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Type 2 diabetes, insulin resistance, and obesity are strongly associated and are a major health problem worldwide. Obesity largely results from a sustained imbalance between energy intake and expenditure. Therapeutic approaches targeting metabolic rate may counteract body weight gain and insulin resistance. Bone morphogenic protein 7 (BMP7) has proven to enhance energy expenditure by inducing non-shivering thermogenesis in short-term studies in mice treated with the recombinant protein or adenoviral vectors encoding BMP7 . To achieve long-term BMP7 effects, the use of adeno-associated viral (AAV) vectors would provide sustained production of the protein after a single administration. Here, we demonstrated that treatment of high-fat-diet-fed mice and ob/ob mice with liver-directed AAV-BMP7 vectors enabled a long-lasting increase in circulating levels of this factor. This rise in BMP7 concentration induced browning of white adipose tissue (WAT) and activation of brown adipose tissue, which enhanced energy expenditure, and reversed WAT hypertrophy, hepatic steatosis, and WAT and liver inflammation, ultimately resulting in normalization of body weight and insulin resistance. This study highlights the potential of AAV-BMP7-mediated gene therapy for the treatment of insulin resistance, type 2 diabetes, and obesity., Competing Interests: The authors declare no competing interests., (© 2022 The Authors.)

Aggregation of α-synuclein is associated with neurodegeneration and a hallmark pathology in synucleinopathies. These aggregates are thought to function as prion-like particles where the conformation of misfolded α-synuclein determines the traits of the induced pathology, similar to prion diseases. Still, little is known about the molecular targets facilitating the conformation-specific biological effects, but their identification could form the basis for new therapeutic interventions. High-throughput screening of annotated compound libraries could facilitate mechanistic investigation by identifying targets with impact on α-synuclein aggregation. To this end, we developed a FRET-based cellular reporter in HEK293T cells, with sensitivity down to 6.5 nM α-synuclein seeds. Using this model system, we identified GF109203X, SB202190, and SB203580 as inhibitors capable of preventing induction of α-synuclein aggregation via inhibition of p38 MAPK and PKC, respectively. We further investigated the mechanisms underlying the protective effects and found alterations in the endo-lysosomal system to be likely candidates of the protection. We found the changes did not stem from a reduction in uptake but rather alteration of lysosomal abundance and degradative capacity. Our findings highlight the value high-throughput screening brings to the mechanistic investigation of α-synuclein aggregation while simultaneously identifying novel therapeutic compounds., (© 2021. The Author(s).)

Purpose: High-pressure balloon dilatation (HPBD) of the ureterovesical junction with double-J stenting is a minimally invasive alternative to ureteral reimplantation or cutaneous ureterostomy for first-line surgical treatment of primary obstructive megaureter (POM). The aim of our study was to identify the risk factors associated with the need for secondary procedures due to HPBD failure., Methods: Prospective data were collected from patients who underwent HPBD for POM between 2007 and 2021 at a single institution. The collected data included patient demographics, diagnostic modalities, surgical details, results, and follow-up. Multivariate logistic regression analysis was performed., Results: Fifty-five ureters underwent HPBD for POM in 50 children, with a median age of 6.4 months (IQR: 4.5-13.8). Nineteen patients (37.25%) underwent secondary ureteric reimplantation, with a median of 9.8 months after primary HBPD (95% CI 6.2-9.9). The median follow-up was 29.4 months (IQR: 17.4-71). Independent risk factors for redo-surgery in a multivariate logistic regression model were: progressive ureterohydronephrosis (OR = 7.8; 95% CI 0.77-78.6) and early removal of the double-J stent. A risk reduction of 7% (95% CI 2.2%-11.4%) was observed per extra-day of catheter maintenance. The optimal cut-off point is 55 days, ROC curve area: 0.77 (95% CI 0.62-0.92). Gender, distal ureteral diameter, pelvis diameter, dilatation balloon diameter and preoperative differential renal function did not affect the need for reimplantation., Conclusions: The use of a double-J stent for at least 55 days seems to avoid the need for a secondary procedure. Therefore, we recommend removing the double-J catheter at least 2 months after the HBPD., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Malaria liver stage infection is an obligatory parasite development step and represents a population bottleneck in Plasmodium infections, providing an advantageous target for blocking parasite cycle progression. Parasite development inside hepatocytes implies a gross cellular insult evoking innate host responses to counteract intra-hepatocytic infection. Using primary hepatocyte cultures, we investigated the role of Kupffer cell-derived hepatocyte growth factor (HGF) in malaria liver stage infection. We found that Kupffer cells from Plasmodium -infected livers produced high levels of HGF, which trigger apoptosis of infected hepatocytes through a mitochondrial-independent apoptosis pathway. HGF action in infected hepatocyte primary cultures results in a potent reduction of parasite yield by specifically sensitizing hepatocytes carrying established parasite exo-erythrocytic forms to undergo apoptosis. This apoptosis mechanism is distinct from cell death that is spontaneously induced in infected cultures and is governed by Fas signaling modulation through a mitochondrial-dependent apoptosis pathway. This work indicates that HGF and Fas signaling pathways are part of an orchestrated host apoptosis response that occurs during malaria liver stage infection, decreasing the success of infection of individual hepatocytes. Our results raise the hypothesis that paracrine signals derived from Kupffer cell activation are implicated in directing death of hepatocytes infected with the malaria parasite.

