Checklist: Neck computed tomography in non-traumatic emergencies.

Patients attending the emergency department (ED) with cervical inflammatory/infectious symptoms or presenting masses that may involve the aerodigestive tract or vascular structures require a contrast-enhanced computed tomography (CT) scan of the neck. Its radiological interpretation is hampered by the anatomical complexity and pathophysiological interrelationship between the different component systems in a relatively small area. Recent studies propose a systematic evaluation of the cervical structures, using a 7-item checklist, to correctly identify the pathology and detect incidental findings that may interfere with patient management. As a conclusion, the aim of this paper is to review CT findings in non-traumatic pathology of the neck in the ED, highlighting the importance of a systematic approach in its interpretation and synthesis of a structured, complete, and concise radiological report.

Lista de verificación: tomografía computarizada de cuello en urgencias no traumáticas / Checklist: Neck computed tomography in non-traumatic emergencies

A los pacientes que acuden a urgencias con síntomas inflamatorio/infecciosos a nivel cervical o con masas que pueden comprometer el tracto aerodigestivo o las estructuras vasculares, es necesario hacerles una tomografía computarizada (TC) de cuello con contraste. Su interpretación radiológica se ve dificultada por la complejidad anatómica y la interrelación fisiopatológica entre los diferentes sistemas que lo componen, en un área de estudio relativamente pequeña. Estudios recientes proponen realizar una evaluación sistemática de las estructuras cervicales, utilizando para ello un listado de verificación de 7 elementos, para identificar correctamente la patología, y detectar los hallazgos incidentales que pueden interferir en el manejo del paciente. El objetivo de este trabajo es revisar los hallazgos de la TC en la patología no traumática del cuello en urgencias siguiendo una lectura sistemática, tras la cual se pueda realizar un informe radiológico estructurado, completo y conciso.(AU)

Patients attending the emergency department (ED) with cervical inflammatory/infectious symptoms or presenting masses that may involve the aerodigestive tract or vascular structures require a contrast-enhanced computed tomography (CT) scan of the neck. Its radiological interpretation is hampered by the anatomical complexity and pathophysiological interrelationship between the different component systems in a relatively small area. Recent studies propose a systematic evaluation of the cervical structures, using a 7-item checklist, to correctly identify the pathology and detect incidental findings that may interfere with patient management. As a conclusion, the aim of this paper is to review CT findings in non-traumatic pathology of the neck in the ED, highlighting the importance of a systematic approach in its interpretation and synthesis of a structured, complete, and concise radiological report.(AU)

Usefulness of resuscitative endovascular balloon occlusion of the aorta (REBOA) in controlling puerperal bleeding in patients with abnormal placental implantation.

BACKGROUND AND AIMS: Abnormalities of placental implantation, which make up the spectrum of placenta accreta, are associated with high maternal morbidity and mortality due to massive bleeding during delivery. Placing aortic occlusion balloons helps control the bleeding, facilitating surgical intervention. A new device, resuscitative endovascular balloon occlusion of the aorta (REBOA), minimizes the risks and complications associated with the placement of traditional aortic balloons and is also efficacious in controlling bleeding. The aim of this study is to evaluate the usefulness, efficacy, and safety of REBOA in puerperal bleeding due to abnormalities of placental implantation. MATERIAL AND METHODS: Between November 2019 and November 2021, our interventional radiology team placed six REBOA devices in six women scheduled for cesarean section due to placenta accrete. RESULTS: Mean blood loss during cesarean section after REBOA (3507.5 mL) was similar to the amounts reported for other aortic balloons. The mean number of units of packed red blood cells required for transfusion was 3.5. Using REBOA provided the surgical team with adequate conditions to perform the surgery. There were no complications derived from REBOA, and the mean ICU stay was <2 days. CONCLUSION: The technical characteristics of the REBOA device make it a safe and useful alternative for controlling massive bleeding in patients with placenta accreta.

