Resolving the In Situ Three-Dimensional Structure of Fly Mechanosensory Organelles Using Serial Section Electron Tomography.

Mechanosensory organelles (MOs) are specialized subcellular entities where force-sensitive channels and supporting structures (e.g., microtubule cytoskeleton) are organized in an orderly manner. The delicate structure of MOs needs to be resolved to understand the mechanisms by which they detect forces and how they are formed. Here, we describe a protocol that allows obtaining detailed information about the nanoscopic ultrastructure of fly MOs by using serial section electron tomography (SS-ET). To preserve fine structural details, the tissues are cryo-immobilized using a high-pressure freezer followed by freeze-substitution at low temperature and embedding in resin at room temperature. Then, sample sections are prepared and used to acquire the dual-axis tilt series images, which are further processed for tomographic reconstruction. Finally, tomograms of consecutive sections are combined into a single larger volume using microtubules as fiducial markers. Using this protocol, we managed to reconstruct the sensory organelles, which provide novel molecular insights as to how fly mechanosensory organelles work and are formed. Based on our experience, we think that, with minimal modifications, this protocol can be adapted to a wide range of applications using different cell and tissue samples. Key features • Resolving the high-resolution 3D ultrastructure of subcellular organelles using serial section electron tomography (SS-ET). • Compared with single-axis tilt series, dual-axis tilt series provides a much wider coverage of Fourier space, improving resolution and features in the reconstructed tomograms. • The use of high-pressure freezing and freeze-substitution maximally preserves the fine structural details.

Association Between Electronic Diary-Rated Sleep, Mood, Energy, and Stress With Incident Headache in a Community-Based Sample.

BACKGROUND AND OBJECTIVES: The aim of this study was to examine the diurnal links between average and changes in average levels of prospectively rated mood, sleep, energy, and stress as predictors of incident headache in a community-based sample. METHODS: This observational study included structured clinical diagnostic assessment of both headache syndromes and mental disorders and electronic diaries that were administered 4 times per day for 2 weeks yielding a total of 4,974 assessments. The chief outcomes were incident morning (am) and later-day (pm) headaches. Generalized linear mixed-effects models were used to evaluate the average and lagged values of predictors including subjectively rated mood, anxiety, energy, stress, and sleep quality and objectively measured sleep duration and efficiency on incident am and pm headaches. RESULTS: The sample included 477 participants (61% female), aged 7 through 84 years. After adjusting for demographic and clinical covariates and emotional states, incident am headache was associated with lower average (ß = -0.206*; confidence intervals: -0.397 to -0.017) and a decrease in average sleep quality on the prior day (ß = -0.172*; confidence interval: -0.305, -0.039). Average stress and changes in subjective energy levels on the prior day were associated with incident headaches but with different valence for am (decrease) (ß = -0.145* confidence interval: -0.286, -0.005) and pm (increase) (ß = 0.157*; confidence interval: 0.032, 0.281) headache. Mood and anxiety disorders were not significantly associated with incident headache after controlling for history of a diagnosis of migraine. DISCUSSION: Both persistent and acute changes in arousal states manifest by subjective sleep quality and energy are salient precursors of incident headaches. Whereas poorer sleep quality and decreased energy on the prior day were associated with incident morning headache, an increase in energy and greater average stress were associated with headache onsets later in the day. Different patterns of predictors of morning and later-day incident headache highlight the role of circadian rhythms in the manifestations of headache. These findings may provide insight into the pathophysiologic processes underlying migraine and inform clinical intervention and prevention. Tracking these systems in real time with mobile technology provides a valuable ancillary tool to traditional clinical assessments.

Life-history stage determines the diet of ectoparasitic mites on their honey bee hosts.

Ectoparasitic mites of the genera Varroa and Tropilaelaps have evolved to exclusively exploit honey bees as food sources during alternating dispersal and reproductive life history stages. Here we show that the primary food source utilized by Varroa destructor depends on the host life history stage. While feeding on adult bees, dispersing V. destructor feed on the abdominal membranes to access to the fat body as reported previously. However, when V. destructor feed on honey bee pupae during their reproductive stage, they primarily consume hemolymph, indicated by wound analysis, preferential transfer of biostains, and a proteomic comparison between parasite and host tissues. Biostaining and proteomic results were paralleled by corresponding findings in Tropilaelaps mercedesae, a mite that only feeds on brood and has a strongly reduced dispersal stage. Metabolomic profiling of V. destructor corroborates differences between the diet of the dispersing adults and reproductive foundresses. The proteome and metabolome differences between reproductive and dispersing V. destructor suggest that the hemolymph diet coincides with amino acid metabolism and protein synthesis in the foundresses while the metabolism of non-reproductive adults is tuned to lipid metabolism. Thus, we demonstrate within-host dietary specialization of ectoparasitic mites that coincides with life history of hosts and parasites.

