Refining silicon nitride waveguide quality through femtosecond laser annealing.

We present a method for modification of silicon nitride (Si3N4) waveguide resonators using femtosecond laser annealing. The quality (Q) factor of the waveguide resonators can be improved by approximately 1.3 times after annealing. Notably, waveguides that originally had a high Q value maintained their quality after the annealing process. However, those with a lower initial Q value experienced a noticeable improvement post-annealing. To characterize the annealing effect, the surface morphologies of Si3N4 films, both pre- and post-annealing, were analyzed using atomic force microscopy. The findings suggest a potential enhancement in surface refinement. Furthermore, Raman spectroscopy confirmed that the Si3N4 film's composition remains largely consistent with its original state within the annealing power range of 0.6-1.6 W. This research underscores the potential of femtosecond laser annealing as an efficient, cost-effective, and localized technique for fabricating low-loss integrated photonics.

An economical single-shot pulse picker without nonlinear effect and dispersion.

An economical and stable single-shot pulse picker design without dispersion, nonlinear effect, and limitation on wavelength is proposed. This design is composed of a periodic pulse blocker (PPB), a control unit, and a mechanical shutter. It has successfully been applied to the commercial high-fluence femtosecond laser with 11-mm beam diameter, 2-mJ pulse energy, and 1-kHz repetition rate. Significantly, by incorporating commercial optical choppers equipped with custom-designed chopper blades in the PPB, this design can accommodate lasers with fluences reaching 610 mJ/cm2 and the standard 1 kHz repetition rate typical of high-fluence lasers. Furthermore, the proposed design provides a cost-effective substitute compared to using electro-optic modulators or acousto-optic modulators.

IL-21, not IL-17A, exacerbates murine primary biliary cholangitis.

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease caused by intrahepatic bile duct injuries, resulting in fibrosis, cirrhosis, and eventually liver failure. T helper (Th) 17 cells are proposed to involve in the pathogenesis of PBC. However, how and which Th17 cell-derived cytokines affect PBC remains unclear. In this study, we investigated the effects of Th17 effector cytokines, including interleukin (IL)-17A, IL-17F, and IL-21 in PBC using a xenobiotic-induced mouse model of autoimmune cholangitis (inducible chemical xenobiotic models of PBC) treated with cytokine-expressing adeno-associated virus. Our results showed that administration of IL-17A, the well-known main cytokine produced by Th17 cells, did not augment liver inflammation or fibrosis. In contrast, we noted IL-17A-treated mice had lower hepatic Th1 cell numbers and higher hepatic CD11b+Ly6G+ polymorphonuclear myeloid-derived suppressor cell numbers. IL-17F did not alter liver inflammation or fibrosis. However, the administration of IL-21 exacerbated liver inflammatory responses and portal cell infiltration. IL-21 markedly increased the numbers of activated CD8+ T cells and liver tissue-resident memory CD8+ T cells. Moreover, IL-21 aggravates liver fibrosis in mice with autoimmune cholangitis. These results emphasized that not IL-17A but IL-21 in Th17 cell-derived cytokines affected the pathogenesis of PBC. IL-21 enhanced liver inflammation and progression to fibrosis by enhancing the numbers and effector activities of CD8+ T cells. Delineation of the effects of different Th17 effector cytokines in PBC offers clues for developing new therapeutic approaches.

Deep learning-based photodamage reduction on harmonic generation microscope at low-level optical power.

The trade-off between high-quality images and cellular health in optical bioimaging is a crucial problem. We demonstrated a deep-learning-based power-enhancement (PE) model in a harmonic generation microscope (HGM), including second harmonic generation (SHG) and third harmonic generation (THG). Our model can predict high-power HGM images from low-power images, greatly reducing the risk of phototoxicity and photodamage. Furthermore, the PE model trained only on normal skin data can also be used to predict abnormal skin data, enabling the dermatopathologist to successfully identify and label cancer cells. The PE model shows potential for in-vivo and ex-vivo HGM imaging.

Regulatory T cells in inflamed liver are dysfunctional in murine primary biliary cholangitis.