Utilidad de la oclusión aórtica con balón REBOA para el control de las hemorragias puerperales en pacientes con anomalías de la implantación placentaria / Usefulness of resuscitative endovascular balloon occlusion of the aorta (REBOA) in controlling puerperal bleeding in patients with abnormal placental implantation

Antecedentes y objetivo: Las anomalías en la implantación placentaria, que conforman el espectro de la placenta acreta, son causa de alta morbimortalidad maternal por la hemorragia masiva que se produce en estas pacientes durante el parto. La colocación previa de balones de oclusión aórticos ayuda a controlar el sangrado, disminuyéndolo y facilitando la intervención quirúrgica. Existe un nuevo balón de oclusión aórtico denominado REBOA que minimiza los riesgos y las complicaciones asociadas a la colocación de los balones aórticos tradicionales además de lograr el control de las hemorragias. El objetivo del presente estudio es evaluar la utilidad, la eficacia y la seguridad del balón REBOA en las hemorragias puerperales por anomalías en la implantación placentaria. Material y métodos: Desde noviembre del 2019 hasta noviembre del 2021 se han colocado, por parte de radiología intervencionista, 6 balones REBOA en 6 mujeres que iban a ser tratadas mediante cesárea programada de acretismo placentario. Resultado: En el estudio realizado, las pérdidas de volumen sanguíneo durante la cesárea tras la colocación del balón REBOA son similares a las reportadas en la literatura con otros balones aórticos, con una media de 3.507,5ml. La media de requerimientos transfusionales fue de 3,5 concentrados de hematíes. El uso del balón REBOA proporcionó al equipo quirúrgico unas condiciones adecuadas para realizar la cirugía. No hubo complicaciones derivadas de su colocación y la estancia media en UCI de las pacientes fue inferior a 2 días. Conclusión: El balón REBOA, gracias a sus características técnicas, se plantea como una nueva alternativa segura y útil para el control de las hemorragias masivas en las pacientes con acretismo placentario.(AU)

Background and aims: Abnormalities of placental implantation, which make up the spectrum of placenta accreta, are associated with high maternal morbidity and mortality due to massive bleeding during delivery. Placing aortic occlusion balloons helps control the bleeding, facilitating surgical intervention. A new device, resuscitative endovascular balloon occlusion of the aorta (REBOA), minimizes the risks and complications associated with the placement of traditional aortic balloons and is also efficacious in controlling bleeding. The aim of this study is to evaluate the usefulness, efficacy, and safety of REBOA in puerperal bleeding due to abnormalities of placental implantation. Material and methods: Between November 2019 and November 2021, our interventional radiology team placed six REBOA devices in six women scheduled for cesarean section due to placenta accrete. Results Mean blood loss during cesarean section after REBOA (3507.5mL) was similar to the amounts reported for other aortic balloons. The mean number of units of packed red blood cells required for transfusion was 3.5. Using REBOA provided the surgical team with adequate conditions to perform the surgery. There were no complications derived from REBOA, and the mean ICU stay was < 2 days. Conclusion The technical characteristics of the REBOA device make it a safe and useful alternative for controlling massive bleeding in patients with placenta accreta.(AU)

LP2, a stable lanthipeptide derived from cAng-(1-7), exerts myeloprotective action in mice.