Predicting Natural Rubber Crystallinity by a Novel Machine Learning Algorithm Based on Molecular Dynamics Simulation Data.

Natural rubber (NR) with excellent mechanical properties, mainly attributed to its strain-induced crystallization (SIC), has garnered significant scientific and technological interest. With the aid of molecular dynamics (MD) simulations, we can investigate the impacts of crucial structural elements on SIC on the molecular scale. Nonetheless, the computational complexity and time-consuming nature of this high-precision method constrain its widespread application. The integration of machine learning with MD represents a promising avenue for enhancing the speed of simulations while maintaining accuracy. Herein, we developed a crystallinity algorithm tailored to the SIC properties of natural rubber materials. With the data enhancement algorithm, the high evaluation value of the prediction model ensures the accuracy of the computational simulation results. In contrast to the direct utilization of small sample prediction algorithms, we propose a novel concept grounded in feature engineering. The proposed machine learning (ML) methodology consists of (1) An eXtreme Gradient Boosting (XGB) model to predict the crystallinity of NR; (2) a generative adversarial network (GAN) data augmentation algorithm to optimize the utilization of the limited training data, which is utilized to construct the XGB prediction model; (3) an elaboration of the effects induced by phospholipid and protein percentage (ω), hydrogen bond strength (εH), and non-hydrogen bond strength (εNH) of natural rubber materials with crystallinity prediction under dynamic conditions are analyzed by employing weight integration with feature importance analysis. Eventually, we succeeded in concluding that εH has the most significant effect on the strain-induced crystallinity, followed by ω and finally εNH.

Topical injection of sclerosant to treat cheek subcutaneous venous malformation resulting in blindness: a case report.

Loss of vision after topical injection of sclerosant is a rare and uncommon complication. We describe a case with vision loss following the facial injections of physician-compounded (PCP) foam sclerotherapy which was created by room air. A 3-year-old boy underwent injection of 5ml polidocanol foamed with room air to treat the venous malformation on the cheek near the left orbit. The boy experienced the whole facial swelling on day 2 after the third injection, especially involving the left side, the visual acuity in the left eye was counting fingers at 30 cm and the swelling reduced at 7 days later after referral. Fundus examination on day 15 revealed hemorrhage inferior to the optic disc and fluorescein angiography revealed blocked fluorescein. The OCT on day 15 showed the edema of the nerve fiber layer beside the fovea. The patient's hearing was also impaired. PCP foam sclerotherapy with room air produced in typical concentrations, preparations as well as volumes always causes vision loss among children. Continued evaluation on the effects of product, gas, volume, and patient age identify optimal approaches will avoid the toxicity and side-effects caused by facial foam sclerotherapy.

DCX-EMAP is a core organizer for the ultrastructure of Drosophila mechanosensory organelles.

Mechanoreceptor cells develop specialized mechanosensory organelles (MOs), where force-sensitive channels and supporting structures are organized in an orderly manner to detect forces. It is intriguing how MOs are formed. Here, we address this issue by studying the MOs of fly ciliated mechanoreceptors. We show that the main structure of the MOs is a compound cytoskeleton formed of short microtubules and electron-dense materials (EDMs). In a knock-out mutant of DCX-EMAP, this cytoskeleton is nearly absent, suggesting that DCX-EMAP is required for the formation of the MOs and in turn fly mechanotransduction. Further analysis reveals that DCX-EMAP expresses in fly ciliated mechanoreceptors and localizes to the MOs. Moreover, it plays dual roles by promoting the assembly/stabilization of the microtubules and the accumulation of the EDMs in the MOs. Therefore, DCX-EMAP serves as a core ultrastructural organizer of the MOs, and this finding provides novel molecular insights as to how fly MOs are formed.

Specificity of affective dynamics of bipolar and major depressive disorder.