Primary biliary cholangitis (PBC) is a chronic autoimmune disease characterized by immune-mediated destruction of intrahepatic small bile ducts. CD8 T cells play a critical role in biliary destruction. However, regulatory T cells (Tregs) have also been identified in the portal tracts of PBC patients. This study tested the hypothesis that hepatic Tregs in PBC were dysfunctional in suppressing immune responses in disease by using our human PBC-like autoimmune cholangitis (AIC) mouse model induced by 2-octynoic acid-conjugated ovalbumin (2-OA-OVA). Our results showed that female and male mice immunized with 2-OA-OVA developed AIC; however, female AIC mice had more severe liver inflammation and fibrosis than male AIC mice. Levels of functional effector CD8 T cells and their chemoattractants, CXCL9 and CXCL10, in the liver were markedly elevated in female AIC mice than in male AIC mice. These results reinforce that CD8 T cells are the primary effector cells in PBC. The number of hepatic Tregs in AIC mice was also higher than in saline-treated mice, but there was no difference between male and female AIC mice. The suppressive function of AIC Tregs was evident despite a discrepancy in the changes in their co-inhibitory receptors and inhibitory cytokines. However, the expansion of hepatic Tregs by low-dose IL-2 treatment did not reduce immune responses to AIC, which may be due to the dysfunction of Tregs in inhibiting T cells. In conclusion, the function of Tregs in the inflamed liver of PBC was insufficient, and low-dose IL-2 treatment could not restore their function to suppress pathological immune responses. Transferring normal Tregs or directly targeting effector CD8 T cells may be beneficial for treating PBC.

RepE: unsupervised representation learning for image enhancement in nonlinear optical microscopy.

We present an unsupervised learning denoising method, RepE (representation and enhancement), designed for nonlinear optical microscopy images, such as second harmonic generation (SHG) and two-photon fluorescence (TPEF). Addressing the challenge of effectively denoising images with various noise types, RepE employs an encoder network to learn noise-free representations and a reconstruction network to generate denoised images. It offers several key advantages, including its ability to (i) operate without restrictive statistic assumptions, (ii) eliminate the need for clean-noisy pairs, and (iii) requires only a few training images. Comparative evaluations on real-world SHG and TPEF images from esophageal cancer tissue slides (ESCC) demonstrate that our method outperforms existing techniques in image quality metrics. The proposed method provides a practical, robust solution for denoising nonlinear optical microscopy images, and it has the potential to be extended to other nonlinear optical microscopy modalities.

Orf Infection on the Scalp of a Taiwanese Woman: A Case Report and Literature Review.

BACKGROUND: Orf, or ecthyma contagiosum, is a zoonosis caused by Parapoxvirus that infects sheep and goats. Human transmission typically occurs in persons in contact with the infected animals or contaminated fomites and environment. In humans, it generally occurs as solitary or multiple skin lesions on the hands or fingers. Involvement of the head region has rarely been reported. CASE PRESENTATION: We report an unusual case with multiple orf lesions on the scalp of a middle-aged woman, along with a review of previously reported Orf cases on the head region. CONCLUSIONS: Although Orf infection rarely happens on the head region, it should be considered in the differential diagnosis of cases with relevant animal exposure.

Apoptotic biliary epithelial cells and gut dysbiosis in the induction of murine primary biliary cholangitis.

Primary biliary cholangitis (PBC) is a female-predominant liver autoimmune disease characterized by the specific immune-mediated destruction of the intrahepatic small bile duct. Although apoptosis of biliary epithelial cells (BECs) and alterations in gut microbiota are observed in patients with PBC, it is still unclear whether these events happen in the early stage and cause the breakdown of tolerance in PBC. In this study, we examined the early events in the loss of tolerance in our well-defined 2-OA-OVA-induced murine autoimmune cholangitis (AIC) model. We report herein that apoptosis of BECs was notable in the early stage of murine AIC. An altered gut microbiota, in particular, an increased percentage of gram-positive Firmicutes in AIC mice was also observed. BECs in AIC mice expressed adhesion molecule ICAM-1, cytokines/chemokines TNF-α, CCL2, CXCL9, CXCL10, and toll-like receptor (TLR) 2. Moreover, BECs treated with TLR2 ligand had elevated apoptosis and CXCL10 production. These data collectively suggest a new mechanism of tolerance breakdown in AIC. Altered gut microbiota induces apoptosis of BECs through TLR2 signaling. BECs secrete chemokines to recruit CD8 T cells to damage BECs further.

