Airway Reactance Predicts Static Lung Hyperinflation in Severe Asthma.

BACKGROUND AND OBJECTIVES: Background: Static lung hyperinflation (SLH) measured using body plethysmography in patients with asthma is associated with poor outcomes. The severity of SLH may be associated with small airway dysfunction (SAD), which can be measured using impulse oscillometry (IOS). Objective: This study aims to determine the correlation between SLH and SAD in patients with severe asthma and assess the improvement in SLH and SAD with treatment. METHODS: We analyzed data from patients who were enrolled in the Taiwan Severe Asthma Registry, which comprises a prospective observational cohort. Plethysmography and IOS were performed regularly. The relationship between spirometry and IOS parameters was determined. Changes in the clinical outcomes in response to treatment were analyzed. RESULTS: Of 107 patients with severe asthma, 83 (77.6%) had SLH based on an increased residual volume to total lung capacity ratio (RV/ TLC). Most patients were older women with worse pulmonary function and SAD than those without SLH. SAD, defined as increased airway resistance/reactance, was significantly correlated with SLH. Airway reactance at 5 Hz (X5) ≤-0.21 kPa/(L/s) detected SLH with an area under the receiver operating characteristic curve of 0.84 (P<.0001; sensitivity, 85.2%; and specificity, 83.3%). After 12 months, patients who received add-on biologics (vs those who did not) had significantly reduced exacerbations, fractional exhaled nitric oxide level, and blood eosinophil counts, as well as improved forced expiratory volume in the first second, X5, and a trend toward reduced RV/TLC ratio. CONCLUSIONS: In severe asthma, airway reactance (X5) could be a novel parameter for assessing SLH.

Hemorrhagic morbidity in nulliparous patients with placenta previa without placenta accrete spectrum disorders.

Background: Placental adhesion spectrum (PAS) is a disease in which the trophoblast invades the myometrium, and is a well-known high-risk condition associated with placental previa. Aim: The morbidity of nulliparous women with placenta previa without PAS disorders is unknown. Patients and Methods: The data from nulliparous women who underwent cesarean delivery were collected retrospectively. The women were dichotomized into malpresentation (MP) and placenta previa groups. The placenta previa group was categorized into previa (PS) and low-lying (LL) groups. When the placenta covers the internal cervical os, it is called placenta previa, when the placenta is near the cervical os, it is called the low-lying placenta. Their maternal hemorrhagic morbidity and neonatal outcomes were analyzed and adjusted using multivariate analysis based on univariate analysis. Results: A total of 1269 women were enrolled: 781 women in the MP group and 488 women in the PP-LL group. Regarding packed red blood cell transfusion, PP and LL had adjusted odds ratio (aOR) of 14.7 (95% confidence interval (CI): 6.6 - 32.5), and 11.3 (95% CI: 4.9 - 26) during admission, and 51.2 (95% CI: 22.1 - 122.7) and 10.3 (95% CI: 3.9 - 26.6) during operation, respectively. For intensive care unit admission, PS and LL had aOR of 15.9 (95% CI: 6.5 - 39.1) and 3.5 (95% CI: 1.1 - 10.9), respectively. No women had cesarean hysterectomy, major surgical complications, or maternal death. Conclusion: Despite placenta previa without PAS disorders, maternal hemorrhagic morbidity was significantly increased. Thus, our results highlight the need for resources for those women with evidence of placenta previa including a low-lying placenta, even if those women do not meet PAS disorder criteria. In addition, placenta previa without PAS disorder was not associated with critical maternal complications.

Determining the gluonic gravitational form factors of the proton.

