Impact of chemotherapy on surgical outcomes in ileostomy reversal: a propensity score matching study from a single centre.

PURPOSE: In patients with chemotherapy, there is no consensus on the timing of ileostomy closure. Ileostomy reversal could improve the quality of life and minimise the long-term adverse events of delayed closure. In this study, we evaluated the impact of chemotherapy on ileostomy closure and searched for the predictive factors for complications. METHODS: We retrospectively analysed 212 patients with rectal cancer who underwent ileostomy closure surgery during and without chemotherapy and were consecutively enrolled between 2010 and 2016. As a result of the heterogeneity of the two groups, propensity score matching (PSM) was performed with a 1:1 PSM cohort. RESULTS: A total of 162 patients were included in the analysis. The overall stoma closure-related complications (12.4% vs. 11.1%, p = 1.00) and major complications (2.5% vs. 6.2%, p = 0.44) were not significantly different between the two groups. Multivariate analysis demonstrated that chronic kidney disease and bevacizumab use are risk factors for major complications. CONCLUSION: Patients with oral or intravenous chemotherapy can safely have ileostomy closure with an adequate time delay from chemotherapy. When patients use bevacizumab, major complications related to ileostomy closure should still be cautioned.

Evaluation of walking activity data during pregnancy as an indicator of pregnancy loss in dairy cattle.

A pregnancy loss or abortion can be assumed when a dairy cow that has been previously diagnosed pregnant shows signs of estrus. In herds using leg-based pedometers as a tool to detect cows in estrus, a sudden increase in walking activity (hereafter, activity peaks) relative to a certain threshold activity triggers an estrous alert that can be confused with a pregnancy loss. The objective of this study was to determine whether pregnant cows can show activity peaks as measured by pedometers. We used data from a dairy herd of 250 milking cows using pedometers as a means of measuring walking activity to detect cows in estrus. Two databases were used in this study, which included the walking activity of the entire herd recorded by the pedometers from January 1, 2018, to December 31, 2021 (database 1), and the calving dates, the insemination dates, the dates when a pregnancy diagnosis was declared pregnant, the dates when a pregnancy diagnosis was declared not pregnant or open, and the abortion dates (database 2). Activity peaks were identified within an experimental unit, which was defined as pregnant cows showing an insemination event followed by a confirmed pregnancy and subsequent calving. The activity peaks were identified using the peak searching algorithm that compares the step count on a given day with the step counts of its adjacent days. The candidate peaks were characterized for their magnitudes by the prominence metric. A chi-squared test was performed to test the specificity of the system. From the 4-yr database, 537 pregnancies or experimental units were identified, and 77 pregnancies showed 1 or more peaks, which means that 14.4% of the pregnancies showed activity peaks. Within the pregnancies showing peaks (n = 77), the median equaled 1 peak/pregnancy, the average equaled 1.53 peaks/pregnancy, and the maximum equaled 13 peaks/pregnancy. In conclusion, activity peaks can be observed for pregnant cows using pedometers. These peaks could generate false estrous alerts during the pregnancy period when using pedometers, and these false alerts should not be interpreted as pregnancy losses.

Integrated proteome and lipidome analysis of naturally aged safflower seeds varying in vitality.

Seed ageing has an important effect on germination and productivity. During natural ageing, seed vigour decreases rapidly but, to date, the molecular mechanisms underlying this decrease have not been fully elucidated. Using omics, some of the details regarding seed vigour decline during natural ageing might be elucidated through integrated analysis. Safflower seed germination and physio-biochemical changes during natural ageing (stored for 4, 16 and 28 months) were determined. Proteome and lipidome profiling during natural seed ageing was performed, and the differentially expressed proteins and lipid metabolite species analysed. The surface and internal structures of cotyledons were observed. An integrating analysis of the proteome and lipidome was also carried out. Natural seed ageing significantly decreased safflower seed germination and vigour. 4,184 proteins and 1,193 lipids were quantified, both of which show huge differences among the different naturally aged seeds. The surface of the cotyledons collapsed and cracked, and the oil bodies become looser during natural ageing. The total content of DAG and PA increased, while the content of TAG and PL (PC, PE, PS, PI and PL) significantly decreased during seeds ageing. Two lipase genes (HH-026818-RA and HH-025320) likely participated in this degradation of lipids. We conclude that the enzymes that participate in glycerolipid metabolism and fatty acid degradation probably lead to the degradation of oil bodies (TAG) and membrane lipids (PC, PE, PS, PI, PG) and, ultimately, destroy the structure, causing a decline in seed vigour during natural seed ageing.