OBJECTIVE: Here, we examine whether the dynamics of the four dimensions of the circumplex model of affect assessed by ecological momentary assessment (EMA) differ among those with bipolar disorder (BD) and major depressive disorder (MDD). METHODS: Participants aged 11-85 years (n = 362) reported momentary sad, anxious, active, and energetic dimensional states four times per day for 2 weeks. Individuals with lifetime mood disorder subtypes of bipolar-I, bipolar-II, and MDD derived from a semistructured clinical interview were compared to each other and to controls without a lifetime history of psychiatric disorders. Random effects from individual means, inertias, innovation (residual) variances, and cross-lags across the four affective dimensions simultaneously were derived from multivariate dynamic structural equation models. RESULTS: All mood disorder subtypes were associated with higher levels of sad and anxious mood and lower energy than controls. Those with bipolar-I had lower average activation, and lower energy that was independent of activation, compared to MDD or controls. However, increases in activation were more likely to perpetuate in those with bipolar-I. Bipolar-II was characterized by higher lability of sad and anxious mood compared to bipolar-I and controls but not MDD. Compared to BD and controls, those with MDD exhibited cross-augmentation of sadness and anxiety, and sadness blunted energy. CONCLUSION: Bipolar-I is more strongly characterized by activation and energy than sad and anxious mood. This distinction has potential implications for both specificity of intervention targets and differential pathways underlying these dynamic affective systems. Confirmation of the longer term stability and generalizability of these findings in future studies is necessary.

Clinical relevance and distribution of Helicobacter pylori virulence factors in isolates from Chinese patients.

Background: At present, the relationship between virulence factors of Helicobacter pylori (H. pylori) and gastrointestinal diseases is still under discussion. This study investigated the association between distinct virulence factors in H. pylori and different gastrointestinal diseases. Methods: Gastric biopsy specimens were obtained from 160 patients with different gastrointestinal diseases in China, including 77 patients with chronic gastritis (CG), 36 with peptic ulcer disease (PUD), and 38 with gastric carcinoma (GC). The presence of certain virulence genes was determined by polymerase chain reaction (PCR), and the results were analyzed using chi-squared tests. Results: A total of 160 H. pylori strains were successfully isolated from gastric biopsy specimens. Overall, all strains of H. pylori were cagA, cagE positive, and the most common vacA genotypes were s1 (98.8%) and m2 (68.1%). The positive rates of the jhp0562, jhp0563, homA, homB, hopQI, and hopQII genes were 99.4%, 32.5%, 33.1%, 71.3%, 100%, and 6.9%, respectively. There was no significant association between these genes and different disease types. The dominant hpyIIIR-positive genotype was detected in 83.1% of the strains, making it significantly more prevalent than the hrgA-positive genotype (P<0.001). Surprisingly, the mixed genotype of hrgA and hpyIIIR was common and accounted for 41.3%. The hrgA-positive strains were more common in GC patients (71.1%) compared to CG patients (50.7%, P<0.05). The mixed genotype was prevalent and accounted for 55.3% and 31.2% of strains from GC and CG patients, respectively. Multivariate analysis showed that the hrgA gene exhibited a positive correlation with GC and increased the risk of GC [odds ratio (OR) =3.606, P<0.05]. In contrast, the presence of hrgA exhibited a negative correlation with CG (OR =0.499, P<0.05). Conclusions: These results suggested that the universal presence of cagA, cagE, vacA s1, jhp0562, homB, and hopQI made it impossible to examine disease-specific associations with any of these virulence factors. In addition, they may synergistically contribute to more virulent strains and severe diseases in China. Furthermore, there was a strong association between the hrgA gene and progression to GC, indicating the potential application of other virulence factors in clinical detection.

Small Intestinal Bacterial Overgrowth in Patients with Gallbladder Polyps: A Cross-Sectional Study.