The proton is one of the main building blocks of all visible matter in the Universe1. Among its intrinsic properties are its electric charge, mass and spin2. These properties emerge from the complex dynamics of its fundamental constituents-quarks and gluons-described by the theory of quantum chromodynamics3-5. The electric charge and spin of protons, which are shared among the quarks, have been investigated previously using electron scattering2. An example is the highly precise measurement of the electric charge radius of the proton6. By contrast, little is known about the inner mass density of the proton, which is dominated by the energy carried by gluons. Gluons are hard to access using electron scattering because they do not carry an electromagnetic charge. Here we investigated the gravitational density of gluons using a small colour dipole, through the threshold photoproduction of the J/ψ particle. We determined the gluonic gravitational form factors of the proton7,8 from our measurement. We used a variety of models9-11 and determined, in all cases, a mass radius that is notably smaller than the electric charge radius. In some, but not all cases, depending on the model, the determined radius agrees well with first-principle predictions from lattice quantum chromodynamics12. This work paves the way for a deeper understanding of the salient role of gluons in providing gravitational mass to visible matter.

Laparoscopic total extra-peritoneal (TEP) inguinal hernia repair under local anesthesia by topical lidocaine injection.

PURPOSE: Laparoscopic total extra-peritoneal (TEP) inguinal hernia repair is usually performed under general anesthesia (GA) for muscle relaxation. However, TEP hernia repair may be reluctant in high-risk patients of GA. The aim of this study was to compare the outcomes of the TEP under GA and local anesthesia (LA). METHODS: We retrospectively analyzed patients with inguinal hernia who underwent TEP under GA or LA in a single center from December 2016 to May 2018. The outcomes, such as demographics, duration of surgery, length of hospital stay, visual analog scale (VAS), and postoperative complications, were compared in each group. RESULTS: Seventy-six patients with inguinal hernia underwent TEP under GA (n = 52) or LA (n = 24). Total operation time (mean ± standard deviation; GA, 111.6 ± 23.0 min; LA, 76.3 ± 18.0 min; p < 0.001) and length of hospital stay (GA, 38.3 ± 11.6 min; LA, 30.3 ± 15.6 min; p < 0.014) were shorter in LA group compared to GA group. There were no significant differences in postoperative VAS (1 h, p = 0.247; 4 h, p = 0.086; 12 h, p = 0.469; 24 h, p = 0.411), postoperative adverse effects (vomiting, p = 0.570; urinary retention, p = 0.214; headache, p = 0.494), and postoperative complications (seroma, p = 0.348; scrotal edema, p = 0.178; recurrence, p = 0.822) between LA group and GA group. CONCLUSION: Compared with GA, there were no differences in postoperative pain and complications in patients who underwent TEP hernia repair under LA. Furthermore, in LA group, total operation time and length of hospital stay were shortened.

Onychopapilloma: its clinical, dermoscopic and pathologic features.

BACKGROUND: Onychopapilloma is a benign tumour of the nail bed and distal matrix and commonly presents as longitudinal erythronychia, longitudinal leukonychia or longitudinal melanonychia. Because onychopapilloma is rare, its clinical characteristics and dermoscopic findings have not been well investigated in Asia. OBJECTIVES: This study aimed to investigate the clinical characteristics and dermoscopic and pathologic findings of onychopapilloma in Korea. METHODS: We retrospectively reviewed the medical records and clinical/dermoscopic photographs of 39 patients diagnosed with onychopapilloma in the Pusan National University Hospitals (Busan and Yangsan) for 11 years (2010-2021). RESULTS: Among 39 patients, 23 (59.0%) were men, and 16 (41.0%) were women. The mean age was 46.1 (16-77) years. All lesions were single, and most of them were located on the fingers (92.3%), especially the thumb (66.7%). The most common clinical feature was longitudinal erythronychia (56.4%), and the most common dermoscopic finding was distal subungual hyperkeratosis (100%). We found two new dermoscopic features: macrolunula and trailing lunula along the longitudinal band. Among 18 patients who underwent surgical excision, only 6 (33.3%) showed typical acanthosis and papillomatosis on the nail bed. CONCLUSIONS: We found that Asian onychopapilloma has similar clinicodermoscopic findings to the Caucasian one, that is to say, longitudinal erythronychia and distal subungual hyperkeratosis were the most common nail change and dermoscopic finding, respectively. We propose two new dermoscopic features of onychopapilloma: macrolunula and trailing lunula along the longitudinal band.