OBJECTIVES: Linear unstable angiotensins stimulate hematopoiesis. Here we address: (1) Is cyclic angiotensin-(1-7) myeloprotective in mice? (2) Is cyclic angiotensin-(1-7) stable in rat? (3) Does LP2, a cyclic angiotensin-(1-7) with an N-terminal d-lysine, exert myeloprotective action in tumor-bearing mice? MATERIALS AND METHODS: Cyclic angiotensin-(1-7)'s capacity to restore levels of blood platelets and white blood cells was studied in gemcitabine-treated mice. The stability of cyclic angiotensin-(1-7) in rat was measured in blood samples taken after injection or infusion. The capacity of LP2 to restore total bone marrow cell levels in mice after treatment with 5-fluoruracil was measured. In addition, the capacity of LP2 to counter anemia in tumor-bearing mice treated with erlotinib was measured. RESULTS: Cyclic angiotensin-(1-7) dose-dependently restored blood platelet levels in gemcitabine-treated mice, whereas its capacity to restore levels of white blood cells was less. In vivo aminoterminal breakdown of cyclic angiotensin-(1-7) yielded cyclic angiotensin-(2-7) and cyclic angiotensin-(3-7). LP2 significantly (p < .0001 at 100 µg/kg/day) restored bone marrow cell counts in mice after treatment with 5-fluoruracil. LP2 also significantly (p < .05) countered anemia in tumor-bearing mice treated with erlotinib. CONCLUSIONS: LP2 exerts myeloprotective action with perspectives for continuation of its clinical development.

LP2, a cyclic angiotensin-(1-7) analog extended with an N-terminal D-lysine, impairs growth of patient-derived xenografts of colorectal carcinoma in mice.

LP2 is a 4, 7 D, L lanthionine-stabilized analog of angiotensin-(1-7), with an N-terminal D-lysine, resistant to breakdown by peptidases. It is a specific agonist of the angiotensin II type 2 receptor. Consistent with its high specificity and stability, LP2 has shown excellent safety and pharmacokinetics in a first-in-human clinical phase Ia trial. Here, based on strong rationales, we studied the capacity of LP2 to inhibit the growth of patient-derived xenografts of colorectal cancer in mice. Prior to efficacy studies, immunohistochemistry on an untreated tissue array demonstrated that the AT2R expression is reduced in human colorectal cancer and in stroma when compared to tumor adjacent tissue. Subsequent studies demonstrated that LP2 at a subcutaneously injected dose as low as 0.2 µg/kg/day inhibited patient-derived xenografts of colorectal carcinoma in mice. Kinome analyses and validation of elected kinase inhibition indicated that LP2-mediated AT2R stimulation inhibited PI3K/AKT/mTOR which resulted in apoptosis via CDKs. LP2 acted synergistically with 5-FU and the EGFR inhibitor erlotinib. Taken together, the extremely low dose of LP2 at which antitumor activity is exerted, the synergism with selected drugs and, together with its excellent specificity, safety and stability, warrant further evaluation of LP2's inhibitory potential of colorectal cancer.

Pediatric chest x-ray in covid-19 infection.

BACKGROUND: The outbreak of COVID-19 has become pandemic. Pediatric population has been less studied than adult population and prompt diagnosis is challenging due to asymptomatic or mild episodes. Radiology is an important complement to clinical and epidemiological features. OBJECTIVE: To establish the most common CXR patterns in children with COVID-19, evaluate interobserver correlation and to discuss the role of imaging techniques in the management of children. MATERIALS AND METHODS: Forty-four patients between 0 and 16 years of age with confirmed SARS-Cov-2 infection and CXR were selected. Two paediatric radiologists independently evaluated the images and assessed the type of abnormality, distribution and evolution when available. RESULTS: Median age was 79.8 months (ranging from 2 weeks to 16 years of age). Fever was the most common symptom (43.5 %). 90 % of CXR showed abnormalities. Peribronchial cuffing was the most common finding (86.3 %) followed by GGOs (50 %). In both cases central distribution was more common than peripheral. Consolidations accounted for 18.1 %. Normal CXR, pleural effusion, and altered cardiomediastinal contour were the least common. CONCLUSION: The vast majority of CXR showed abnormalities in children with COVID-19. However, findings are nonspecific. Interobserver correlation was good in describing consolidations, normal x-rays and GGOs. Imaging techniques have a role in the management of children with known or suspected COVID-19, especially in those with moderate or severe symptoms or with underlying risk factors.

Radiation dose optimisation for conventional imaging in infants and newborns using automatic dose management software: an application of the new 2013/59 EURATOM directive.