Purpose: There is probably a high prevalence of small intestinal bacterial overgrowth (SIBO) in patients with gallbladder polyps (GBPs). To date, no study has evaluated the occurrence of SIBO in patients with GBPs. The aim of this study was to investigate the prevalence of SIBO in patients with GBPs and explore the possible association between these two conditions. Patients and Methods: The hydrogen-methane breath test was used to diagnose SIBO, and patients were divided into GBPs and control groups based on whether GBPs were found under ultrasound. Clinical and paraclinical factors were compared between the two groups. Results: A total of 297 subjects were included in this study. The prevalence of SIBO was significantly higher in the GBPs group than in the control group (50.0% vs.30.8%, p<0.01). Multivariate logistic regression analysis showed that male (OR=2.26, 95% CI=1.12-4.57, p=0.023), SIBO (OR=3.21, 95% CI=1.69-6.11, p<0.001), fatty liver (OR=2.91, 95% CI= 1.50-5.64, p=0.002) and BMI (OR=1.13, 95% CI=1.01-1.26, p=0.035) were independently associated with GBPs. And by subgroup analysis, we found that the association between SIBO and GBPs was stronger in females than in males (p for interaction< 0.001). In addition, SIBO (OR=5.11, 95% CI=1.42-18.36, p=0.012) and fasting glucose (OR=3.04, 95% CI=1.27-7.28, p=0.013) were found to be associated with solitary polyps. Conclusion: SIBO was highly prevalent in patients with GBPs, and this association seemed to be stronger among females.

Spontaneous cerebrospinal fluid rhinorrhea associated with an incidental pituitary adenoma.

Spontaneous cerebrospinal fluid (CSF) rhinorrhea presenting as the sole symptom of untreated pituitary adenoma is rare, with only 15 cases having been reported in the English literature. All these untreated pituitary adenoma contributing to spontaneous CSF rhinorrhea were diagnosed by the preoperative neuroimaging. Herein, we described an extraordinary rare patient with a pituitary microadenoma, presenting with spontaneous CSF rhinorrhea as the sole symptom. However, this pituitary microadenoma was only found incidentally at surgery, not preoperatively. To the best knowledge of us, this is the first reported case of spontaneous CSF rhinorrhea associated with an untreated pituitary adenoma diagnosed at surgery.

Cardamine violifolia as a potential Hg hyperaccumulator and the cellular responses.

Cardamine violifolia belongs to the Brassicaceae family and is a selenium (Se) hyperaccumulator found in Enshi, China. In this study, C. violifolia was found to accumulate mercury (Hg) in its roots and aboveground parts at concentrations up to 6000 µg/g. In the seedling and mature stages, the bioaccumulation factors (BAFS) of Hg reached 1.8-223, while the translocation factor (TF) for Hg reached 1.5. We observed a significant positive correlation between THg concentrations in plant tissues and those in the soil (r2 = 0.71-0.84). Synchrotron radiation X-ray fluorescence with focused X-ray (µ-SRXRF) showed that Hg was translocated from the roots to shoots through the vascular bundle and was transported through the leaf veins in leaves. Transmission electron microscopy showed that root cells were more tolerant to Hg than leaf cells. These findings provide insights into the mechanisms of Hg hyperaccumulation in C. violifolia. Overall, we demonstrated that C. violifolia is a promising Hg hyperaccumulator that may be used for phytoremediating Hg-contaminated farmlands.

Comorbidity and Coaggregation of Major Depressive Disorder and Bipolar Disorder and Cannabis Use Disorder in a Controlled Family Study.