Even if vesicoureteral reflux is a common condition in children, there are no guidelines about the best therapeutic approach. This study aims to compare the results of endoscopic injection and ureteral reimplantation in children with grade III, IV and V VUR. A multicenter retrospective study included children with grade III, IV and V VUR treated from 2003 to 2018 at three Departments of Pediatric Surgery. Patients were divided into Group A (endoscopic injections) and Group B (anti-reflux surgery), B1 (open, OUR), B2 (laparoscopic, LUR) and B3 (robot-assisted laparoscopic RALUR). Follow-up was at least 5 years. 400 patients were included, 232 (58%) in group A and 168 (42%) in group B. Mean age at surgery was 38.6 months [3.1–218.7]. Mean follow-up was 177.8 months [60–240]. Group A had shorter operative time than group B (P < 0.01); lower analgesic requirement (p < 0.05), shorter hospital stay (P < 0.05) and lower overall costs (p < 0.05), but higher postoperative PNPs (p < 0.01), lower success rate (p < 0.01) and higher redo-surgery percentage (p < 0.01). No differences in terms of postoperative complications, success rate and mean radiation exposure between the two groups. Endoscopy is associated with shorter operative time, shorter hospitalization and lower cost, also in case of multiple injections. Recurrence rate after surgery is lower meaning lower rate of re-hospitalization and radiation exposure for children. [ABSTRACT FROM AUTHOR]

Decidual macrophages residing at the maternal-fetal interface have been recognized as pivotal factors for maintaining normal pregnancy; however, they are also key target cells of Toxoplasma gondii (T. gondii) in the pathology of T. gondii-induced adverse pregnancy. Trem2, as a functional receptor on macrophage surface, recognizes and binds various kinds of pathogens. The role and underlying mechanism of Trem2 in T. gondii infection remain elusive. In the present study, we found that T. gondii infection downregulated Trem2 expression and that Trem2-/- mice exhibited more severe adverse pregnancy outcomes than wildtype mice. We also demonstrated that T. gondii infection resulted in increased decidual macrophages, which were significantly reduced in the Trem2-/- pregnant mouse model as compared to wildtype control animals. We further described the inhibited proliferation, migration, and invasion functions of trophoblast cell by T. gondii antigens through macrophages as an "intermediate bridge", while this inhibition can be rescued by Trem2 agonist HSP60. Concurrently, Trem2 deficiency in bone marrow-derived macrophages (BMDMs) heightened the inhibitory effect of TgAg on the migration and invasion of trophoblast cells, accompanied by higher pro-inflammatory factors (IL-1β, IL-6 and TNF-α) but a lower chemokine (CXCL1) in T. gondii antigens-treated BMDMs. Furthermore, compelling evidence from animal models and in vitro cell experiments suggests that T. gondii inhibits the Trem2-Syk-PI3K signaling pathway, leading to impaired function of decidual macrophages. Therefore, our findings highlight Trem2 signaling as an essential pathway by which decidual macrophages respond to T. gondii infection, suggesting Trem2 as a crucial sensor of decidual macrophages and potential therapeutic target in the pathology of T. gondii-induced adverse pregnancy. Author summary: T. gondii is a critically important intracellular protozoan that is a major cause of adverse pregnancy outcomes in humans and livestock. The pathology of adverse pregnancy induced by T. gondii involves the dysfunction of decidual macrophages. Trem2, a functional immune receptor on the surface of decidual macrophages, governs its survival and phagocytosis. Here, we sought to elucidate whether Trem2 signaling is involved in the pathology of T. gondii-induced adverse pregnancy. We found that T. gondii infection led to the downregulation of Trem2 expression in macrophages, both in vivo and in vitro. Trem2-/- mice exhibit more severe adverse pregnancy outcomes after T. gondii infection. We further described the inhibited proliferation, migration, and invasion functions of trophoblast cell by T. gondii antigens through macrophages as an "intermediate bridge", while this inhibition can be rescued by Trem2 agonist HSP60. In parallel, Trem2 deficiency in BMDMs heightened the inhibitory effect of TgAg on the migration and invasion of trophoblast cells. Our work uncovers an important factor involved in the pathological mechanism of T. gondii-induced adverse pregnancy, and research on Trem2 may provide new preventive and therapeutic targets for toxoplasmosis. [ABSTRACT FROM AUTHOR]