Re-focusing on Agnathia-Otocephaly complex.

OBJECTIVES: Agnathia-otocephaly complex is a rare condition characterized by mandibular hypoplasia or agnathia, ear anomalies (melotia/synotia) and microstomia with aglossia. This severe anomaly of the first branchial arch is most often lethal. The estimated incidence is less than 1 in 70.000 births, with etiologies linked to both genetic and teratogenic factors. Most of the cases are sporadic. To date, two genes have been described in humans to be involved in this condition: OTX2 and PRRX1. Nevertheless, the overall proportion of mutated cases is unknown and a significant number of patients remain without molecular diagnosis. Thus, the involvement of other genes than OTX2 and PRRX1 in the agnathia-otocephaly complex is not unlikely. Heterozygous mutations in Cnbp in mice are responsible for mandibular and eye defects mimicking the agnathia-otocephaly complex in humans and appear as a good candidate. Therefore, in this study, we aimed (i) to collect patients presenting with agnathia-otocephaly complex for screening CNBP, in parallel with OTX2 and PRRX1, to check its possible implication in the human phenotype and (ii) to compare our results with the literature data to estimate the proportion of mutated cases after genetic testing. MATERIALS AND METHODS: In this work, we describe 10 patients suffering from the agnathia-otocephaly complex. All of them benefited from array-CGH and Sanger sequencing of OTX2, PRRX1 and CNBP. A complete review of the literature was made using the Pubmed database to collect all the patients described with a phenotype of agnathia-otocephaly complex during the 20 last years (1998-2019) in order (i) to study etiology (genetic causes, iatrogenic causes…) and (ii), when genetic testing was performed, to study which genes were tested and by which type of technologies. RESULTS: In our 10 patients' cohort, no point mutation in the three tested genes was detected by Sanger sequencing, while array-CGH has allowed identifying a 107-kb deletion encompassing OTX2 responsible for the agnathia-otocephaly complex phenotype in 1 of them. In 4 of the 70 cases described in the literature, a toxic cause was identified and 22 out the 66 remaining cases benefited from genetic testing. Among those 22 patients, 6 were carrying mutation or deletion in the OTX2 gene and 4 in the PRRX1 gene. Thus, when compiling results from our cohort and the literature, a total of 32 patients benefited from genetic testing, with only 34% (11/32) of patients having a mutation in one of the two known genes, OTX2 or PRRX1. CONCLUSIONS: From our work and the literature review, only mutations in OTX2 and PRRX1 have been found to date in patients, explaining around one third of the etiologies after genetic testing. Thus, agnathia-otocephaly complex remains unexplained in the majority of the patients, which indicates that other factors might be involved. Although involved in first branchial arch defects, no mutation in the CNBP gene was found in this study. This suggests that mutations in CNBP might not be involved in such phenotype in humans or that, unlike in mice, a compensatory effect might exist in humans. Nevertheless, given that agnathia-otocephaly complex is a rare phenotype, more patients have to be screened for CNBP mutations before we definitively conclude about its potential implication. Therefore, this work presents the current state of knowledge on agnathia-otocephaly complex and underlines the need to expand further the understanding of the genetic bases of this disorder, which remains largely unknown. CLINICAL RELEVANCE: We made here an update and focus on the clinical and genetic aspects of agnathia-otocephaly complex as well as a more general review of craniofacial development.

Modifiable factors related to 7-year renal outcomes in subjects with type 2 diabetes and chronic kidney disease stage 3.