Objective: The new 2013/59 EURATOM Directive (ED) demands dosimetric optimisation procedures without undue delay. The aim of this study was to optimise paediatric conventional radiology examinations applying the ED without compromising the clinical diagnosis. METHODS: Automatic dose management software (ADMS) was used to analyse 2678 studies of children from birth to 5 years of age, obtaining local diagnostic reference levels (DRLs) in terms of entrance surface air kerma. Given local DRL for infants and chest examinations exceeded the European Commission (EC) DRL, an optimisation was performed decreasing the kVp and applying the automatic control exposure. To assess the image quality, an analysis of high-contrast resolution (HCSR), signal-to-noise ratio (SNR) and figure of merit (FOM) was performed, as well as a blind test based on the generalised estimating equations method. RESULTS: For newborns and chest examinations, the local DRL exceeded the EC DRL by 113%. After the optimisation, a reduction of 54% was obtained. No significant differences were found in the image quality blind test. A decrease in SNR (-37%) and HCSR (-68%), and an increase in FOM (42%), was observed. CONCLUSION: ADMS allows the fast calculation of local DRLs and the performance of optimisation procedures in babies without delay. However, physical and clinical analyses of image quality remain to be needed to ensure the diagnostic integrity after the optimisation process. Advances in knowledge: ADMS are useful to detect radiation protection problems and to perform optimisation procedures in paediatric conventional imaging without undue delay, as ED requires.

Cue reactivity towards bodies in anorexia nervosa - common and differential effects in adolescents and adults.

BACKGROUND: Aberrant reward mechanisms with regard to slim body shapes are discussed in patients with anorexia nervosa (AN). The aim of the present study was to examine of cue reactivity toward body shapes in AN via the late positive potential (LPP), an event-related electroencephalography (EEG) component. By including adolescents and adults, aspects of development and chronification could be studied (2 × 2 design). METHODS: Thirty-two female AN patients (19 adolescents and 13 adults) and 37 control participants (16 adolescents and 21 adults) were included. Standardized photographic stimuli showing women's bodies in underwear from five body mass index (BMI) categories (extremely underweight to extremely overweight) were presented. During picture evaluation, EEG activity was recorded (10-20 system). The LPP was measured in two time windows characterized by different topographies (450-700 ms: posterior; 1000-1300 ms: central). RESULTS: Regarding the posterior component, LPP amplitudes were clearly reduced in adult but not in adolescent patients; for both time windows the LPP showed differential patterns over BMI categories for patients and controls. Regarding the central component, a highly significant linear decrease from extremely underweight to extremely overweight body shapes was revealed in patients and no significant modulation in control participants. CONCLUSIONS: Adolescent and adult patients show increased sustained attention toward extremely underweight bodies. In chronically ill patients, this bias appears to be accompanied by generally reduced automatic attention. The LPP findings provide a differentiated picture of aberrant cue reactivity which could be interpreted as motivated attention toward body shapes in AN.

Prenatal and adult androgen activities in alcohol dependence.

OBJECTIVE: Alcohol dependence is more prevalent in men than in women. The evidence for how prenatal and adult androgens influence alcohol dependence is limited. We investigated the effects of prenatal and adult androgen activity on alcohol dependence. Moreover, we studied how the behaviours of pregnant women affect their children's prenatal androgen load. METHOD: We quantified prenatal androgen markers (e.g., second-to-fourth finger length ratio [2D : 4D]) and blood androgens in 200 early-abstinent alcohol-dependent in-patients and 240 controls (2013-2015, including a 12-month follow-up). We also surveyed 134 women during pregnancy (2005-2007) and measured the 2D : 4D of their children (2013-2016). RESULTS: The prenatal androgen loads were higher in the male alcohol-dependent patients compared to the controls (lower 2D : 4D, P = 0.004) and correlated positively with the patients' liver transaminase activities (P < 0.001) and alcohol withdrawal severity (P = 0.019). Higher prenatal androgen loads and increasing androgen levels during withdrawal predicted earlier and more frequent 12-month hospital readmission in alcohol-dependent patients (P < 0.005). Moreover, stress levels (P = 0.002), alcohol (P = 0.010) and tobacco consumption (P = 0.017), and lifetime stressors (P = 0.019) of women during pregnancy related positively to their children's prenatal androgen loads (lower 2D : 4D). CONCLUSION: Androgen activities in alcohol-dependent patients and behaviours of pregnant women represent novel preventive and therapeutic targets of alcohol dependence.