Analysis of Functional Arch Support Insoles on the Biomechanics and Performance in Right-Forward Lunging Step of Badminton Players.

The purpose of this study was to examine the differences in biomechanical parameters and sports-specific performance of lower limbs between arch support insoles (ASI) and flat insoles (FLI) when performing net strides. After installing the MVN IMU system, 18 college badminton team members were asked to take the following tests: (1) Consecutive net stride tests; (2) Six-point footwork tests; (3) Retrieve/stroke the ball at the left and right net; (4) Smash and retrieve/stroke the ball at the net; (5) Smash at the front and back crossover step. The joint angle of the lower limbs and ground reaction force during the support phase was collected. The results demonstrated that the peak right hip flexion angle was significantly greater with ASI than FLI (63.09 ± 10.70; 60.08 ± 13.82; p = 0.028), while the peak right foot inversion angle was significantly smaller with ASI than FLI (20.68 ± 7.87; 23.85 ± 8.11; p = 0.013). The principal conclusion was that the arch support insole avoids the decrease in the hip flexion angle and the increase in the foot inversion angle during the net stride tests.

Functional antagonism between ΔNp63α and GCM1 regulates human trophoblast stemness and differentiation.

The combination of EGF, CHIR99021, A83-01, SB431542, VPA, and Y27632 (EGF/CASVY) facilitates the derivation of trophoblast stem (TS) cells from human blastocysts and first-trimester, but not term, cytotrophoblasts. The mechanism underlying this chemical induction of TS cells remains elusive. Here we demonstrate that the induction efficiency of cytotrophoblast is determined by functional antagonism of the placental transcription factor GCM1 and the stemness regulator ΔNp63α. ΔNp63α reduces GCM1 transcriptional activity, whereas GCM1 inhibits ΔNp63α oligomerization and autoregulation. EGF/CASVY cocktail activates ΔNp63α, thereby partially inhibiting GCM1 activity and reverting term cytotrophoblasts into stem cells. By applying hypoxia condition, we can further reduce GCM1 activity and successfully induce term cytotrophoblasts into TS cells. Consequently, we identify mitochondrial creatine kinase 1 (CKMT1) as a key GCM1 target crucial for syncytiotrophoblast differentiation and reveal decreased CKMT1 expression in preeclampsia. Our study delineates the molecular underpinnings of trophoblast stemness and differentiation and an efficient method to establish TS cells from term placentas.

Interleukin-30 Suppresses Not Only CD4+ T Cells but Also Regulatory T Cells in Murine Primary Biliary Cholangitis.

Primary biliary cholangitis (PBC) is a chronic liver autoimmune disease with augmented T helper (Th) 1 and corresponding cytokine IFN-γ immune responses. Using 2-octynoic acid (2-OA) coupled to OVA (2-OA-OVA)-induced mouse models of autoimmune cholangitis (inducible chemical xenobiotic models of PBC), our previous study demonstrated that overexpression of IFN-γ in the model mice enhanced liver inflammation upon disease initiation, but subsequently led to the suppression of chronic inflammation with an increase in interleukin-30 (IL-30) levels. In this study, we investigated whether IL-30 had an immunosuppressive function and whether it could be part of an immune therapeutic regimen for PBC, by treating model mice with murine IL-30-expressing recombinant adeno-associated virus (AAV-mIL-30). We first defined the effects of AAV-mIL-30 in vivo by administering it to a well-known concanavalin A (ConA)-induced hepatitis model of mice and found that AAV-mIL-30 reduced the numbers of activated CD25+CD4+ T cells and the levels of serum IFN-γ and IL-12. In autoimmune cholangitis, decreased numbers of activated CD4+ T cells and Foxp3+ regulatory T cells were noted in the mice treated with AAV-mIL-30 at 3 weeks after the 2-OA-OVA immunization. Treatment with IL-30 did not change the features of autoimmune cholangitis including autoantibodies, cell infiltration, and collagen deposition in the liver at 11 weeks of examination. However, increased levels of cytokines and chemokines were observed. These results suggest that IL-30 suppresses not only CD4+ T cells but also regulatory T cells. Additionally, the administration of IL-30 did not suppress liver inflammation in the murine model of PBC.