BACKGROUND AND AIMS: Subjects with diabetes are prone to a rapid decline in renal function and major adverse cardiovascular events when they reach chronic kidney disease (CKD) stage 3. This study aimed to identify modifiable risk factors associated with the progression of CKD in this population. SETTINGS AND DESIGN: An observational cohort study. METHODS AND MATERIALS: A total of 320 type 2 diabetic patients with CKD stage 3 registered in the shared-care-system in our hospital in 2010 were regularly followed up for 7 years. Demographic, laboratory, medication, and fundus examination data of these subjects were collected and analyzed. STATISTICAL ANALYSIS USED: Cox regression was used to identify factors associated with changes in CKD stage. RESULTS: During the 7-year follow-up period, 204 cases (63.7%) remained at CKD stage 3 while 79 cases (24.7%) progressed to stage 4 or 5 and 37 cases (11.6%) improved to stage 1 or 2. The change in estimated glomerular filtration rate (eGFR) in the first 2 years and variations in glycated hemoglobin (HbA1c) over 7 years were independent factors of both progression (hazard ratio (HR) 1.098 and 1.710, respectively) and improvement (HR 0.919 and 0.231, respectively) of CKD stage. Variations in systolic blood pressure (SBP) was also found as an independent factor for progression of renal function (HR 1.052). CONCLUSIONS: Our results demonstrated that fluctuations in HbA1c and SBP, and changes in eGFR during the first 2 years of treatment were associated with the long-term renal outcomes in type 2 diabetic patients with CKD stage 3.

YAP/TAZ Regulate Elevation and Bone Formation of the Mouse Secondary Palate.

Clefting of the secondary palate is one of the most common congenital anomalies, and the multiple corrective surgeries that individuals with isolated cleft palate undergo are associated with major costs and morbidities. Secondary palate development is a complex, multistep process that includes the elevation of the palatal shelves from a vertical to horizontal position, a process that is not well understood. The Hippo signaling cascade is a mechanosensory pathway that regulates morphogenesis, homeostasis, and regeneration by controlling cell proliferation, apoptosis, and differentiation, primarily via negative regulation of the downstream effectors, Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ). We deleted Yap/Taz throughout the palatal shelf mesenchyme as well as specifically in the posterior palatal shelf mesenchyme, using the Osr2Cre and Col2Cre drivers, respectively, which resulted in palatal shelf elevation delay and clefting of the secondary palate. In addition, the deletion resulted in undersized bones of the secondary palate. We next determined downstream targets of YAP/TAZ in the posterior palatal shelves, which included Ibsp and Phex, genes involved in mineralization, and Loxl4, which encodes a lysyl oxidase that catalyzes collagen crosslinking. Ibsp, Phex, and Loxl4 were expressed at decreased levels in the ossification region in the posterior palatal shelf mesenchyme upon deletion of Yap/Taz. Furthermore, collagen levels were decreased specifically in the same region prior to elevation. Thus, our data suggest that YAP/TAZ may regulate collagen crosslinking in the palatal shelf mesenchyme, thus controlling palatal shelf elevation, as well as mineralization of the bones of the secondary palate.

First trimester placental vascular indices and volume by three-dimensional ultrasound in pre-gravid overweight women.

OBJECTIVES: To investigate changes of placental vascular indices and volume in pre-gravid overweight Chinese women during the first trimester using three-dimensional power Doppler ultrasound. METHODS: This was a prospective observational study of the morphology of placentas in pre-gravid overweight (body mass index (BMI) ≥ 24 kg/m2) and non-overweight (BMI < 24 kg/m2) Chinese women during the first trimester of pregnancy. Data on placental vascular indices (vascularization index, flow index, and vascularization flow index (VFI)), placental volume, uterine artery pulsatility index (PI), and neonatal outcomes were obtained during the first trimester and analyzed. Linear regression analysis was used to evaluate confounding factors between BMI and ultrasound indices. RESULTS: Of the 429 pregnant women enrolled, 68 (15.9%) were pre-gravid overweight. Placental VFI was significantly lower in the overweight group (p = 0.037). Conversely, placental volume was significantly larger in the overweight group (p = 0.044), and uterine artery PI was significantly higher in the overweight group (p = 0.021). After adjustments for confounding factors, there were still significant differences in placental VFI (unstandardized coefficient (B) -0.666, 95% confidence interval (CI) -1.306 - (-0.025)), placental volume (B 2.458, 95% CI 0.071-4.844), and uterine artery PI (B 0.152, 95% CI 0.030-0.274) between the two groups. CONCLUSIONS: Placental vascular indices using three-dimensional power Doppler ultrasound can provide an insight into placental vascularization in pre-gravid overweight women in early pregnancy. Alterations in placental VFI, placental volume, and uterine artery PI occur during the first trimester in pre-gravid overweight women.