Stress system dysregulation in pediatric generalized anxiety disorder associated with comorbid depression.

Because chronic stress is an important risk factor for anxiety states and depressive disorders, we studied hypothalamus-pituitary-adrenal (HPA) axis and sympathetic system activity via changes in cortisol and alpha amylase activity levels in pediatric generalized anxiety disorder (GAD) patients (n = 26) with comorbid depression and a healthy comparison group (n = 26). Morning plasma cortisol and diurnal profiles of salivary cortisol and salivary alpha amylase (sAA) activity were assessed, also reactivity of HPA-axis, sAA activity, and heart rate following a psychosocial stressor (Trier Social Stress Test for children). GAD patients with comorbid depression showed increased morning plasma and salivary cortisol levels, ameliorating throughout in-patient treatment, and higher sAA activity in their diurnal profile. Both HPA and sympathetic activity positively correlated with the severity of anxiety and depression. We also demonstrated a blunted HPA and sympathetic response to acute stress in patients. This pattern of neuroendocrine and sympathetic changes seems to be distinct from the one previously reported in pediatric patients with only social anxiety or depressive disorders. We propose morning plasma and saliva cortisol levels as potential physiological indicators for supporting the evaluation of symptoms' severity and treatment progress in children with GAD and comorbid depressive disorder.

Iodine status and thyroid function among Spanish schoolchildren aged 6-7 years: the Tirokid study.

I deficiency is still a worldwide public health problem, with children being especially vulnerable. No nationwide study had been conducted to assess the I status of Spanish children, and thus an observational, multicentre and cross-sectional study was conducted in Spain to assess the I status and thyroid function in schoolchildren aged 6-7 years. The median urinary I (UI) and thyroid-stimulating hormone (TSH) levels in whole blood were used to assess the I status and thyroid function, respectively. A FFQ was used to determine the consumption of I-rich foods. A total of 1981 schoolchildren (52 % male) were included. The median UI was 173 µg/l, and 17·9 % of children showed UI<100 µg/l. The median UI was higher in males (180·8 v. 153·6 µg/l; P<0·001). Iodised salt (IS) intake at home was 69·8 %. IS consumption and intakes of ≥2 glasses of milk or 1 cup of yogurt/d were associated with significantly higher median UI. Median TSH was 0·90 mU/l and was higher in females (0·98 v. 0·83; P<0·001). In total, 0·5 % of children had known hypothyroidism (derived from the questionnaire) and 7·6 % had TSH levels above reference values. Median TSH was higher in schoolchildren with family history of hypothyroidism. I intake was adequate in Spanish schoolchildren. However, no correlation was found between TSH and median UI in any geographical area. The prevalence of TSH above reference values was high and its association with thyroid autoimmunity should be determined. Further assessment of thyroid autoimmunity in Spanish schoolchildren is desirable.

Effects of In utero environment and maternal behavior on neuroendocrine and behavioral alterations in a mouse model of prenatal trauma.