Nondestructive methods are a fast and accurate way to obtain information about the mechanical properties of plywood panels. The objective was to determine the modulus of rupture and compare the modulus of elasticity (MOE) in plywood boards made with Pinus spp. and Eucalyptus urograndis using the destructive method of three-point static bending and the nondestructive method of ultrasound in parallel and perpendicular directions, as well as in complete board and test specimens, both with the ultrasound method and the correlation between the variables studied. The plywood boards evaluated were 18, 25 and 30 mm nominal thickness. Five structures were evaluated using pine and pine–eucalyptus veneers. Three boards were collected per structure, and 28 specimens were made from each board (14 in a parallel direction and 14 in a perpendicular direction). The elastic modulus was determined by the ultrasound method in complete plywood boards and in specimens obtained from them using the IML Micro Hammer® equipment and through the conventional bending test, carried out in an Instron® universal mechanical testing machine. The Tukey test of means (p < 0.05) shows that in the nominal thickness of 18 mm, the modulus of elasticity by ultrasound was lower compared to the result obtained by static bending in four of the five structures in the perpendicular direction and lower in all the structures evaluated in the parallel direction; while in the nominal thickness of 25 and 30 mm, it was greater in all structures and in both directions. The results of static bending by ultrasound, in complete boards and specimens, show that the only significant difference (p < 0.05) occurs in the nominal thickness of 30 mm in the treatment made with pine–eucalyptus with urea formaldehyde resin being lower in the parallel direction and in complete boards The correlation between the modulus of elasticity determined on specimens using the nondestructive method and the destructive method was r = 0.75 and Pr < 0.05; while comparing the nondestructive method on test specimens and complete plywood panels, r = 0.73 and Pr < 0.05 were obtained. It is concluded that the mechanical bending property of plywood boards can be characterized by the ultrasound method. [ABSTRACT FROM AUTHOR]

Purpose: The aim of our study is to compare the outcomes of open and laparoscopic pyeloplasty in children less than 12 months of age., Patients and Methods: We reviewed all medical charts of patients less than 12 months old who underwent pyeloplasty from January 2007 to February 2013. We divided them in two groups: Open pyeloplasty (OP) and laparoscopic pyeloplasty (LP). The following data were analyzed: age, sex, weight, US measurements, operative time, hospital stay, complications, and success rate. Quantitative data were analyzed with the Student t test or Mann-Whitney U test, and chi-square test or Fisher test for qualitative data., Results: Fifty-eight patients (46 boys and 12 girls) with a mean age of 4.66 months (±3.05) were included. Mean age was 4.25 months and 5.15 months in OP and LP group respectively. Mean weight was 6.78 kg and 7.02 kg in OP and LP groups. There were no statistical differences in age, weight, and sex between OP and LP groups. There were no statistical differences in preoperative ultrasonography measurements. Mean posterior-anterior (PA) pelvis diameter was 28.57 mm and 23.94 mm in OP and LP groups, respectively. Mean calices diameter were 10.86 mm and 10.96 mm in OP and LP groups, respectively. Mean operative time was 129.53 minutes in the OP group and 151.92 minutes in the LP group with statistical differences (P=0.018). Mean hospital stay was 6.34 days in the OP group and 3.46 in the LP group with statistical differences (P<0.05). No intraoperative and postoperative complications were found in either group. Hydronephrosis improved in all patients, and no patient needed a repeated pyeloplasty., Conclusion: The laparoscopic approach of Anderson-Hynes pyeloplasty in patients less than 12 months old is a safe procedure with the same outcomes as the open approach.