Deeply Virtual Compton Scattering Cross Section at High Bjorken x_{B}.

We report high-precision measurements of the deeply virtual Compton scattering (DVCS) cross section at high values of the Bjorken variable x_{B}. DVCS is sensitive to the generalized parton distributions of the nucleon, which provide a three-dimensional description of its internal constituents. Using the exact analytic expression of the DVCS cross section for all possible polarization states of the initial and final electron and nucleon, and final state photon, we present the first experimental extraction of all four helicity-conserving Compton form factors (CFFs) of the nucleon as a function of x_{B}, while systematically including helicity flip amplitudes. In particular, the high accuracy of the present data demonstrates sensitivity to some very poorly known CFFs.

Understanding host-microbiota interactions in the commercial piglet around weaning.

Weaning is a critical period in the life of pigs with repercussions on their health and welfare and on the economy of the swine industry. This study aimed to assess the effect of the commercial early weaning on gut microbiota, intestinal gene expression and serum metabolomic response via an integrated-omic approach combining 16S rRNA gene sequencing, the OpenArray gene expression technology and 1H-NMR spectroscopy. Fourteen piglets from different litters were sampled for blood, jejunum tissue and caecal content two days before (- 2d), and three days after (+ 3d) weaning. A clearly differential ordination of caecal microbiota was observed. Higher abundances of Roseburia, Ruminococcus, Coprococcus, Dorea and Lachnospira genera in weaned piglets compared to prior to weaning showed the quick microbial changes of the piglets' gut microbiota. Downregulation of OCLN, CLDN4, MUC2, MUC13, SLC15A1 and SLC13A1 genes, also evidenced the negative impact of weaning on gut barrier and digestive functions. Metabolomic approach pinpointed significant decreases in choline, LDL, triglycerides, fatty acids, alanine and isoleucine and increases in 3-hydroxybutyrate after weaning. Moreover, the correlation between microbiota and metabolome datasets revealed the existence of metabolic clusters interrelated to different bacterial clusters. Our results demonstrate the impact of weaning stress on the piglet and give insights regarding the associations between gut microbiota and the animal gene activity and metabolic response.

Deep Exclusive Electroproduction of π

We report measurements of the exclusive neutral pion electroproduction cross section off protons at large values of x_{B} (0.36, 0.48, and 0.60) and Q^{2} (3.1 to 8.4 GeV^{2}) obtained from Jefferson Lab Hall A experiment E12-06-014. The corresponding structure functions dσ_{T}/dt+εdσ_{L}/dt, dσ_{TT}/dt, dσ_{LT}/dt, and dσ_{LT^{'}}/dt are extracted as a function of the proton momentum transfer t-t_{min}. The results suggest the amplitude for transversely polarized virtual photons continues to dominate the cross section throughout this kinematic range. The data are well described by calculations based on transversity generalized parton distributions coupled to a helicity flip distribution amplitude of the pion, thus providing a unique way to probe the structure of the nucleon.

Short communication: Preweaning socialization and environmental enrichment affect short-term performance after regrouping in commercially reared pigs.

