, with no statistical differences between each region. The most common causes of recall were process control and device design, accounting for 29.6% and 26.3% of recalls, respectively, with no significant difference between study groups. CONCLUSION: The risk of recall for arthroplasty devices is more than that previously understood. Improved postmarket surveillance strategies along with increased physician participation in detecting and reporting device safety issues are necessary to strengthen patient safety.

Unravelling the Link between Psychological Distress and Liver Disease: Insights from an Anxiety-like Rat Model and Metabolomics Analysis.

Psychological distress is associated with an increase in liver disease mortality. This association highlights the close relationship between psychological and physical health. The underlying mechanism of this association needs to be elucidated. In this study, a rat model of anxiety was developed via compound stress. Changes in the HPA axis and inflammatory factors in the brains of the rats were evaluated for behavioral tests and liver function, respectively. The liver metabolic profiles of the rats were characterized through liquid chromatography-mass spectrometry (LC-MS). Differential metabolites were screened based on the conditions of p < 0.05 and VIP > 1. A pathway enrichment analysis was performed on the metabolomics data using the Ingenuity Pathway Analysis (IPA). Immunofluorescence (IF), immunohistochemistry (IHC), and Western blotting assays were performed to examine the expression of the screened target epidermal growth factor receptor (EGFR) and to elucidate the pathway associated with the mechanism. The results showed the impairment of liver function among the rats in an anxiety-like state. Additionally, 61 differential metabolites in the control and anxiety groups were screened using metabolomics (p < 0.05, VIP > 1). The results of the IPA analysis showed that the key target was EGFR. We also found that an anxiety-like state in rats may cause liver injury through the EFGR/PI3K/AKT/NF-κB pathway, which can lead to the production of inflammatory factors in the liver. Our results revealed a mechanism by which anxiety-like behavior leads to liver damage in rats. The findings of this study provided new insights into the deleterious effects of psychological problems on physical health.

The Effects of Early-Life Stress on Liver Transcriptomics and the Protective Role of EPA in a Mouse Model of Early-Life-Stress-Induced Adolescent Depression.

Early-life stress (ELS) was found to increase the risk of adolescent depression, and clinical evidence indicated that eicosapentaenoic acid (EPA) was decreased in patients with adolescent depression, but the underlying mechanisms are unclear. Here, we utilized an ELS model of maternal separation with early weaning to explore the protective role of EPA in adolescent depression. We found that that ELS induced depression-like behavior rather than anxiety-like behavior in adolescent mice. RNA-sequencing results showed that ELS changed the transcription pattern in the liver, including 863 upregulated genes and 971 downregulated genes, especially those related to the biosynthesis of unsaturated fatty acids metabolism in the liver. Moreover, ELS decreased the expression of the rate-limiting enzymes, fatty acid desaturases 1/2 (FADS1/2), involved in the biosynthesis of EPA in the liver. Additionally, ELS reduced the levels of EPA in the liver, serum, and hippocampus, and EPA administration improved depression-like behavior-induced by ELS. Our results provide transcriptomic evidence that ELS increases the risk of adolescent depression by reducing the synthesis of unsaturated fatty acids in the liver, especially EPA, and suggest that supplementation with EPA should be investigated as a potential treatment for adolescent depression.

Natamycin versus natamycin combined with voriconazole in the treatment of fungal keratitis.

Objective: To observe the therapeutic effect of natamycin combined with voriconazole in the treatment of fungal keratitis (FK). Methods: This is a retrospective study. The subjects of this study were 64 patients with FK who were admitted to Baoding No.1 Central Hospital from February 2019 to July 2022. The enrolled patients were divided into control group (n= 32) and study group (n= 32) by the random number table method. The control group was treated with natamycin alone, and the study group was treated with natamycin combined with voriconazole. The total efficacy, time of disappearance of ocular symptoms, visual acuity level, keratitis severity score, corneal ulcer area, tear fungus index and incidence of adverse reactions were compared between the two groups. Results: The total efficacy,of the study group was significantly higher than that of the control group. The disappearance time of corneal ulcer, photophobia, foreign body sensation and hypopyon in the study group was shorter than those in the control group. Keratitis severity score and (1,3)-ß-D-glucan level in the study group were lower than those in the control group. The corneal ulcer area was narrowed in the study group than that of the control group, and the visual acuity level in the former group was higher than that of the latter group. Besides, there was no significant difference in the frequency of adverse reactions between the two groups. Conclusion: Natamycin combined with voriconazole is safe and effective in the treatment of FK.