Plasmodium liver stage infection is a target of interest for the treatment of and vaccination against malaria. Here we used forward genetics to search for mechanisms underlying natural host resistance to infection and identified triggering receptor expressed on myeloid cells 2 (TREM2) and MHC class II molecules as determinants of Plasmodium berghei liver stage infection in mice. Locus belr1 confers resistance to malaria liver stage infection. The use of newly derived subcongenic mouse lines allowed to map belr1 to a 4-Mb interval on mouse chromosome 17 that contains the Trem2 gene. We show that Trem2 expression in the nonparenchymal liver cells closely correlates with resistance to liver stage infection, implicating TREM2 as a mediator of the belr1 genetic effect. Trem2-deficient mice are more susceptible to liver stage infection than their WT counterparts. We found that Kupffer cells are the principle cells expressing TREM2 in the liver, and that Trem2(-/-) Kupffer cells display altered functional activation on exposure to P. berghei sporozoites. TREM2 expression in Kupffer cells contributes to the limitation of parasite expansion in isolated hepatocytes in vitro, potentially explaining the increased susceptibility of Trem2(-/-) mice to liver stage infection. The MHC locus was also found to control liver parasite burden, possibly owing to the expression of MHC class II molecules in hepatocytes. Our findings implicate unexpected Kupffer-hepatocyte cross-talk in the control Plasmodium liver stage infection and demonstrate that TREM2 is involved in host responses against the malaria parasite.

Objective: To report our experience of laparoscopic heminephroureterectomy (Hnu) in pediatric patients with duplex anomalies, in comparison to open surgery., Patients and Methods: Retrospective review of data from patients who underwent Hnu from 2005 to 2008 was performed. The patients were divided into two groups: laparoscopic (LHnu) and open surgery (OHnu). Laparoscopic surgery was performed by transperitoneal approach in majority of cases. Open surgery was performed by retroperitoneal approach in all cases., Results: Group LHnu: nine patients (8 females, 1 male) with median age of 14 months (range 3-205). Transperitoneal approach was performed in eight patients. Mean operative time was 182 min (CI 95% 146-217). No conversion to open surgery was necessary and there were no complications. Mean hospital stay was 2.44 days (CI 95% 1.37-3.52). Group OHnu: eight patients (3 females, 5 males) underwent nine heminephrectomies at median age of 6.9 months (range 1-12). Mean operating time was 152 min (CI 95% 121-183). There were no complications and mean hospital stay was 4.38 (CI 95% 2.59-6.16) days. Statistical analysis showed no statistically significant difference (P>0.05) in operating time between groups while mean hospital stay was significant (P=0.021)., Conclusion: The laparoscopic approach is feasible, safe, reduces hospital stay, does not increase operating time and has better cosmetic results. We believe this should be the first option for heminephrectomy., (Copyright © 2009 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Purpose: The potential efficacy of metformin in breast cancer (BC) has been hotly discussed but never conclusive. This genetics-based study aimed to evaluate the relationships between metformin targets and BC risk. Methods: Metformin targets from DrugBank and genome-wide association study (GWAS) data from IEU OpenGWAS and FinnGen were used to investigate the breast cancer (BC)-metformin causal link with various Mendelian Randomization (MR) methods (e.g., inverse-variance-weighting). The genetic association between type 2 diabetes (T2D) and the drug target of metformin was also analyzed as a positive control. Sensitivity and pleiotropic tests ensured reliability. Results: The primary targets of metformin are PRKAB1, ETFDH and GPD1L. We found a causal association between PRKAB1 and T2D (odds ratio [OR] 0.959, P = 0.002), but no causal relationship was observed between metformin targets and overall BC risk (PRKAB1: OR 0.990, P = 0.530; ETFDH: OR 0.986, P = 0.592; GPD1L: OR 1.002, P = 0.806). A noteworthy causal relationship was observed between ETFDH and estrogen receptor (ER)-positive BC (OR 0.867, P = 0.018), and between GPD1L and human epidermal growth factor receptor 2 (HER2)-negative BC (OR 0.966, P = 0.040). Other group analyses did not yield positive results. Conclusion: The star target of metformin, PRKAB1, does not exhibit a substantial causal association with the risk of BC. Conversely, metformin, acting as an inhibitor of ETFDH and GPD1L, may potentially elevate the likelihood of developing ER-positive BC and HER2-negative BC. Consequently, it is not advisable to employ metformin as a standard supplementary therapy for BC patients without T2D. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency is very common worldwide, particularly in old age, when people are at the highest risk of the negative adverse consequences of hypovitaminosis D. Additionally to the recognized functions in the regulation of calcium absorption, bone remodeling, and bone growth, vitamin D plays a key role as a hormone, which is supported by various enzymatic, physiological, metabolic, and pathophysiological processes related to various human organs and systems. Accruing evidence supports that vitamin D plays a key role in pancreatic islet dysfunction and insulin resistance in type 2 diabetes. From an epidemiological viewpoint, numerous studies suggest that the growing incidence of type 2 diabetes in humans may be linked to the global trend of prevalent vitamin D insufficiency. In the past, this association has raised discussions due to the equivocal results, which lately have been more convincing of the true role of vitamin D supplementation in the prevention of incident type 2 diabetes. Most meta-analyses evaluating this role have been conducted in adults or young older persons (50–60 years old), with only one focusing on older populations, even if this is the population at greater risk of both hypovitaminosis D and type 2 diabetes. Therefore, we conducted an update of the previous systematic review and meta-analysis examining whether hypovitaminosis D (low serum 25OHD levels) can predict incident diabetes in prospective longitudinal studies among older adults. We found that low 25OHD was associated with incident diabetes in older adults even after adjusting for several relevant potential confounders, confirming and updating the results of the only previous meta-analysis conducted in 2017. [ABSTRACT FROM AUTHOR]