Importance: Cannabis use disorder (CUD) is increasing in the US. Clarification of the potential mechanisms underlying the comorbidity between mood disorders and CUD may help prevent CUD. Objective: To examine co-occurrence and familial aggregation of CUD and mood disorder subtypes. Design, Setting, and Participants: In this cross-sectional, community-based study in the Washington, DC, metropolitan area, semistructured diagnostic interviews and family history reports assessed lifetime DSM-IV disorders in probands and relatives. Familial aggregation and coaggregation of CUD with mood disorders were estimated via mixed-effects models, adjusting for age, sex, recruitment source, and comorbid mood, anxiety, and other substance use disorders. A total of 586 adult probands (186 with bipolar disorder; 55 with CUD) and 698 first-degree relatives (91 with bipolar disorder; 68 with CUD) were recruited from a community screening of the greater Washington, DC, metropolitan area from May 2004 to August 2020. Inclusion criteria were ability to speak English, and availability and consent to contact at least 2 living first-degree relatives. Main Outcomes and Measures: Lifetime CUD in first-degree relatives. Results: Of 586 probands, 395 (67.4%) were female; among 698 relatives, 437 (62.6%) were female. The mean (SD) age was 47.5 (15.2) years for probands and 49.6 (18.0) years for relatives. In the proband group, 82 participants (14.0%) self-identified as African American or Black, 467 (79.7%) as White, and 37 (6.3%) as American Indian or Alaska Native, Asian, more than one race, or another race or ethnicity or declined to respond. In the relative group, 53 participants (7.6%) self-identified as African American or Black, 594 (85.1%) as White, and 51 (7.3%) as American Indian or Alaska Native, Asian, more than one race, or another race or ethnicity or declined to respond. These groups were combined to protect privacy owing to small numbers. CUD in probands (55 [9.4%]) was associated with an increase in CUD in relatives (adjusted odds ratio [aOR], 2.64; 95% CI, 1.20-5.79; P = .02). Bipolar disorder II (BP-II) in probands (72 [12.3%]) was also associated with increased risk of CUD in relatives (aOR, 2.57; 95% CI, 1.06-6.23; P = .04). However, bipolar disorder I (114 [19.5%]) and major depressive disorder (192 [32.8%]) in probands were not significantly associated with CUD in relatives. Among relatives, CUD was associated with BP-II (aOR, 4.50; 95% CI, 1.72-11.77; P = .002), major depressive disorder (aOR, 3.64; 95% CI, 1.78-7.45; P < .001), and mean (SD) age (42.7 [12.8] years with CUD vs 50.3 [18.3] years without CUD; aOR, 0.98; 95% CI, 0.96-1.00; P = .02). Familial coaggregation of BP-II with CUD was attenuated by the inclusion of comorbid anxiety disorders. Further, rates of CUD were highest in relatives with both a familial and individual history of BP-II (no familial or individual history of BP-II: 41 [7.2%]; familial history but no individual history of BP-II: 13 [19.1%]; individual history but no familial history of BP-II: 10 [22.2%]; familial and individual history of BP-II: 4 [28.6%]; Fisher exact test, P < .001). The onset of mood disorder subtypes preceded CUD in probands and relatives in most cases. Conclusions and Relevance: The findings confirmed a familial aggregation of CUD. The increase in risk of CUD among relatives of probands with BP-II suggests that CUD may share a common underlying diathesis with BP-II. Taken together with the temporal precedence of depression and mania with respect to CUD onset, these findings highlight a potential role for BP-II intervention as CUD prevention.

A Machine Learning Framework to Predict the Tensile Stress of Natural Rubber: Based on Molecular Dynamics Simulation Data.

Natural rubber (NR), with its excellent mechanical properties, has been attracting considerable scientific and technological attention. Through molecular dynamics (MD) simulations, the effects of key structural factors on tensile stress at the molecular level can be examined. However, this high-precision method is computationally inefficient and time-consuming, which limits its application. The combination of machine learning and MD is one of the most promising directions to speed up simulations and ensure the accuracy of results. In this work, a surrogate machine learning method trained with MD data is developed to predict not only the tensile stress of NR but also other mechanical behaviors. We propose a novel idea based on feature processing by combining our previous experience in performing predictions of small samples. The proposed ML method consists of (i) an extreme gradient boosting (XGB) model to predict the tensile stress of NR, and (ii) a data augmentation algorithm based on nearest-neighbor interpolation (NNI) and the synthetic minority oversampling technique (SMOTE) to maximize the use of limited training data. Among the data enhancement algorithms that we design, the NNI algorithm finally achieves the effect of approaching the original data sample distribution by interpolating at the neighborhood of the original sample, and the SMOTE algorithm is used to solve the problem of sample imbalance by interpolating at the clustering boundaries of minority samples. The augmented samples are used to establish the XGB prediction model. Finally, the robustness of the proposed models and their predictive ability are guaranteed by high performance values, which indicate that the obtained regression models have good internal and external predictive capacities.

Comorbidity and familial aggregation of back/neck pain in the NIMH Family Study of Affective Spectrum Disorders.

