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The feasibility of obtaining resistant starch type III (RS3) from malanga flour (Xanthosoma sagittifolium), as an unconventional source of starch, was evaluated using the hydrothermal treatment of autoclaving. The physicochemical characterization of RS3 made from malanga flour was carried out through the evaluation of the chemical composition, color attributes, and thermal properties. In addition, the contents of the total starch, available starch, resistant starch, and retrograded resistant starch were determined by in vitro enzymatic tests. A commercial corn starch sample was used to produce RS3 and utilized to compare all of the analyses. The results showed that native malanga flour behaved differently in most of the evaluations performed, compared to the commercial corn starch. These results could be explained by the presence of minor components that could interfere with the physicochemical and functional properties of the flour; however, the RS3 samples obtained from malanga flour and corn starch were similar in their thermal and morphological features, which may be related to their similarities in the content and molecular weight of amylose, in both of the samples. Furthermore, the yields for obtaining the autoclaved powders from corn starch and malanga flour were similar (≈89%), which showed that the malanga flour is an attractive raw material for obtaining RS3 with adequate yields, to be considered in the subsequent research.

Leptospira is a widespread zoonosis that has been linked to transmission between dogs and humans. The main purposes were to determine the seroprevalence of anti-Leptospira serum antibody and to identify the most common serovars in dogs in Spain. This is a cross-sectional study with 1,310 records of canine Leptospira testing data from Spain since 2015 to 2017. Inclusion criteria were individual cases with MAT test results for 8 serovars (Bratislava, Icterohaemorrhagiae, Australis, Pomona, Grippotyphosa, Autumnalis, Canicola and Saxkoebing) and to have the zip code data. Three hundred and thirty-eight samples (25.8%; 95%CI 23.6–28.4) were seropositive (≥1:100). According to geographic areas, North had the highest seroprevalence (38.0%; 95%CI 28.9–47.1) followed by South (29.4%; 95%CI 20.1–38.8), Center (28.6%; 95%CI 24.3–33.0), Mediterranean (22.3%; 95%CI 19.1–25.6) and Northwest (22.2%; 95%CI 7.9–36.4). Seropositivity (MAT ≥1:100) was most common to serovars Icterohaemorrhagiae (19.4%; 95%CI 17.2–21.5) and Bratislava (8.5%; 95%CI 7.0–10.0), followed by Grippotyphosa (7.2%; 95%CI 5.8–8.6), Australis (6.4%; 95%CI 5.0–7.7), Autumnalis (5.0%; 95%CI 3.8–6.2), Pomona (4.5%; 95%CI 3.3–5.6), Canicola (3.4%; 95%CI 2.4–4.4) and Saxkoebing (0.8%; 95%CI 0.3–1.3). An association was found between positivity (MAT ≥1:100) and males (P = 0.003) and dogs that were 6 years old or older were at higher risk of exposure (P = 0.001; OR 4.61; 95%CI 1.86–11.43). This study has shown that dogs in Spain are commonly exposed to Leptospira infection and points out the necessity to control the prevalence of this severe widespread zoonosis in dogs and humans.

This paper describes the development of an application for mobile devices under the iOS platform which has the objective of monitoring patients with alterations or affections from cardiac pathologies. The software tool developed for mobile devices provides a patient and a specialist doctor the ability to handle and treat disease remotely while monitoring through the technique of non-contact photoplethysmography (PPG). The mobile application works by processing red, green, and blue (RGB) color video images on a specific region of the face, thus obtaining the intensity of the pixels in the green channel. The results are then processed using mathematical algorithms and Fourier transform, moving from the time domain to the frequency domain to ensure proper interpretation and to obtain the pulses per minute (PPM). The results are favorable because a comparison of the results was made with respect to the application of a medical-grade pulse-oximeter, where an error rate of 3% was obtained, indicating the acceptable performance of our application. The present technological development provides an application tool with significant potential in the area of health.