On-farm practices like premature weaning and frequent regrouping induce stress to pigs. Early socialization or environmental enrichment in piglets reduce weaning stress, as suggested in previous studies. Little research with both effects and in commercial settings was found. The aim was to investigate the effects of preweaning socialization and environmental enrichment on life-long performance in 661 Danbred pigs. Two treatments were distinguished during the suckling period: control (CON, 24 litters) and enriched (ENR, 24 litters). Control piglets were raised in barren farrowing pens; ENR piglets were provided with six enrichment objects from birth, and two neighboring litters were socialized from Day (D) 14. Pigs were regrouped on D25 (weaning) and D71 (fattening), while keeping the same treatment. Individual body weight was recorded on D1, 14, 23, 27, 31, 38, 69, 79, and after slaughter (carcass weight, CW). Pigs were slaughtered in six batches. Estimated slaughter weight (ESW) was calculated by CW × 1.25. Body weight, CW, and average daily gain (ADG) were analyzed by linear mixed models. Slaughter age was analyzed by Wilcox Rank-Sum test. Body weight and ESW were adjusted to non-linear models to obtain the predicted growth curves of CON and ENR, from birth to the targeted market weight (TMW, 105 kg). Average daily gain during the suckling, nursery, and fattening periods, and from birth to slaughter, did not differ between treatments. However, ADG of ENR when moving pigs from farrowing to nursery (4-day period) and from nursery to fattening (10-day period), revealed a better performance than CON (+20.6 g/day, P = 0.02; +53 g/day, P = 0.03, respectively). Enriched pigs tended to be slaughtered 2.8 days earlier than CON (P = 0.08). On the other hand, the predicted growth curves showed a non-significant 2-day window of reaching TMW between treatments (P = 0.23). Results suggested that enriching the neonatal environment improved the short-term performance after regrouping, and may benefit the life-long performance by reducing time to reach TMW.

Early socialization and environmental enrichment of lactating piglets affects the caecal microbiota and metabolomic response after weaning.

The aim of this study was to determine the possible impact of early socialization and an enriched neonatal environment to improve adaptation of piglets to weaning. We hypothesized that changes in the microbiota colonization process and in their metabolic response and intestinal functionality could help the animals face weaning stress. A total of 48 sows and their litters were allotted into a control (CTR) or an enriched treatment (ENR), in which piglets from two adjacent pens were combined and enriched with toys. The pattern of caecal microbial colonization, the jejunal gene expression, the serum metabolome and the intestinal physiology of the piglets were assessed before (-2 d) and after weaning (+ 3d). A differential ordination of caecal microbiota was observed after weaning. Serum metabolome suggested a reduced energetic metabolism in ENR animals, as evidenced by shifts in triglycerides and fatty acids, VLDL/LDL and creatine regions. The TLR2 gene showed to be downregulated in the jejunum of ENR pigs after weaning. The integration of gene expression, metabolome and microbiota datasets confirmed that differences between barren and enriched neonatal environments were evident only after weaning. Our results suggest that improvements in adaptation to weaning could be mediated by a better response to the post-weaning stress.

Vesicular glutamate transporter-immunopositive axons that coexpress neuropeptides in the rat and human dental pulp.

AIM: To examine the type of vesicular glutamate transporter (VGLUT)-immunopositive (+) axons that coexpress neuropeptides in the rat and human dental pulp, which may help understand peripheral mechanism of pulpal inflammatory pain in rats and humans. METHODOLOGY: The trigeminal ganglia (TG) and the dental pulp of the maxillary molar teeth from three male Sprague-Dawley rats weighing 300-330 g and dental pulps of three healthy human (male) maxillary premolar teeth from three 16 to 28-year-old patients extracted for orthodontic treatment were used. The type of VGLUT + axons that coexpress substance P (SP)- and/or calcitonin gene-related peptide (CGRP) and parvalbumin in the rat TG and in the axons of the rat and the human dental pulp was examined by double fluorescence immunohistochemistry and quantitative analysis. Results were analyzed using one-way anova and the Kruskal-Wallis test. RESULTS: SP and CGRP were expressed in many human VGLUT1 + pulpal axons but not in the rat VGLUT1 + TG neurons and pulpal axons (P < 0.05). SP and CGRP were expressed in a considerable number of human VGLUT2 + pulpal axons and also in many rat TG neurons and pulpal axons. The fraction of VGLUT1 + axons expressing parvalbumin was about three times higher in the rat than in the human dental pulp (P < 0.05). CONCLUSIONS: These findings suggest that the types of VGLUT + axons, which release neuropeptides, may be different between the rat and the human dental pulp, raising a possibility that peripheral mechanism of pulpal inflammatory pain may be different between rats and humans.