This study aims to assess the effectiveness of water-based formulations featuring m-2HEAOL and talc particles in deep drawing applications. The coefficient of friction (COF) was measured through bending under tension (BUT) tests, while the interaction mechanism between protic ionic liquid (PIL) and talc particles was analysed using FTIR, XPS, and TGA analyses. The results indicate that the formulation containing 8 wt% PIL and 0.5 wt% talc exhibited the best lubricating performance. This was due to the interaction of the PIL oleate molecules with the Mg found in the talc basal layer, which enhanced the cleavage capacity of this mineral, ultimately improving the lubricity of the formulation. [ABSTRACT FROM AUTHOR]

Obesity has become a pandemic, as currently more than half a billion people worldwide are obese. The etiology of obesity is multifactorial, and combines a contribution of hereditary and behavioral factors, such as nutritional inadequacy, along with the influences of environment and reduced physical activity. Two types of adipose tissue widely known are white and brown. While white adipose tissue functions predominantly as a key energy storage, brown adipose tissue has a greater mass of mitochondria and expresses the uncoupling protein 1 (UCP1) gene, which allows thermogenesis and rapid catabolism. Even though white and brown adipocytes are of different origin, activation of the brown adipocyte differentiation program in white adipose tissue cells forces them to transdifferentiate into "beige" adipocytes, characterized by thermogenesis and intensive lipolysis. Nowadays, researchers in the field of small molecule medicinal chemistry and gene therapy are making efforts to develop new drugs that effectively overcome insulin resistance and counteract obesity. Here, we discuss various aspects of white-to-beige conversion, adipose tissue catabolic re-activation, and non-shivering thermogenesis. [ABSTRACT FROM AUTHOR]

LPS is a strong stimulator of the innate immune system and inducer of B lymphocyte activation. Two TLRs, TLR4 and RP105 (CD180), have been identified as mediators of LPS signaling in murine B cells, but little is known about genetic factors that are able to control LPS-induced cell activation. We performed a mouse genome-wide screen that aside from identifying a controlling locus mapping in the TLR4 region (logarithm of odds score, 2.77), also revealed that a locus closely linked to the MHC region (logarithm of odds score, 3.4) governed B cell responsiveness to LPS stimulation. Using purified B cells obtained from MHC congenic strains, we demonstrated that the MHC(b) haplotype is accountable for higher cell activation, cell proliferation, and IgM secretion, after LPS stimulation, when compared with the MHC(d) haplotype. Furthermore, B cells from MHC class II(-/-) mice displayed enhanced activation and proliferation in response to LPS. In addition, we showed that the MHC haplotype partially controls expression of RP105 (a LPS receptor molecule), following a pattern that resembles the LPS responsiveness phenotype. Together, our results strongly suggest that murine MHC class II molecules play a role in constraining the B cell response to LPS and that genetic variation at the MHC locus is an important component in controlling B cell responsiveness to LPS stimulation. This work raises the possibility that constraining of B cell responsiveness by MHC class II molecules may represent a functional interaction between adaptive and innate immune systems.