Evaluating Ga-68 Peptide Conjugates for Targeting VPAC Receptors: Stability and Pharmacokinetics.

PURPOSE: In recent years, considerable progress has been made in the use of gallium-68 labeled receptor-specific peptides for imaging oncologic diseases. The objective was to examine the stability and pharmacokinetics of [68Ga]NODAGA and DOTA-peptide conjugate targeting VPAC [combined for vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP)] receptors on tumor cells. PROCEDURES: A VPAC receptor-specific peptide was chosen as a model peptide and conjugated to NODAGA and DOTA via solid-phase synthesis. The conjugates were characterized by HPLC and MALDI-TOF. Following Ga-68 chelation, the radiochemical purity of Ga-68 labeled peptide conjugate was determined by radio-HPLC. The stability was tested against transmetallation using 100 nM Fe3+/Zn2+/Ca2+ ionic solution and against transchelation using 200 µM DTPA solution. The ex vivo and in vivo stability of the Ga-68 labeled peptide conjugate was tested in mouse plasma and urine. Receptor specificity was determined ex vivo by cell binding assays using human breast cancer BT474 cells. Positron emission tomography (PET)/X-ray computed tomography (CT) imaging, tissue distribution, and blocking studies were performed in mice bearing BT474 xenografts. RESULTS: The chemical and radiochemical purity was greater than 95 % and both conjugates were stable against transchelation and transmetallation. Ex vivo stability at 60 min showed that the NODAGA-peptide-bound Ga-68 reduced to 42.1 ± 3.7 % (in plasma) and 37.4 ± 2.9 % (in urine), whereas the DOTA-peptide-bound Ga-68 was reduced to 1.2 ± 0.3 % (in plasma) and 4.2 ± 0.4 % (in urine) at 60 min. Similarly, the in vivo stability for [68Ga]NODAGA-peptide was decreased to 2.1 ± 0.2 % (in plasma) and 2.2 ± 0.4 % (in urine). For [68Ga]DOTA-peptide, it was decreased to 1.4 ± 0.3 % (in plasma) and 1.2 ± 0.4 % (in urine) at 60 min. The specific BT474 cell binding was 53.9 ± 0.8 % for [68Ga]NODAGA-peptide, 25.8 ± 1.4 % for [68Ga]-DOTA-peptide, and 18.8 ± 2.5 % for [68Ga]GaCl3 at 60 min. Inveon microPET/CT imaging at 1 h post-injection showed significantly (p < 0.05) higher tumor to muscle (T/M) ratio for [68Ga]NODAGA-peptide (3.4 ± 0.3) as compared to [68Ga]DOTA-peptide (1.8 ± 0.6). For [68Ga]GaCl3 and blocked mice, their ratios were 1.5 ± 0.6 and 1.5 ± 0.3 respectively. The tissue distributions data were similar to the PET imaging data. CONCLUSION: NODAGA is superior to DOTA in terms of radiolabeling kinetics. The method of radiolabeling was reproducible and yielded higher specific activity. Although both agents have relatively low in vivo stability, PET/CT imaging studies delineated BC tumors with [68Ga]NODAGA-peptide, but not with [68Ga]DOTA-peptide.

[Study on the mechanism of serotype conversion of historical isolates of Shigella flexneri].