Uniform spatial pooling explains topographic organization and deviation from receptive-field scale invariance in primate V1.

Receptive field (RF) size and preferred spatial frequency (SF) vary greatly across the primary visual cortex (V1), increasing in a scale invariant fashion with eccentricity. Recent studies reveal that preferred SF also forms a fine-scale periodic map. A fundamental open question is how local variability in preferred SF is tied to the overall spatial RF. Here, we use two-photon imaging to simultaneously measure maps of RF size, phase selectivity, SF bandwidth, and orientation bandwidth-all of which were found to be topographically organized and correlate with preferred SF. Each of these newly characterized inter-map relationships strongly deviate from scale invariance, yet reveal a common motif-they are all accounted for by a model with uniform spatial pooling from scale invariant inputs. Our results and model provide novel and quantitative understanding of the output from V1 to downstream circuits.

Comparison of dermoscopic features between congenital and acquired acral melanocytic nevi in Korean patients.

BACKGROUND: The dermoscopic patterns of acral melanocytic nevi (AMNs) are crucial in differentiating them from acral melanoma. Several studies have reported the dermoscopic patterns of acquired acral melanocytic nevi (AAMNs). However, few have investigated the dermoscopic patterns of congenital acral melanocytic nevi (CAMNs). OBJECTIVE: To compare the clinical and dermoscopic features of CAMNs and AAMNs. METHODS: The present study included 43 patients with CAMNs and 40 with AAMNs. We reviewed their medical records as well as their clinical and dermoscopic findings. RESULTS: Congenital acral melanocytic nevis were more asymmetrical than AAMNs (P = 0.002) and presented more frequently as comma-shaped (P = 0.005). Regarding dermoscopic findings, globular pattern (55.8%) was the most common feature of CAMNs, while parallel furrow pattern (37.5%) was the most common feature of AAMNs. The presence of fibrillar, globular, and parallel ridge patterns, and diffuse multi-component pigmentation differed significantly between the groups (P < 0.05). Furthermore, CAMNs showed melanoma-specific dermoscopic patterns, such as parallel ridge (18.6%) and diffuse multi-component pigmentation (25.6%). CONCLUSION: The dermoscopic patterns of CAMNs and AAMNs differed markedly. In terms of dermoscopic patterns, CAMNs resembled acral melanoma more often than AAMNs did.

Twelve-day medium pumping into tubular cell-laden scaffold using a lab-made PDMS connector.

In the current study, a method is proposed to supply culture medium into a two-layered cell-laden tubular scaffold in order to enhance cell proliferation, confluence, and viability. The two-layered cell-laden tubular scaffold was made of calcium-alginate mixed with fibroblast cells (NIH/3T3) using a lab-made double- coaxial laminar-flow generator. Afterwards, the tubular scaffold was connected to a syringe pump system using a polydimethylsiloxane (PDMS) micro-connector for long-term cell culture. Three medium pumping conditions were applied and compared: a heart-beat-mimicking pumping (20 µL/s, 1 s period, and 50 % pulse width), a continuous pumping (20 µL/s) and a non-pumping. Non-leaky connections between the tubular scaffolds and the micro-connector outlet were sustained for 13.5 ± 0.83 d in heartbeat-mimicking pumping and 11.8 ± 0.33 d in continuous pumping condition, due to the elasticity of the tubular scaffolds. Importantly, the two pumping conditions resulted in more cell proliferation, confluence, and viability than the non-pumping condition. Furthermore, analysis of newly-produced type-I collagen matrix indicated that the cells under the two pumping conditions formed a tissue-like structure. The proposed technique could further be applied to vascular co-culturing for vascular engineered tissue.

Interventional treatment of bleeding complications due to percutaneous cannulation for peripheral extracorporeal membrane oxygenation.