Effects of Blue Light on Dynamic Vision.

Dynamic vision is crucial to not only animals' hunting behaviors but also human activities, and yet little is known about how to enhance it, except for extensive trainings like athletics do. Exposure to blue light has been shown to enhance human alertness (Chellappa et al., 2011), perhaps through intrinsically photosensitive retinal ganglion cells (ipRGCs), which are sensitive to motion perception as revealed by animal studies. However, it remains unknown whether blue light can enhance human dynamic vision, a motion-related ability. We conducted five experiments under blue or orange light to test three important components of dynamic vision: eye pursuit accuracy (EPA, Experiment 1), kinetic visual acuity (KVA, Experiment 1 and 2), and dynamic visual acuity (DVA, Experiment 3-5). EPA was measured by the distance between the position of the fixation and the position of the target when participants tracked a target dot. In the KVA task, participants reported three central target numbers (randomly chosen from 0 to 9) moving toward participants in the depth plane, with speed threshold calculated by a staircase procedure. In the DVA task, three numbers were presented along the meridian line on the same depth plane, with motion direction (Experiment 3) and difficulty level (Experiment 4) manipulated, and a blue light filter lens was used to test the ipRGCs contribution (Experiment 5). Results showed that blue light enhanced EPA and DVA, but reduced KVA. Further, DVA enhancement was modulated by difficulty level: blue light enhancement effect was found only with hard task in the downward motion in Experiment 3 and with the low contrast target in Experiment 4. However, this blue light enhancement effect was not caused by mechanism of the ipRGCs, at least not in the range we tested. In this first study demonstrating the relationship between different components of dynamic vision and blue light, our findings that DVA can be enhanced under blue light with hard but not easy task indicate that blue light can enhance dynamic visual discrimination when needed.

Identifying Features that Enhance Older Adults' Acceptance of Robots: A Mixed Methods Study.

BACKGROUND: With global aging, robots are considered a promising solution for handling the shortage of aged care and companionships. However, these technologies would serve little purpose if their intended users do not accept them. While the socioemotional selectivity theory predicts that older adults would accept robots that offer emotionally meaningful relationships, selective optimization with compensation model predicts that older adults would accept robots that compensate for their functional losses. OBJECTIVE: The present study aims to understand older adults' expectations for robots and to compare older adults' acceptance ratings for 2 existing robots: one of them is a more human-like and more service-oriented robot and the other one is a more animal-like and more companion-oriented robot. METHODS: A mixed methods study was conducted with 33 healthy, community-dwelling Taiwanese older adults (age range: 59-82 years). Participants first completed a semi-structured interview regarding their ideal robot. After receiving information about the 2 existing robots, they then completed the Unified Theory of Acceptance and Use of Technology questionnaires to report their pre-implementation acceptance of the 2 robots. RESULTS: Interviews were transcribed for conventional content analysis with satisfactory inter-rater reliability. From the interview data, a collection of older adults' ideal robot characteristics emerged with highlights of humanlike qualities. From the questionnaire data, respondents showed a higher level of acceptance toward the more service-oriented robot than the more companion-oriented robot in terms of attitude, perceived adaptiveness, and perceived usefulness. From the mixed methods analyses, the finding that older adults had a higher level of positive attitude towards the more service-oriented robot than the more companion-oriented robot was predicted by higher expectation or preference for robots with more service-related functions. CONCLUSION: This study identified older adults' preference toward more functional and humanlike robots. Our findings provide practical suggestions for future robot designs that target the older population.

Factors associated with the true location of ingested fishbones.