Objective: The serotype screening of Shigella flexneri from 1934 to 1965 preserved by the National Center for Medical Culture Collections was carried out, and the molecular characteristics of the serotype conversion strains were studied. Methods: Serotyping of Shigella flexneri in this study was conducted by slide agglutination and multiplex PCR, respectively. The gtrⅡ gene sequence alignment and pulsed field gel electrophoresis typing were performed on the serotype conversion strains. Results: Among the 255 strains of Shigella flexneri preserved in CMCC (B) from 1934 to 1965, 79 were carrying gtrⅡ gene, of which 19 strains and 1 strain were agglutinated with the Y serotype and X serotype, respectively, and furthermore, the multiplex PCR assays results showed serotypes 2a and 2b, respectively, and the strains were considered to have serotype conversion. The 20 strains carrying the gtrⅡ gene showed multiple nucleotide mutations. Besides 3 strains of 3 amino acid mutations, the amino acid sequences of the other 17 strains showed a stop codon in advance, resulting in functional inactivation of gtrⅡ. PFGE analysis revealed that the similarity between the serotype Y strain carrying the gtrⅡ gene and the serotype 2a strain was 75.8%-100%, and the similarity between the serotype X strain carrying the gtrⅡ gene and the serotype 2b strain was 81.6%-100%. Conclusion: Mutations in the gtrⅡ gene are more complicated in serotype-transforming Shigella flexneri serotype Y or X strains. Molecular typing suggests that the serotype-transforming Shigella flexneri serotype Y or X strains may be derived from the Shigella flexneri serotype 2a or 2b, and advance the serotype conversion to 1949.

Low-expression of lncRNA FER1L4 might be a prognostic marker in osteosarcoma.

OBJECTIVE: To investigate the potential role of Long non-coding RNA (lncRNA) FER1L4 in the diagnosis and prognostic assessment of osteosarcoma. PATIENTS AND METHODS: LncRNA FER1L4 expression in osteosarcoma samples was detected by real-time PCR. The Kaplan-Meier method was used to analyze the relationship between lncRNA FER1L4 expression and the survival time of patients. RESULTS: LncRNA FER1L4 expression was decreased in osteosarcoma samples. LncRNA FER1L4 was not related to the gender and age of patients, but was significantly associated with disease stage, metastasis, and tumor differentiation. CONCLUSIONS: Low-expression of lncRNA FER1L4 might be a prognostic marker in osteosarcoma.

A dispermic chimerism detected in a Taiwanese potential unrelated hematopoietic stem cell donor.

Chimerism is defined as the presence of 2 or more than 1 genetically distinct cell populations in an organism. Dispermic chimeras are derived from the fertilization of 1 or 2 matured nuclei by 2 sperms. We here report detection of a healthy and phenotypically normal female with normal ABO red blood cell typing in whom dispermic chimerism was suspected after 3 alleles were identified at multiple human leukocyte antigen (HLA) loci using molecular HLA analysis. Molecular HLA typing showed the donor to have 3 HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1 alleles in blood, saliva and nail samples. In addition, 3 of her 9 short tandem repeat loci also showed to have 3 distinct alleles in blood, nail and saliva specimens. In all investigations, the third alleles were attributed to a dual paternal contribution. This case represents a dispermic chimerism, with 2 paternal and 1 maternal haplotypes variably distributed throughout body tissues in a healthy and phenotypically normal female without abnormalities in erythrocyte ABO blood group. The origin of this chimerism is probably due to the fertilization of a single egg and its polar body, or a parthenogenetic egg, by 2 sperms.

Detection of HLA-DRB1*04:207, a novel HLA-DRB1*04 variant, in a Taiwanese hematopoietic stem cell donor.

Recombination may result in the formation of HLA-DRB1*04:207.

The Global Landscape of Occupational Exposure Limits--Implementation of Harmonization Principles to Guide Limit Selection.