Adipose tissue is a multifunctional organ that regulates many physiological processes such as energy homeostasis, nutrition, the regulation of insulin sensitivity, body temperature, and immune response. In this review, we highlight the relevance of the different mediators that control adipose tissue activity through a systematic review of the main players present in white and brown adipose tissues. Among them, inflammatory mediators secreted by the adipose tissue, such as classical adipokines and more recent ones, elements of the immune system infiltrated into the adipose tissue (certain cell types and interleukins), as well as the role of intestinal microbiota and derived metabolites, have been reviewed. Furthermore, anti-obesity mediators that promote the activation of beige adipose tissue, e.g., myokines, thyroid hormones, amino acids, and both long and micro RNAs, are exhaustively examined. Finally, we also analyze therapeutic strategies based on those mediators that have been described to date. In conclusion, novel regulators of obesity, such as microRNAs or microbiota, are being characterized and are promising tools to treat obesity in the future. [ABSTRACT FROM AUTHOR]

Copyright of Osmangazi Journal of Medicine / Osmangazi Tip Dergisi is the property of Eskisehir Osmangazi University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The improvement of human living conditions has led to an increase in average life expectancy, creating a new social and medical problem—aging, which diminishes the overall quality of human life. The aging process of the body begins with the activation of effector signaling pathways of aging in cells, resulting in the loss of their normal functions and deleterious effects on the microenvironment. This, in turn, leads to chronic inflammation and similar transformations in neighboring cells. The cumulative retention of these senescent cells over a prolonged period results in the deterioration of tissues and organs, ultimately leading to a reduced quality of life and an elevated risk of mortality. Among the most promising methods for addressing aging and age-related illnesses are pharmacological, genetic, and cellular therapies. Elevating the activity of aging-suppressing genes, employing specific groups of native and genetically modified cells, and utilizing senolytic medications may offer the potential to delay aging and age-related ailments over the long term. This review explores strategies and advancements in the field of anti-aging therapies currently under investigation, with a particular emphasis on gene therapy involving adeno-associated vectors and cell-based therapeutic approaches. [ABSTRACT FROM AUTHOR]

Copyright of Cirugía Pediátrica (English Edition) is the property of Sociedad Espanola de Cirurgia Pediatrica and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: Bladder lesions like urothelial carcinoma are rare in the first two decades of life. A biopsy of the bladder or urinary cytological examination is seldom required. Gross painless hematuria is the most relevant clinical syndrome. Methods: A retrospective analysis of surgical pathology records collected between 1984 and 2014 at our institution was performed in a search for cases of urothelial neoplasms originating within the urinary bladder in pediatric patients. Diagnoses were confirmed based on pathologic examination using the 2004 World Health Organization (WHO) classification system. We selected keywords such as bladder neoplasia, bladder lesion, urothelial neoplasia, rhabdomyosarcoma, and children. In addition, we describe clinical presentation and diagnostic procedures as well as treatment and follow-up of two patients. A review of the literature was performed to analyze recommendations concerning diagnostic staging, treatment, and follow-up examinations as well as surveillance of urothelial tumors in the pediatric population. Results: Screening the pathology database of the Institute of Medical Genetics and Pathology of the University Hospital Basel between 1988 and 2014 yielded 287 samples involving the urinary bladder, 110 autopsies, 135 biopsies, and 42 cytology specimens. Of these, most samples originated from malformations and inflammation. Only five were tumors: two were urothelial tumors and three were rhabdomyosarcomas. The majority of specimens comprised resections of the diverticula or distal ureter. Our case reports include two patients with a urothelial tumor. Among the urothelial tumors, one was a papillary urothelial neoplasm of low malignant potential (PUNLMP). Painless hematuria was the directing clinical symptom. The tumor was investigated by FISH, and a 9p21 deletion was found. The second tumor-like lesion was a fibroepithelial polyp arising from the bladder neck. Conclusions: Bladder tumors in children are rare and mostly consist of urothelial and mesenchymal neoplasms. Rhabdomyosarcoma is the most common malignant bladder tumor in childhood. Similar to adult urothelial neoplasms, the loss of 9p21 is also implicated in urothelial neoplasms in childhood. Despite an increasing number of case reports and small series published within the last 2 decades, general treatment protocols including recommendations for staging, tumor markers, and follow-up examinations are still not yet available for this tumor entity in the pediatric population. [ABSTRACT FROM AUTHOR]