OBJECTIVES: Fishbone ingestion is a common problem worldwide, and the first step for managing this condition is to locate the fishbone precisely. However, until now, no study has analysed the true location of fishbone and its associated factors. Thus, this study identified the factors predicting the true location of fishbone and subsequently attempted to provide a management algorithm for fishbone ingestion. PATIENTS AND METHODS: This retrospective study was carried out at St Martin De Porres Hospital, Taiwan, between January 2015 and January 2016. All patients were diagnosed as having fishbone ingestion within the pharynx and underwent fishbone removal. RESULTS: This study included 198 consecutive patients with a mean age of 43.1 years (range: 1-84 years). The sensitivity of lateral neck radiography in the diagnosis of fishbone in the pharynx was only 22%. The fishbone locations were as follows: the tonsil in 72 (36.4%) patients, the tongue base / vallecula in 112 (56.6%) and the hypopharynx in 14 (7.0%). Multiple logistic regression analysis showed that patient age and fishbone length were significant independent risk factors associated with the true location of fishbone ingestion. Among all patients, fishbone was removed transorally under direct vision in 73 (36.9%) patients and using flexible nasopharyngoscopy in 125 (63.1%) patients. CONCLUSION: Patient age and fishbone length are important independent factors associated with the location of ingested fishbone. Lateral neck radiography is not beneficial for diagnosing fishbone ingestion within the pharynx. Flexible nasopharyngoscopy, by contrast, is an important method for the diagnosis and treatment of fishbone ingestion within this location.

SFRP3 negatively regulates placental extravillous trophoblast cell migration mediated by the GCM1-WNT10B-FZD7 axis.

Migration of placental extravillous trophoblast (EVT) cells into uterine decidua facilitates the establishment of blood circulation between mother and fetus and is modulated by EVT-decidual cell interaction. Poor or excessive EVT migration is associated with pregnancy complications such as preeclampsia or placenta accreta. Glial cells missing 1 (GCM1) transcription factor is essential for placental development, and decreased GCM1 activity is detected in preeclampsia. To study whether GCM1 regulates trophoblast cell migration, here we showed that GCM1 promotes BeWo and JAR trophoblast cell migration through a novel target gene, WNT10B. Moreover, WNT10B signaling stimulated cytoskeletal remodeling via Rac1 and frizzled 7 (FZD7) was identified as the cognate receptor for WNT10B to up-regulate cell migration. We further showed that secreted frizzled-related protein 3 (SFRP3) is expressed in uterine decidual cells by immunohistochemistry and that SFRP3 expression in telomerase-transformed human endometrial stromal cells (T-HESCs) is elevated under decidualization stimuli and further enhanced by bone morphogenetic protein 2 via SMAD1. SFRP3 blocked the interaction between FZD7 and WNT10B to decrease BeWo cell migration, which corroborated the elevated BeWo cell migration when cocultured with decidualized and SFRP3-knockdown T-HESC monolayer. Our results suggest that GCM1 up-regulates EVT cell migration through WNT10B and FZD7, which is negatively modulated by decidual SFRP3.-Wang, L.-J., Lo, H.-F., Lin, C.-F., Ng, P.-S., Wu, Y.-H., Lee, Y.-S., Cheong, M.-L., Chen, H. SFRP3 negatively regulates placental extravillous trophoblast cell migration mediated by the GCM1-WNT10B-FZD7 axis.

Endogenous IL-10 maintains immune tolerance but IL-10 gene transfer exacerbates autoimmune cholangitis.

The immunomodulatory effect of IL-10 as an immunosuppressive and anti-inflammatory cytokine is well known. Taking advantage of our established mouse model of autoimmune cholangitis using 2-octynoic acid conjugated ovalbumin (2-OA-OVA) induction, we compared liver pathology, immune cell populations and antimitochondrial antibodies between IL-10 knockout and wild type mice immunized with 2-OA-OVA. At 10 weeks post immunization, portal inflammation and fibrosis were more severe in 2-OA-OVA immunized IL-10 knockout mice than in wild type mice. This was accompanied by significant higher levels of collagen I and III expression, T, NK and NKT subsets in liver and IgG anti-mitochondrial autoantibodies (AMAs) compared to 2-OA-OVA immunized wild type mice, suggesting that endogenous IL-10 is necessary for the maintenance of immune tolerance in primary biliary cholangitis (PBC). Further, we investigated whether administration of exogenous IL-10 could prevent PBC by administration of IL-10 expressing recombinant adeno-associated virus (AAV-IL-10) either 3 days before or 3 weeks after the establishment of liver pathology. Interestingly, administration of AAV-IL-10 resulted in increased liver inflammation and fibrosis, accompanied by increases in IFN-γ in liver CD4+ T cell, granzyme B, FasL, and CD107a in liver CD8+ T and NKT cells, and granzyme B and FasL in liver NK cells of AAV-IL-10 administered mice compared with control mice. Furthermore, administration of AAV-IL-10 significantly increased levels of proinflammatory cytokines and chemokines (IFN-γ, TNF-α, CXCL9 and CXCL10) and collagen I and III production in naïve mice, together with increase in immune cell infiltration and collagen deposition in the liver, suggesting a role of IL-10 in fibrosis. In conclusion, our data demonstrate that endogenous IL-10 is critical in the maintenance of immune tolerance but exogenous administration of IL-10 exacerbates liver inflammation and fibrosis. Furthermore, the distinctive presence of inflammatory immune cell populations and collagen expression in AAV-IL-10 treated naïve mice cautions against the clinical use of exogenous IL-10 in patients with autoimmune cholangitis.