Occupational exposure limits (OELs) serve as health-based benchmarks against which measured or estimated workplace exposures can be compared. In the years since the introduction of OELs to public health practice, both developed and developing countries have established processes for deriving, setting, and using OELs to protect workers exposed to hazardous chemicals. These processes vary widely, however, and have thus resulted in a confusing international landscape for identifying and applying such limits in workplaces. The occupational hygienist will encounter significant overlap in coverage among organizations for many chemicals, while other important chemicals have OELs developed by few, if any, organizations. Where multiple organizations have published an OEL, the derived value often varies considerably-reflecting differences in both risk policy and risk assessment methodology as well as access to available pertinent data. This article explores the underlying reasons for variability in OELs, and recommends the harmonization of risk-based methods used by OEL-deriving organizations. A framework is also proposed for the identification and systematic evaluation of OEL resources, which occupational hygienists can use to support risk characterization and risk management decisions in situations where multiple potentially relevant OELs exist.

Chinese herbal medicine for miscarriage affects decidual micro-environment and fetal growth.

INTRODUCTION: Intrauterine growth restriction complicates 5-10% of pregnancies. This study aims to test the hypothesis that Chinese herbal formula, JLFC01, affects pregnancy and fetal development by modulating the pro-inflammatory decidual micro-environment. METHODS: Human decidua from gestational age-matched elective terminations or incomplete/missed abortion was immunostained using anti-CD68 + anti-CD86 or anti-CD163 antibodies. qRT-PCR and Luminex assay measured the effects of JLFC01 on IL-1ß- or TNF-α-induced cytokine expression in first trimester decidual cells and on an established spontaneous abortion/intrauterine growth restriction (SA/IUGR)-prone mouse placentae. The effect of JLFC01 on human endometrial endothelial cell angiogenesis was evaluated by average area, length and numbers of branching points of tube formation. Food intake, litter size, fetal weight, placental weight and resorption rate were recorded in SA/IUGR-prone mouse treated with JLFC01. qRT-PCR, Western blot and immunohistochemistry assessed the expression of mouse placental IGF-I and IGF-IR. RESULTS: In spontaneous abortion, numbers of decidual macrophages expressing CD86 and CD163 are increased and decreased, respectively. JLFC01 reduces IL-1ß- or TNF-α-induced GM-CSF, M-CSF, C-C motif ligand 2 (CCL2), interferon-γ-inducible protein-10 (IP-10), CCL5 and IL-8 production in first trimester decidual cells. JLFC01 suppresses the activity of IL-1ß- or TNF-α-treated first trimester decidual cells in enhancing macrophage-inhibited angiogenesis. In SA/IUGR-prone mice, JLFC01 increases maternal food intake, litter size, fetal and placental weight, and reduces fetal resorption rate. JLFC01 induces IGF-I and IGF-IR expression and inhibits M-CSF, CCL2, CCL5, CCL11, CCL3 and G-CSF expression in the placentae. DISCUSSION: JLFC01 improves gestation by inhibiting decidual inflammation, enhancing angiogenesis and promoting fetal growth.

Nontyphoidal salmonella urinary tract infection in a case of hyperparathyroidism and nephrocalcinosis.

Nontyphoidal Salmonella infections often present with self-limited gastroenteritis. Extraintestinal focal infections are uncommon but have high mortality and morbidity. Urinary tract infection caused by nontyphoidal Salmonella is usually associated with structural abnormalities of the urinary tract. Nephrocalcinosis and nephrolithiasis are the major risk factors. Although primary hyperparathyroidism has been reported to increase the risk of nephrocalcinosis and nephrolithiasis, little is known about the association between hyperparathyroidism and Salmonella urinary tract infection. We report the case of a 37-year old man who had a history of primary hyperparathyroidism and bilateral nephrocalcinosis and who developed urinary tract infection. Salmonella Group D was isolated from his urine specimen. Salmonella should be considered as a possible causality organism in patients with primary hyperparathyroidism and nephrocalcinosis who develop urinary tract infection. These patients need to be aware of the potential risks associated with salmonellosis.