Manual measurements of foot anthropometry can lead to errors since this task involves the experience of the specialist who performs them, resulting in different subjective measures from the same footprint. Moreover, some of the diagnoses that are given to classify a footprint deformity are based on a qualitative interpretation by the physician; there is no quantitative interpretation of the footprint. The importance of providing a correct and accurate diagnosis lies in the need to ensure that an appropriate treatment is provided for the improvement of the patient without risking his or her health. Therefore, this article presents a smart sensor that integrates the capture of the footprint, a low computational-cost analysis of the image and the interpretation of the results through a quantitative evaluation. The smart sensor implemented required the use of a camera (Logitech C920) connected to a Raspberry Pi 3, where a graphical interface was made for the capture and processing of the image, and it was adapted to a podoscope conventionally used by specialists such as orthopedist, physiotherapists and podiatrists. The footprint diagnosis smart sensor (FPDSS) has proven to be robust to different types of deformity, precise, sensitive and correlated in 0.99 with the measurements from the digitalized image of the ink mat.

The objective of this work was to investigate the effect of zein and film formulation on mechanical and structural properties of native (FNS), and oxidized with 2.5% (FOSA) and 3.5% (FOSB) banana starch. The oxidized starch showed differences from native starch due to the oxidation process, showing a decrease in lipids, proteins, and amylose. The increase of the sodium hypochlorite increased the content of carbonyl and carboxyl groups in the ranges 0.015–0.028% and 0.022–0.031%, respectively. The film obtained from FOSB displayed the highest tensile strength (5.05 MPa) and satisfactory elongation value (27.1%). The zein addition caused a decrease in these mechanical properties, as well as a significant decrease in water vapour permeability (WVP). However, films from FOSA and FOSB showed higher permeability than that of the native starch. The addition of glycerol and the level of oxidation increased the films moisture. Micrographs showed that, during the oxidation process, impurities were largely eliminated from the starch granule, noting more homogeneous structures both in granules and films.

The risk of progression from Mycobacterium tuberculosis (M.tb) infection to active tuberculosis (TB) disease varies markedly with age. TB disease is significantly less likely in pre-adolescent children above 4 years of age than in very young children or post-pubescent adolescents and young adults. We hypothesized that pro-inflammatory responses to M.tb in pre-adolescent children are either less pronounced or more regulated, than in young adults. Inflammatory and antimicrobial mediators, measured by microfluidic RT-qPCR and protein bead arrays, or by analyzing published microarray data from TB patients and controls, were compared in pre-adolescent children and adults. Multivariate analysis revealed that M.tb-uninfected 8-year-old children had lower levels of myeloid-associated pro-inflammatory mediators than uninfected 18-year-old young adults. Relative to uninfected children, those with M.tb-infection had higher levels of similar myeloid inflammatory responses. These inflammatory mediators were also expressed after in vitro stimulation of whole blood from uninfected children with live M.tb. Our findings suggest that myeloid inflammation is intrinsically lower in pre-pubescent children than in young adults. The lower or more regulated pro-inflammatory responses may play a role in the lower risk of TB disease in this age group.