New insights into the regulation of placental growth factor gene expression by the transcription factors GCM1 and DLX3 in human placenta.

Expression of placental growth factor (PGF) is closely associated with placental perfusion in early pregnancy. PGF is primarily expressed in placental trophoblasts, and its expression decreases in preeclampsia, associated with placental hypoxia. The transcription factors glial cells missing 1 (GCM1) and metal-regulatory transcription factor 1 (MTF1) have been implicated in the regulation of PGF gene expression through regulatory elements upstream and downstream of the PGF transcription start site, respectively. Here, we clarified the mechanism underlying placenta-specific PGF expression. We demonstrate that GCM1 up-regulates PGF expression through three downstream GCM1-binding sites (GBSs) but not a previously reported upstream GBS. Interestingly, we also found that these downstream GBSs also harbor metal-response elements for MTF1. Surprisingly, however, we observed that MTF1 is unlikely to regulate PGF expression in the placenta because knockdown or overexpression of GCM1, but not MTF1, dramatically decreased PGF expression or reversed the suppression of PGF expression under hypoxia, respectively. We also demonstrate that another transcription factor, Distal-less homeobox 3 (DLX3), interacts with the DNA-binding domain and the first transactivation domain of GCM1 and that this interaction inhibits GCM1-mediated PGF expression. Moreover, the GCM1-DLX3 interaction interfered with CREB-binding protein-mediated GCM1 acetylation and activation. In summary, we have identified several GBSs in the PGF promoter that are highly responsive to GCM1, have demonstrated that MTF1 does not significantly regulate PGF expression in placental cells, and provide evidence that DLX3 inhibits GCM1-mediated PGF expression. Our findings revise the mechanism for GCM1- and DLX3-mediated regulation of PGF gene expression.

Emergency percutaneous nephrostomy versus emergency percutaneous nephrolithotomy in patients with sepsis associated with large uretero-pelvic junction stone impaction: a randomized controlled trial

ABSTRACT Introduction A randomized trial was conducted prospectively to evaluate the efficacy, related complications, and convalescence of emergency percutaneous nephrolithotomy compared to percutaneous nephrostomy for decompression of the collecting system in cases of sepsis associated with large uretero-pelvic junction stone impaction. Materials and Methods The inclusion criteria included a WBC count of 10.000/mm3 or more and/or a temperature of 38°C or higher. Besides, all enrolled patients should maintain stable hemodynamic status and proper organ perfusions. A total of 113 patients with large, obstructive uretero-pelvic junction stones and clinical signs of sepsis completed the study protocol. Of those, 56 patients were placed in the emergency percutaneous nephrostomy group, while the other 57 patients were part of the percutaneous nephrolithotomy group. The primary end point was the time until normalization of white blood cells (WBC) at a count of 10.000/mm3 or less, and a temperature of 37.4°C or lower. The secondary end points included the comparison of analgesic consumption, length of stay, and related complications. Statistical analysis was performed using SPSS® version 14.0.1. The Mann-Whitney U test, chi-square test, and Fisher’s exact test were used as appropriate. Results The length of hospital stays (in days) was 10.09±3.43 for the emergency percutaneous nephrostomy group and 8.18±2.72 for the percutaneous nephrolithotomy group. This set of data noted a significant difference between groups. There was no difference between groups in regard to white blood cell count (in mm3), time to normalization of white blood cell count (in days), body temperature (in ºC), time to normalization of body temperature (in days), C-reactive proteins (in mg/dL), time taken for C-reactive proteins to decrease over 25% (in days), procalcitonin (in ng/mL), or complication rates. Conclusions This study confirms that emergency percutaneous nephrolithotomy may be as safe as early percutaneous nephrolithotomy in a selected low risk patients with sepsis-associated large, obstructive stone.