PURPOSE: This study aimed to evaluate the safety and effectiveness of interventional techniques as a treatment for bleeding complications secondary to percutaneous cannulation for peripheral extracorporeal membrane oxygenation (PECMO). MATERIALS AND METHODS: Out of 1264 patients who underwent PECMO at our hospital between January 2009 and September 2018, we reviewed the clinical characteristics and outcomes of eight patients (4 men, 4 women; mean age, 54.9 years [range, 31-77 years]) who underwent percutaneous interventional treatment for bleeding complications secondary to percutaneous cannulation for PECMO. RESULTS: Both hemodynamic instability and coagulopathy were present in 7 patients who had direct injury during PECMO insertion and absent in one patient with pseudoaneurysm at the PECMO removal site. Percutaneous ultrasound-guided thrombin injection was performed in three patients with pseudoaneurysm of the common or superficial femoral artery, and adjunctive embolization was combined with microcoils or n-butyl 2-cyanoacrylate in two of them. Stent graft was inserted in four patients with contrast extravasation (n=3) from external iliac artery (n=1) or common femoral or iliac veins (n=2) ruptures or the fistula between the superficial femoral artery and vein (n=1). N-butyl 2-cyanoacrylate and coil embolization was performed for pseudoaneurysm from the internal pudendal artery branch in the remaining one patient. Technical success was achieved in all eight patients. There were no procedure-related complications. There was no rebleeding during the follow-up. CONCLUSION: Interventional treatment is a safe, technically feasible and therapeutically effective modality for treating bleeding complications secondary to a percutaneous cannulation for PECMO.

Bioinks and bioprinting technologies to make heterogeneous and biomimetic tissue constructs.

The native tissues are complex structures consisting of different cell types, extracellular matrix materials, and biomolecules. Traditional tissue engineering strategies have not been able to fully reproduce biomimetic and heterogeneous tissue constructs because of the lack of appropriate biomaterials and technologies. However, recently developed three-dimensional bioprinting techniques can be leveraged to produce biomimetic and complex tissue structures. To achieve this, multicomponent bioinks composed of multiple biomaterials (natural, synthetic, or hybrid natural-synthetic biomaterials), different types of cells, and soluble factors have been developed. In addition, advanced bioprinting technologies have enabled us to print multimaterial bioinks with spatial and microscale resolution in a rapid and continuous manner, aiming to reproduce the complex architecture of the native tissues. This review highlights important advances in heterogeneous bioinks and bioprinting technologies to fabricate biomimetic tissue constructs. Opportunities and challenges to further accelerate this research area are also described.

Oncogenes expand during evolution to withstand somatic amplification.

Background: Cancer-related genes are under intense evolutionary pressure. We conjectured that gene size is an important determinant of amplification propensity for oncogenes and thus cancer susceptibility and therefore could be subject to natural selection. Patients and methods: Gene information, including size and genomic locations, of all protein-coding genes were downloaded from Ensembl (release 87). Quantification of gene amplification was based on Genomic Identification of Significant Targets in Cancer scores obtained from available The Cancer Genome Atlas studies. Results: Oncogenes are larger in size as compared with non-cancer genes (mean size: 92.1 kb versus 61.4 kb; P < 0.0001) in the human genome, which is contributed by both increased total exon size (mean size: 4.6 kb versus 3.4 kb; P < 0.0001) and higher intronic content (mean %: 84.8 versus 78.0; P < 0.01). Such non-random size distribution and intronic composition are conserved in mouse and Drosophila (all P < 0.0001). Stratification by gene age indicated that young oncogenes have been subject to a stronger evolutionary pressure for gene expansion than their non-cancer counterparts. Pan-cancer analysis demonstrated that larger oncogenes were amplified to a lesser extent. Tumor-suppressor genes also moved toward small oncogenes in the course of evolution. Conclusions: Oncogenes expand in size whereas tumor-suppressor genes move closer to small oncogenes in the course of evolution to withstand oncogenic somatic amplification. Our findings have shed new light on the previously unappreciated influence of gene size on oncogene amplification and elucidated how cancers have shaped our genome to its present configuration.