Nontyphoidal Salmonella urinary tract infection in a case of hyperparathyroidism and nephrocalcinosis / Infección de las vías urinaria por Salmonella no tifoidea en un caso de hiperparatiroidismo y nefrocalcinosis

Nontyphoidal Salmonella infections often present with self-limited gastroenteritis. Extraintestinal focal infections are uncommon but have high mortality and morbidity. Urinary tract infection caused by nontyphoidal Salmonella is usually associated with structural abnormalities of the urinary tract. Nephrocalcinosis and nephrolithiasis are the major risk factors. Although primary hyperparathyroidism has been reported to increase the risk of nephrocalcinosis and nephrolithiasis, little is known about the association between hyperparathyroidism and Salmonella urinary tract infection. We report the case of a 37-year old man who had a history of primary hyperparathyroidism and bilateral nephrocalcinosis and who developed urinary tract infection. Salmonella Group D was isolated from his urine specimen. Salmonella should be considered as a possible causality organism in patients with primary hyperparathyroidism and nephrocalcinosis who develop urinary tract infection. These patients need to be aware of the potential risks associated with salmonellosis.

Las infecciones por Salmonella no tifoidea se presentan a menudo con gastroenteritis auto-limitada. Las infecciones extra-intestinales focales son poco frecuentes, pero tienen una alta mortalidad y morbilidad. La infección de las vías urinarias causada por la Salmonella no tifoidea se asocia generalmente a anomalías estructurales de las vías urinarias. La nefrocalcinosis y la nefrolitiasis son los principales factores de riesgo. Aunque se ha reportado que el hiperparatiroidismo primario aumenta el riesgo de la nefrocalcinosis y la nefrolitiasis, poco se sabe sobre la asociación entre el hiperparatiroidismo y la infección de las vías urinarias por Salmonella. Damos a conocer aquí el caso de un hombre de 37 años con una historia de hiperparatiroidismo primario y nefrocalcinosis bilateral, que desarrolló una infección de las vías urinarias. La Salmonella del grupo D fue aislada de su muestra de orina. La Salmonella se debe considerar como un posible organismo de causalidad en pacientes con hiperparatiroidismo primario y nefrocalcinosis que desarrollan infección del tracto urinario. Estos pacientes necesitan tomar conciencia de los riesgos potenciales asociados con la salmonellosis.

Human placental multipotent mesenchymal stromal cells modulate trophoblast migration via Rap1 activation.

INTRODUCTION: Little is known about the interaction between human placental multipotent mesenchymal stromal cell (hPMSC) and trophoblast. We hypothesize that hPMSCs produce hepatocyte growth factor (HGF) which may interact with trophoblasts and regulate their migration during placentation. METHODS: hPMSCs were isolated from term placentas and conditioned medium was collected after 2 days of culture in hypoxic (<1% O2) or control (20% O2) conditions. Selective agonist and inhibitor or siRNA for protein kinase A (PKA) or Rap1 were combined with Rap1-GTP pull down assays, flow cytometry, integrin ß1 activation assays and adhesion and migration studies to investigate HGF signaling effects in trophoblasts. The hPMSC abundance and HGF level in preeclamptic placentas were compared with gestational age-matched controls. RESULTS: HGF was expressed by hPMSCs and was decreased in hypoxia. HGF induced cAMP production and Rap1 activation in trophoblasts, which in turn activated integrin ß1. The HGF and PKA activator 6-Bnz-cAMP induced Rap1 activation with increased trophoblast adhesion and migration. The alterations were inhibited by PKA inhibitor H89 or Rap1 siRNA. HGF and cAMP expression were reduced in preeclamptic placentas. hPMSC number was decreased in preeclamptic placenta compared to controls (0.68 ± 0.1% vs. 1.32 ± 0.5%; P = 0.026). hPMSC conditioned medium enhanced trophoblast migration which was inhibited by c-Met blocking antibody, but migration was reduced by conditioned medium from hPMSC cultured in hypoxia. CONCLUSIONS: hPMSCs secrete HGF and increase trophoblast cAMP production. The cAMP effector PKA modulates adhesion and migration of trophoblast via signaling to Rap1 and integrin ß1.