OBJECTIVE: Back pain is associated with substantial Global Burden of Disease and is highly comorbid with mood and anxiety symptoms and syndromes. However, mechanisms underlying this association have not been well-elucidated. Here we apply data from the NIMH Family Study of Affective Spectrum Disorders to investigate the comorbidity, familial aggregation, and cross-aggregation of back/neck pain with mood disorder subtypes. METHODS: The sample includes 519 probands and 560 interviewed first-degree relatives. Lifetime DSM-IV Bipolar I, Bipolar II, and Major Depressive Disorder [MDD] were derived from semi-structured diagnostic interviews. Lifetime history of back or neck pain and its age of onset were self-reported retrospectively. Familial aggregation and cross-aggregation were estimated via mixed effects models in probands and interviewed first-degree relatives, while heritability and co-heritability (endophenotypic ranking value [ERV]) were estimated using full pedigrees. RESULTS: Over 45% of participants endorsed a history of back/neck pain. Back/neck pain was familial (adjusted odds ratio [aOR] 1.5, p = 0.04; h2 = 0.24, p = 0.009). Back/neck pain in probands was associated with MDD in relatives (aOR 1.5, p = 0.04; ERV = 0.17, p = 0.024), but not with bipolar disorder. Onset of back/neck pain occurred earlier in those with bipolar disorder compared to controls. CONCLUSION: Findings suggest common familial risk factors underlying back/neck pain with MDD, whereas there was within-individual comorbidity of bipolar with back/neck pain. Future studies that identify common factors that lead to either back/neck pain or MDD can inform prevention and interventions.

UBE2W Improves the Experimental Colitis by Inhibiting the NF-κB Signaling Pathway.

BACKGROUND: The NF-κB signaling cascade regulates immune response and is often dysregulated in tumor development. UBE2W is a novel type I ubiquitin-conjugating enzyme (E2) whose biological function is still unclear. AIMS: This study was designed to investigate whether UBE2W regulates NF-κB signaling pathway and is involved in the progression of experimental colitis. METHODS: At the cellular level, the effect of UBE2W on NF-κB transcriptional activity was measured using a dual-luciferase reporter assay. The influence of UBE2W on NF-κB pathway activation and the entry of p65 into the nucleus were determined by Western blot and immunofluorescence analyses, respectively. Moreover, the colitis model was established by administering 2.5% dextran sulfate sodium (DSS)/water to UBE2W overexpression, UBE2W-knockdown and control mice. Body weight, stool consistency, colon length and clinical severity were examined. Expression of pro-inflammatory cytokines and phosphorylation of p65 and IκB in the colon tissue were measured by qRT-PCR and Western blot, respectively. RESULTS: UBE2W inhibited TNFα-induced NF-κB transcription activity, attenuated IκB and p65 phosphorylation, downregulated TNFα and IL-8 expression and blocked the entry of p65 into the nucleus. In the DSS-induced colitis model, UBE2W-knockdown mice had increased weight loss, more serious diarrhea and mucosal injures compared with the control mice. Moreover, phosphorylation of IκB and p65 and the expression of pro-inflammatory mediators such as TNFα, IL-6 were significantly increased in UBE2W knockdown mice. However, these changes were completely reversed in UBE2W overexpression mice. CONCLUSIONS: The overexpression of UBE2W ameliorates the severity of DSS-induced colitis, which may be mediated by inhibiting the expression of pro-inflammatory mediators and activation of the NF-κB signaling pathway. These findings provide evidence that UBE2W might have potential therapeutic implications in IBD.

Association between Small Intestinal Bacterial Overgrowth and Subclinical Atheromatous Plaques.

Background: Several recent studies have reported the relationship between atherosclerosis and gut microbial imbalance. Small intestinal bacterial overgrowth (SIBO) is one of the most common forms of gut microbiota imbalance, and studies have shown that SIBO plays an important role in human health. However, the relationship between SIBO and subclinical atheromatous plaques remains unclear. The aim of this study was to investigate the frequency of subclinical atheromatous plaques in patients with SIBO and to explore the association between these two conditions. Methods: A total of 411 eligible subjects were included in this study. The lactulose hydrogen-methane breath test was used to diagnose SIBO, and ultrasound examinations of the carotid, abdominal aorta and lower extremity arteries were performed in all subjects to assess the presence of plaques. Results: Plaques were more common in the SIBO-positive group than in the SIBO-negative group (abdominal aorta, 74.2% vs. 38.8%, p < 0.01; carotid arteries, 71.7% vs. 52.3, p < 0.01; lower extremity arteries, 73.4% vs. 57.6%, p < 0.01). After adjusting for traditional confounders, compared to the SIBO-negative population, the SIBO-positive population had, respectively, OR = 4.18 (95% CI = 2.56−6.80, p < 0.001), OR = 1.93 (95% CI = 1.23−3.02, p = 0.004), OR = 1.81 (95% CI = 1.14−2.88, p = 0.011) and OR = 5.42 (95% CI = 2.78−10.58, p < 0.001) for abdominal, carotid, lower extremity and any-territory plaque presence. Conclusion: SIBO was found to be associated with subclinical atheromatous plaques, and the mechanism of this association warrants further exploration.