Genome-wide analysis of the CCT gene family in Chinese white pear (Pyrus bretschneideri Rehd.) and characterization of PbPRR2 in response to varying light signals.

BACKGROUND: Canopy architecture is critical in determining the light environment and subsequently the photosynthetic productivity of fruit crops. Numerous CCT domain-containing genes are crucial for plant adaptive responses to diverse environmental cues. Two CCT genes, the orthologues of AtPRR5 in pear, have been reported to be strongly correlated with photosynthetic performance under distinct canopy microclimates. However, knowledge concerning the specific expression patterns and roles of pear CCT family genes (PbCCTs) remains very limited. The key roles played by PbCCTs in the light response led us to examine this large gene family in more detail. RESULTS: Genome-wide sequence analysis identified 42 putative PbCCTs in the genome of pear (Pyrus bretschneideri Rehd.). Phylogenetic analysis indicated that these genes were divided into five subfamilies, namely, COL (14 members), PRR (8 members), ZIM (6 members), TCR1 (6 members) and ASML2 (8 members). Analysis of exon-intron structures and conserved domains provided support for the classification. Genome duplication analysis indicated that whole-genome duplication/segmental duplication events played a crucial role in the expansion of the CCT family in pear and that the CCT family evolved under the effect of purifying selection. Expression profiles exhibited diverse expression patterns of PbCCTs in various tissues and in response to varying light signals. Additionally, transient overexpression of PbPRR2 in tobacco leaves resulted in inhibition of photosynthetic performance, suggesting its possible involvement in the repression of photosynthesis. CONCLUSIONS: This study provides a comprehensive analysis of the CCT gene family in pear and will facilitate further functional investigations of PbCCTs to uncover their biological roles in the light response.

Impact of COVID-19 Restrictions on Stage of Breast Cancer at Presentation and Time to Treatment at an Urban Safety-Net Hospital.

BACKGROUND: COVID-19 disrupted health systems across the country. Pre-pandemic, patients accessing our urban safety-net hospital presented with three-fold higher rates of late-stage breast cancer than other Commission-on-Cancer sites. We sought to determine the effect of the COVID-19 pandemic on stage of breast cancer presentation and time to first treatment at our urban safety-net hospital. METHODS: An Institutional Review Board-approved cohort study of newly diagnosed breast cancer patients was conducted at our safety-net hospital comparing a COVID cohort (March 2020-February 2021, n = 82) with a pre-COVID cohort (March 2018-February 2019, n = 90). Demographic information, stage at presentation, and time to first treatment-subdivided into time from symptom to diagnosis and diagnosis to treatment-were collected and analyzed for effect of COVID pandemic. RESULTS: Cohorts were similar in age, race, and payor. More patients had late-stage disease during COVID (32%) than pre-COVID (19%, p = 0.05). There was a significantly longer time to first treatment during COVID (p = 0.0001) explained by a significantly longer time from symptom to diagnosis (p = 0.0001), with no difference in time from diagnosis to treatment. CONCLUSION: It was significantly more likely for patients to present to our safety-net hospital with late-stage breast cancer during COVID than pre-COVID. There was longer time to first treatment during COVID, driven by the increased time from symptom to diagnosis. Patients may have perceived that care was inaccessible during the pandemic or had competing priorities, driving delays. Efforts should be made to minimize disruption to safety-net hospitals during future shut-downs as these are among the most vulnerable patients.