Emergency percutaneous nephrostomy versus emergency percutaneous nephrolithotomy in patients with sepsis associated with large uretero-pelvic junction stone impaction: a randomized controlled trial.

INTRODUCTION: A randomized trial was conducted prospectively to evaluate the efficacy, related complications, and convalescence of emergency percutaneous nephrolithotomy compared to percutaneous nephrostomy for decompression of the collecting system in cases of sepsis associated with large uretero-pelvic junction stone impaction. MATERIALS AND METHODS: The inclusion criteria included a WBC count of 10.000/mm3 or more and/or a temperature of 38°C or higher. Besides, all enrolled patients should maintain stable hemodynamic status and proper organ perfusions. A total of 113 patients with large, obstructive uretero-pelvic junction stones and clinical signs of sepsis completed the study protocol. Of those, 56 patients were placed in the emergency percutaneous nephrostomy group, while the other 57 patients were part of the percutaneous nephrolithotomy group. The primary end point was the time until normalization of white blood cells (WBC) at a count of 10.000/mm3 or less, and a temperature of 37.4°C or lower. The secondary end points included the comparison of analgesic consumption, length of stay, and related complications. Statistical analysis was performed using SPSS® version 14.0.1. The Mann-Whitney U test, chi-square test, and Fisher's exact test were used as appropriate. RESULTS: The length of hospital stays (in days) was 10.09±3.43 for the emergency percutaneous nephrostomy group and 8.18±2.72 for the percutaneous nephrolithotomy group. This set of data noted a significant difference between groups. There was no difference between groups in regard to white blood cell count (in mm3), time to normalization of white blood cell count (in days), body temperature (in ºC), time to normalization of body temperature (in days), C-reactive proteins (in mg/dL), time taken for C-reactive proteins to decrease over 25% (in days), procalcitonin (in ng/mL), or complication rates. CONCLUSIONS: This study confirms that emergency percutaneous nephrolithotomy may be as safe as early percutaneous nephrolithotomy in a selected low risk patients with sepsis-associated large, obstructive stone.

Association of dysfunctional synapse defective 1 (SYDE1) with restricted fetal growth - SYDE1 regulates placental cell migration and invasion.

The transcription factor glial cells missing 1 (GCM1) regulates trophoblast differentiation and function during placentation. Decreased GCM1 expression is associated with pre-eclampsia, suggesting that abnormal expression of GCM1 target genes may contribute to the pathogenesis of pregnancy complications. Here we identified a novel GCM1 target gene, synapse defective 1 (SYDE1), which encodes a RhoGAP that is highly expressed in human placenta, and demonstrated that SYDE1 promotes cytoskeletal remodelling and cell migration and invasion. Importantly, genetic ablation of murine Syde1 results in small fetuses and placentas with aberrant phenotypes in the placental-yolk sac barrier, maternal-trophoblast interface, and placental vascularization. Microarray analysis revealed altered expression of renin-1, angiotensin I converting enzyme 2, angiotensin II type 1a receptor, and membrane metalloendopeptidase of the renin-angiotensin system in Syde1-knockout placenta, which may compensate for the vascular defects to maintain normal blood pressure. As pregnancy proceeds, growth restriction of the Syde1-/- fetuses and placentas continues, with elevated expression of the Syde1 homologue Syde2 in placenta. Syde2 may compensate for the loss of Syde1 function because SYDE2, but not the GAP-dead SYDE2 mutant, reverses migration and invasion activities of SYDE1-knockdown JAR trophoblast cells. Clinically, we further detected decreased SYDE1 expression in preterm and term IUGR placentas compared with gestational age-matched controls. Our study suggests a novel mechanism for GCM1 and SYDE1 in regulation of trophoblast cell migration and invasion during placental development and that decreased SYDE1 expression is associated with IUGR. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.