Artificial Intelligence Combined With Big Data to Predict Lymph Node Involvement in Prostate Cancer: A Population-Based Study.

BACKGROUND: A more accurate preoperative prediction of lymph node involvement (LNI) in prostate cancer (PCa) would improve clinical treatment and follow-up strategies of this disease. We developed a predictive model based on machine learning (ML) combined with big data to achieve this. METHODS: Clinicopathological characteristics of 2,884 PCa patients who underwent extended pelvic lymph node dissection (ePLND) were collected from the U.S. National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015. Eight variables were included to establish an ML model. Model performance was evaluated by the receiver operating characteristic (ROC) curves and calibration plots for predictive accuracy. Decision curve analysis (DCA) and cutoff values were obtained to estimate its clinical utility. RESULTS: Three hundred and forty-four (11.9%) patients were identified with LNI. The five most important factors were the Gleason score, T stage of disease, percentage of positive cores, tumor size, and prostate-specific antigen levels with 158, 137, 128, 113, and 88 points, respectively. The XGBoost (XGB) model showed the best predictive performance and had the highest net benefit when compared with the other algorithms, achieving an area under the curve of 0.883. With a 5%~20% cutoff value, the XGB model performed best in reducing omissions and avoiding overtreatment of patients when dealing with LNI. This model also had a lower false-negative rate and a higher percentage of ePLND was avoided. In addition, DCA showed it has the highest net benefit across the whole range of threshold probabilities. CONCLUSIONS: We established an ML model based on big data for predicting LNI in PCa, and it could lead to a reduction of approximately 50% of ePLND cases. In addition, only ≤3% of patients were misdiagnosed with a cutoff value ranging from 5% to 20%. This promising study warrants further validation by using a larger prospective dataset.

Evaluation of Phage Therapy for Pulmonary Infection of Mouse by Liquid Aerosol-Exposure Pseudomonas aeruginosa.

BACKGROUND: Pseudomonas aeruginosa is an important nosocomial infectious bacterium, more and more multidrug resistant P. aeruginosa have been isolated and posed severe challenges to clinical antibiotic treatment, bringing additional morbidity, mortality, and economic burden. Bacteriophages can lyse bacteria specificity and are feasible alternatives to antibiotics. METHODS: A Pseudomonas aeruginosa-infecting phage vB_PaeP_PA01EW was isolated. Phage plaque assays, transmission electron microscopy, host-range determination, infection assay analyses, whole-genome sequencing and annotation were performed for the phage. Mice pneumonia model using liquid aerosol-exposure Pseudomonas aeruginosa was established, and phage therapy was evaluated. RESULTS: vB_PaeP_PA01EW belongs to the family Podoviridae according to transmission electron microscopy and was identified as a Luz24likevirus according to the genome analysis. For the phage therapy, compared with the bacteria-infected group, the phage-rescue group has some characteristics. First, adventitial edema and diffuse infiltration of inflammatory cells in tissues were alleviated, Second, bronchial epithelial cell proliferation was reduced. Third, the bacterial burden was significantly decreased. CONCLUSION: This study provided data support and theoretical basis for the clinical application of bacteriophages. It has important guiding significance and reference value for the application of bacteriophage therapy of other pathogenic bacteria.

Effect of evidence-based nursing intervention on diet and pain after subtotal gastrectomy.

OBJECTIVE: To understand the effect of evidence-based nursing on diet and pain after subtotal gastrectomy. METHODS: From June 2014 to May 2016, 68 patients with gastric cancer undergoing subtotal gastrectomy were selected as the research group (RG) and 57 patients with routine nursing as the control group (CG). The incidence of complications and recovery time were compared between the two groups. The pain and sleep were evaluated by visual analogue scale (VAS) and Pittsburgh Sleep Quality Index (PSQI). The survival condition of the two groups after 3 years of prognosis was observed. RESULTS: The incidence of complications and recovery time in RG were less than those in CG (P < 0.05), and the VAS and PSQI scores in RG were lower than those in CG on the 3rd and 7th day after operation (P < 0.01). However, the nursing satisfaction and 3-year survival rate of RG were higher than those of CG (P < 0.05). CONCLUSION: Evidence-based nursing can effectively reduce postoperative complications and pain in patients with gastric cancer undergoing subtotal gastrectomy.