Eradication of tuberculosis (TB), the world's leading cause of death due to infectious disease, requires a highly efficacious TB vaccine. Many TB vaccine candidates are in pre-clinical and clinical development but only a few can be advanced to large-scale efficacy trials due to limited global resources. We aimed to perform a statistically rigorous comparison of the antigen-specific T cell responses induced by six novel TB vaccine candidates and the only licensed TB vaccine, Bacillus Calmette-Guérin (BCG). We propose that the antigen-specific immune response induced by such vaccines provides an objective, data-driven basis for prioritisation of vaccine candidates for efficacy testing. We analyzed frequencies of antigen-specific CD4 and CD8 T cells expressing IFNγ, IL-2, TNF and/or IL-17 from adolescents or adults, with or without Mycobacterium tuberculosis (M.tb) infection, who received MVA85A, AERAS-402, H1:IC31, H56:IC31, M72/AS01E, ID93+GLA-SE or BCG. Two key response characteristics were analyzed, namely response magnitude and cytokine co-expression profile of the memory T cell response that persisted above the pre-vaccination response to the final study visit in each trial. All vaccines preferentially induced antigen-specific CD4 T cell responses expressing Th1 cytokines; levels of IL-17-expressing cells were low or not detected. In M.tb-uninfected and -infected individuals, M72/AS01E induced higher memory Th1 cytokine-expressing CD4 T cell responses than other novel vaccine candidates. Cytokine co-expression profiles of memory CD4 T cells induced by different novel vaccine candidates were alike. Our study suggests that the T cell response feature which most differentiated between the TB vaccine candidates was response magnitude, whilst functional profiles suggested a lack of response diversity. Since M72/AS01E induced the highest memory CD4 T cell response it demonstrated the best vaccine take. In the absence of immunological correlates of protection, the likelihood of finding a protective vaccine by empirical testing of candidates may be increased by the addition of candidates that induce distinct immune characteristics.

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).)

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.

Objective: To describe the incidence, predisposing factors and management of postoperative vesicoureteral reflux (VUR) after high-pressure balloon dilation to treat primary obstructive megaureter (POM)., Materials and Methods: We have reviewed patients that underwent endoscopic treatment for POM from May 2008 to November 2013. All patients were evaluated with renal ultrasound, voiding cystourethrography and diuretic renogram. Endoscopic treatment was done with high-pressure balloon dilation of the ureterovesical junction under general anesthesia; a double-J stenting was done in all patients. Follow-up was performed with ultrasonography, voiding cystourethrography and a diuretic renogram in all patients., Results: Fifteen boys and five girls with a mean age of 14.18 months (3-103) were reviewed. A total of 22 ureters underwent HPBD to treat POM. Ureterohydronephrosis improves in 19 ureters. After endoscopic treatment, six ureters developed VUR. Four ureters were managed surgically, and in the other two, VUR disappeared in a second cystogram. The presence of parameatal diverticulum in the preoperative cystography and those patients with bilateral POM are factors related to postoperative VUR (p < 0.05). Urinary tract infection after HPBD was observed in four patients, but only one of them was affected with VUR.

Objective: To report the results of fetal cystoscopic laser ablation of posterior urethral valves (PUV) in a consecutive series in two referral centers., Methods: Twenty pregnant women with a presumptive isolated PUV were treated with fetal cystoscopy under local anesthesia. Identification and fulguration of the PUV by one or several firing-contacts with diode laser were attempted. Perinatal and long-term outcomes were prospectively recorded., Results: The median gestational age at procedure was 18.1 weeks (range 15.0-25.6), and median operation time was 24 min (range 15-40). Access to the urethra was achieved in 19/20 (95%) cases, and postoperative, normalization of bladder size and amniotic fluid was observed in 16/20 (80%). Overall, there were 9 (45%) terminations of pregnancy and 11 women (55%) delivered a liveborn baby at a mean gestational age of 37.3 (29.1-40.2) weeks. No infants developed pulmonary hypoplasia and all were alive at 15-110 months. Eight (40% of all fetuses, 72.7% of newborns) had normal renal function and 3 (27.3%) had renal failure awaiting renal transplantation., Conclusion: Fetoscopic laser ablation for PUV can achieve bladder decompression and amniotic fluid normalization with a single procedure in selected cases with anyhydramnios. There is still a significant risk of progression to renal failure pre or postnatally., (© 2014 S. Karger AG, Basel.)

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.