Objective: To compare the long-term effectiveness, complications, and outcomes of primary obstructive megaureter (POM) treated by endoscopic balloon dilation under fluoroscopic guidance versus not using radioscopy during the procedure. Patients and methods: A comparative study between POM cases treated at our institution by endoscopic balloon dilation (EBD) under fluoroscopic guidance (FG) (n = 43) vs no fluoroscopic guidance (NFG) (n = 48) between the years 2004 and 2018 was conducted. The procedure in FG consisted of performing a retrograde pyelography before dilation. Then, a guidewire is introduced to the renal pelvis, and the dilation of the vesicoureteral junction is performed using high-pressure balloon catheters under fluoroscopic vision. Finally, a double-J stent is placed between the renal pelvis and bladder. The procedure in NFG was performed exclusively under cystoscopic vision without radiological exposure. Complications, outcomes, and success rates were analyzed using Spearman's correlation test. Mean follow-up was 12.5 ± 2.2 years in FG and 6.4 ± 1.3 years in NFG. Results: MAG-3 showed significant differences in renal drainage before and after endoscopic treatment in both groups (p < 0.001 T-test). Statistical analysis did not reveal differences between groups in initial technical failure (r: − 0.035, p = 0.74), early postoperative complications (r: − 0.029, p = 0.79), secondary VUR (r: 0.033, p = 0.76), re-stenosis (r: 0.022, p = 0.84), long-term ureteral reimplantation (r: 0.065, p = 0.55), and final outcome (r: − 0.054, p = 0.61). The endoscopic approach of POM had a long-term success rate of 86.5% in FG VS 89.6% in NFG. Conclusions: Endoscopic balloon dilation of POM can be done with no radiation exposure with similar results, effectiveness, and outcomes. [ABSTRACT FROM AUTHOR]

Objective: The aim of our study is to compare long-term outcome of endoscopic treatment of VUR using PPC or Dx/HA. Patients and methods: From October 2014 to April 2017 patients with VUR grades from 3 to 5 that needed endoscopic treatment were eligible for this RCT. Patients were randomized in two groups: PPC and Dx/HA. A VCUG was performed at 6 months; if VUR > 3 was still present a second ET was performed. We included for this long-term follow-up study those patients that were successfully treated at short-term follow-up. At 36 months postoperative VCUG was performed to assess outcome. Success was considered if postoperative VUR grade was 0 at 36 months, and there was no ureteral obstruction. Results: In the previous study, 60/73 ureters were successfully treated in 36/44 patients, and then we have analyzed 60 ureters in 36 patients. Three patients were lost in long-term follow-up, and then we analyzed 57 ureters in 33 patients divided. PPC group 18 patients (28 ureters); and Dx/HA group 15 patients (29 ureters). After 3 years of follow-up the VCUG showed a success rate of 26/28 of RU in PPC and 26/29 of DX/HA. Two RU in PPC group had ureteral obstruction, and then the successful rate for PPC group dropped to 24/28. The overall successful rate at long-term was 72.7% of the RU in PPC group and 70.3% in Dx/HA group. Conclusion: PPC and Dx/HA has similar long-term outcome in VUR resolution, but ureteral obstruction could be present at long-term follow-up in PPC group. [ABSTRACT FROM AUTHOR]

Maintaining systemic homeostasis requires the coordination of different organs and tissues in the body. Our bodies rely on complex inter-organ communications to adapt to perturbations or changes in metabolic homeostasis. Consequently, the liver, muscle, and adipose tissues produce and secrete specific organokines such as hepatokines, myokines, and adipokines in response to nutritional and environmental stimuli. Emerging evidence suggests that dysregulation of the interplay of organokines between organs is associated with the pathophysiology of obesity and type 2 diabetes (T2D). Strategies aimed at remodeling organokines may be effective therapeutic interventions. Diet modification and exercise have been established as the first-line therapeutic intervention to prevent or treat metabolic diseases. This review summarizes the current knowledge on organokines secreted by the liver, muscle, and adipose tissues in obesity and T2D. Additionally, we highlighted the effects of diet/nutrition and exercise on the remodeling of organokines in obesity and T2D. Specifically, we investigated the ameliorative effects of caloric restriction, selective nutrients including ω3 PUFAs, selenium, vitamins, and metabolites of vitamins, and acute/chronic exercise on the dysregulation of organokines in obesity and T2D. Finally, this study dissected the underlying molecular mechanisms by which nutrition and exercise regulate the expression and secretion of organokines in specific tissues. [ABSTRACT FROM AUTHOR]

Background: Vesicoureteral junction (VUJ) obstruction after Deflux® subureteral injection for vesicoureteral reflux (VUR) is rare and minimally invasive management has not been reported. This work investigated the patients who underwent Deflux® injection for VUR and identified those with subsequent VUJ obstruction. Methods: Medical records of matched patients from October 2003 to March 2022 were reviewed, and parameters were retrospectively studied. All patients underwent Deflux® injection. The injection was performed under general anesthesia using the same manner. For patients complicated with VUJ obstruction, the symptoms, signs, management, images, renal ultrasounds, Tc-99m dimercaptosuccinic acid renal scintigraphy, histology of VUJ region, and outcomes were documented and reported. VUJ stenosis was diagnosed by performing renal ultrasound and magnetic resonance imaging. Results: Totally 407 patients (554 ureterorenal units) received Dx/HA injections for VUR. VUJ obstruction was found in three patients (four ureterorenal units). Originally, three were grade V VUR, and one was grade IV. The repeated injection was not a risk factor for VUJ obstruction. The overall incidence of VUJ obstruction post-Dx/HA injection was 0.7% by ureter. The incidences were 0%, 0.75%, and 2.25% for grade I–III, IV, and V VUR, respectively. After the initial conversion case of pneumovesicoscopic ureteral reimplantation, the procedure was performed smoothly and successfully in the two following cases. Conclusions: Pneumovesicoscopic ureteral reimplantation offers an alternative for VUJ obstruction following Dx/HA injection for VUR. Fibrosis and foreign-body reaction may influence the feasibility. High-grade VUR and young age of injection were related to VUJ obstruction. [ABSTRACT FROM AUTHOR]

Rab proteins are small GTPases that regulate a myriad of intracellular membrane trafficking events. Rab29 is one of the Rab proteins phosphorylated by leucine-rich repeat kinase 2 (LRRK2), a Parkinson's disease-associated kinase. Recent studies suggest that Rab29 regulates LRRK2, whereas the mechanism by which Rab29 is regulated remained unclear. Here, we report a novel phosphorylation in Rab29 that is not mediated by LRRK2 and occurs under lysosomal overload stress. Mass spectrometry analysis identified the phosphorylation site of Rab29 as Ser185, and cellular expression studies of phosphomimetic mutants of Rab29 at Ser185 unveiled the involvement of this phosphorylation in counteracting lysosomal enlargement. PKCα and PKCδ were deemed to be involved in this phosphorylation and control the lysosomal localization of Rab29 in concert with LRRK2. These results implicate PKCs in the lysosomal stress response pathway comprised of Rab29 and LRRK2, and further underscore the importance of this pathway in the mechanisms underlying lysosomal homeostasis. [ABSTRACT FROM AUTHOR]

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Introduction: Conservative management of primary obstructive megaureter (POM) appears as the best option in patients with adequate ureteral drainage. Nevertheless, surgical intervention is indicated in cases of recurrent urinary tract Infections (UTIs), deterioration of split renal function, and significant obstruction. The gold standard includes: Ureteral reimplantation with or without tapering by open approach. Our objective is to report our results in the treatment of POM by Laparoscopic-Assisted Extracorporeal Ureteral Tapering Repair (EUTR) and Laparoscopic Ureteral Extravesical Reimplantation (LUER) and to evaluate the efficacy and security of this procedure. Materials and Methods: From January 2011 to January 2018 a retrospective study was carried out by reviewing the clinical records of 26 patients diagnosed with POM. All patients underwent laparoscopic ureteral reimplantation following Lich Gregoir technique. In cases of ureteral tapering, an EUTR was performed with Hendren technique. Results: In all patients LUER and EUTR were performed without conversion. No ureteral tapering was necessary in six patients. There were no intraoperative complications. At 3 months in postoperative, 1 patient presented a febrile UTI, and subsequently, a vesicoureteral reflux (VUR) grade III was diagnosed by voiding cystourethrogram. In this case, a redo laparoscopic surgery was performed. After long-term follow-up, all patients were asymptomatic without recurrence of POM or VUR. Conclusion: Laparoscopic-assisted EUTR and LUER following Lich Gregoir technique for POM constitutes a safe and effective option, with a success rate similar to that of open procedure. Nevertheless, larger randomized prospective trials and long-term follow-up are required to validate this technique. [ABSTRACT FROM AUTHOR]