Purpose: To compare efficacy of Cohen's ureteral reimplantation and endoscopic treatment with Dx/HA in patients with primary VUR grades II, III and IV., Methods: From April 2002 to June 2004, patients over 1 year old with VUR grade I, II, III or IV were included. Patients were randomized into two groups: endoscopic treatment (ET) or ureteral reimplantation (UR). In the ET group, an ultrasonography study was performed 24 h and 1 month after surgery, and two voiding cystourethrographies at 3 and 6 months post treatment. In the UR group, an ultrasonography study was done 7 days and 1 month after surgery and a micturial cystography 6 months post surgery. A postoperative nuclear direct cystogram was performed 5 years later in both groups., Results: A total of 41 patients were included in this study: in ET 22 patients with 35 refluxing ureters and in UR 19 patients with 32 refluxing ureters. The VUR grades in ET were: 16 grade II, 16 grade III and 3 grade IV; and in UR: 15 grade II, 12 grade III and 5 grade IV. VUR was resolved in 91% (32/35) of ET (28% of ureters needed a second injection), and in 100% of UR group. Five years after the procedure, VUR was still resolved in 30/32 of ET and 32/32 of UR., Conclusion: Short- and long-term follow up shows that multiple endoscopic treatment of VUR grades II, III and IV with Dx/HA is as effective as ureteral reimplantation., (Copyright © 2013 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Objective: To present our cases of ureteral obstruction after endoscopic treatment of vesicoureteral reflux (VUR) with dextranomer/hyaluronic acid (Dx/HA)., Patients and Methods: We collected data from patients who had suffered ureteral obstruction after endoscopic treatment of VUR with Dx/HA in our institution., Results: From April 2002 to April 2011 we treated endoscopically 475 ureters with VUR, and detected 5 ureteral obstructions. Median age at reflux treatment was 39 months. Reflux grade before treatment was III in one patient and IV in four. Three ureterovesical junctions (UVJ) were blocked after a second endoscopic treatment. The median of Dx/HA injected was 1 ml (0.6-1.1). In two patients ureteral obstruction presented acutely and was treated with a ureteral stent. In the other three, the ureteral obstruction appeared gradually and was detected by ultrasound scans and MAG3 diuretic renogram; one underwent nephrectomy because of poor renal function, and the other two were treated with endoscopic dilatation of the UVJ. In all these patients both reflux and obstructions have resolved., Conclusions: On preoperative cystography, three of the patients had a narrowed distal ureter, and probably had a refluxing and obstructive megaureter. Other causes are not clear, except for those patients with acute presentation in whom edema of the UVJ was found. Ureteral obstruction after endoscopic treatment of VUR is rare. Endoscopic intervention such as ureteral stent placement or high-pressure balloon dilatation of the UVJ has good results as a treatment of acute and delayed obstruction., (Copyright © 2013 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Purpose: We describe the efficacy of dilation of the ureterovesical junction to treat primary obstructive megaureter., Materials and Methods: A total of 13 patients with primary obstructive megaureter were treated from May 2008 to December 2010. Of these patients 8 were diagnosed prenatally and the others were diagnosed after a urinary tract infection. Preoperative studies included ultrasonography, voiding cystourethrography despite vesicoureteral reflux and diuretic isotopic renogram (mercaptoacetyltriglycine). With the patient under general anesthesia, high pressure balloon dilation of the ureterovesical junction was performed under direct and fluoroscopic vision until the disappearance of the narrowed ring. A Double-J(®) catheter was positioned, and 2 months later it was withdrawn and the ureterovesical junction was reviewed. A secondary treatment was performed in those in whom the ureterovesical junction was still narrow. Followup was performed with ultrasonography, cystourethrography and isotopic diuretic renography., Results: A total of 18 procedures were performed in 13 patients (median age 7 months, range 4 to 24). Median diameter of the distal ureter was 14 mm (range 10 to 26), and median diameter of the renal pelvis and calyx was 27 mm (range 10 to 47) and 12 mm (range 9 to 26), respectively. Significant postoperative improvement of hydroureteronephrosis was observed in 11 of 13 patients and vesicoureteral reflux was found in 2. Only 3 patients needed ureteral reimplantation after endoscopic treatment due to hydroureteronephrosis in 2 and high grade vesicoureteral reflux in 1., Conclusions: High pressure balloon dilation of the ureterovesical junction is effective in treating primary obstructive megaureter, but long-term followup is needed., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To analyze the initial experience in our first patients with ureteropelvic junction obstruction (UPJO) treated by laparoscopic surgery., Patients and Methods: All laparoscopic Anderson-Hynes pyeloplasties performed from July 2007 to April 2009 were analyzed. Before surgery, patients underwent a renal ultrasound and isotope renogram. A double J catheter was left in place and subsequently removed. Patients were followed up by ultrasound and renography., Results: Fourteen patients with a median age of 8.6 years were analyzed. Preoperative ultrasound showed a median renal pelvis diameter of 34.5 mm. Median operating time was 235 min, and median hospital stay 5.5 days. Median renal pelvis diameter decreased in all patients (13.5 mm)., Conclusions: Laparoscopy is an effective procedure for UPJO correction in children, although operating times are still long.

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.)

Natural IgM are involved in numerous immunological functions but the genetic factors that control the homeostasis of its secretion and upholding remain unknown. Prompted by the finding that C57BL/6 mice had significantly lower serum levels of IgM when compared with BALB/c mice, we performed a genome-wide screen and found that the level of serum IgM was controlled by a QTL on chromosome 13 reaching the highest level of association at marker D13Mit266 (LOD score=3.54). This locus was named IgMSC1 and covered a region encompassing the interferon-regulatory factor 4 gene (Irf4). The number of splenic mature B cells in C57BL/6 did not differ from BALB/c mice but we found that low serum levels of IgM in C57BL/6 mice correlated with lower frequency of IgM-secreting cells in the spleen and in the peritoneal cavity. These results suggested that C57BL/6 mice have lower efficiency in late B-cell maturation, a process that is highly impaired in Irf4 knockout mice. In fact, we also found reduced Irf4 gene expression in B cells of C57BL/6 mice. Thus, we propose Irf4 as a candidate for the IgMSC1 locus, which controls IgM homeostatic levels at the level of B-cell terminal differentiation.

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.

Objectives: To analyze the urinary repercussions in patients with lipomyelomeningocele., Methods: From 1976 to 1993, 20 patients (11 males and 9 females), aged 12-17 years had been referred to our department. All patients were evaluated clinically and analytically, urodynamically and by imaging techniques (cystography, US or IVP)., Results: Neurogenic bladder dysfunction was observed in 13 patients (65%); 4 of these patients had vesicoureteric reflux and 2 had residual pyelonephritic lesions. These 13 patients with neurogenic bladder were incontinent: 4 were on intermittent bladder catheterization, 2 patient were receiving oxybutinine, 3 were on intermittent catheterization+oxybutinine, and one patient has an artificial sphincter. Four male patients under 7 years will be starting intermittent catheterization. Of the patients with vesicoureteric reflux, 3 were treated with medication and one was submitted to surgery., Conclusions: Urinary tract involvement is not uncommon in these patients. However, it is not inevitable and the degree of severity is variable. Early diagnosis of neurogenic bladder dysfunction is fundamental for management.

All the patients who underwent implantation of an artificial urinary sphincter can have three types of complications: those coming from the own patient, mechanical complications and other aleatory ones. J. L. C. A., a 13-year-old boy with secondary neurogenic bladder, received the implantation of a model AUS 800 artificial urinary sphincter for urinary incontinence. After 15 months without problems, he was admitted in our hospital with pump erosion in the scrotum. He was operated on and the pump system was preserved. No plain roentgenograms were made neither before nor after surgical procedure. However, the balloon pressure reservoir was not seen in a control pielogram performed before his discharge from the hospital. Three months later the entire device should be removed because of infection. In the operation a cut off tube was found. A new artificial urinary sphincter was reimplanted and the cuff was placed around the bulbous urethra one year later. Retrospective analysis of this case can help to review the possible complications and their management.