Maternal posttraumatic stress disorder (PTSD) following trauma exposure during pregnancy is associated with an increased risk of affective disorders in children. To investigate the mechanisms by which prenatal trauma and/or maternal PTSD affect brain development and behavior we established a mouse model of prenatal traumatic (PT) experience based on the application of an electric foot shock to C57Bl/6N female mice on the gestational day 12 during their pregnancy. The model is based on a previously validated animal model of PTSD. We found high anxiety levels and poor maternal care along with reduced serum prolactin and increased corticosterone levels in dams following maternal trauma (MT). PT-pups were born smaller and stayed smaller throughout their life. We show increased time and frequency of ultrasonic calls in PT-pups when separated from the mothers on the postnatal day (PND) 9. Cross-fostering experiments reveal lower anxiety levels in PT pups raised by healthy mothers as compared to trauma-naive pups raised by MT-dams. Importantly, the combination of prenatal trauma and being raised by a traumatized mother leads to: (1) the highest corticosterone levels in pups, (2) longest USV-call time and (3) highest anxiety levels in comparison to other experimental groups. Our data indicates a distinct change in maternal care following MT which is possibly associated with trauma-induced decrease in prolactin levels. Furthermore, we show that maternal behavior is crucial for the development of the offspring anxiety and specific aspects in maternal care overwrite to a significant extend the effects of in utero and postnatal environment. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1254-1265, 2016.

GRPR-selective PET imaging of prostate cancer using [(18)F]-lanthionine-bombesin analogs.

The gastrin-releasing peptide receptor (GRPR) is overexpressed in a variety of human malignancies, including prostate cancer. Bombesin (BBN) is a 14 amino acids peptide that selectively binds to GRPR. In this study, we developed two novel Al(18)F-labeled lanthionine-stabilized BBN analogs, designated Al(18)F-NOTA-4,7-lanthionine-BBN and Al(18)F-NOTA-2,6-lanthionine-BBN, for positron emission tomography (PET) imaging of GRPR expression using xenograft prostate cancer models. (Methyl)lanthionine-stabilized 4,7-lanthionine-BBN and 2,6-lanthionine-BBN analogs were conjugated with a NOTA chelator and radiolabeled with Al(18)F using the aluminum fluoride strategy. Al(18)F-NOTA-4,7-lanthionine-BBN and Al(18)F-NOTA-2,6-lanthionine-BBN was labeled with Al(18)F with good radiochemical yield and specific activity>30 GBq/µmol for both radiotracers. The logD values measured for Al(18)F-NOTA-4,7-lanthionine-BBN and Al(18)F-NOTA-2,6-lanthionine-BBN were -2.14 ± 0.14 and -2.34 ± 0.15, respectively. In athymic nude PC-3 xenografts, at 120 min post injection (p.i.), the uptake of Al(18)F-NOTA-4,7-lanthionine-BBN and Al(18)F-NOTA-2,6-lanthionine-BBN in prostate cancer (PC-3) mouse models was 0.82 ± 0.23% ID/g and 1.40 ± 0.81% ID/g, respectively. An excess of unlabeled ɛ-aminocaproic acid-BBN(7-14) (300-fold) was co-injected to assess GRPR binding specificity. Tumor uptake of Al(18)F-NOTA-4,7-lanthionine-BBN and Al(18)F-NOTA-2,6-lanthionine-BBN in PC-3 tumors was evaluated by microPET (µPET) imaging at 30, 60 and 120 min p.i. Blocking studies showed decreased uptake in PC-3 bearing mice. Stabilized 4,7-lanthionine-BBN and 2,6-lanthionine-BBN peptides were rapidly and successfully labeled with (18)F. Both tracers may have potential for GRPR-positive tumor imaging.

αCaMKII controls the establishment of cocaine's reinforcing effects in mice and humans.

Although addiction develops in a considerable number of regular cocaine users, molecular risk factors for cocaine dependence are still unknown. It was proposed that establishing drug use and memory formation might share molecular and anatomical pathways. Alpha-Ca(2+)/calmodulin-dependent protein kinase-II (αCaMKII) is a key mediator of learning and memory also involved in drug-related plasticity. The autophosphorylation of αCaMKII was shown to accelerate learning. Thus, we investigated the role of αCaMKII autophosphorylation in the time course of establishing cocaine use-related behavior in mice. We found that αCaMKII autophosphorylation-deficient αCaMKII(T286A) mice show delayed establishment of conditioned place preference, but no changes in acute behavioral activation, sensitization or conditioned hyperlocomotion to cocaine (20 mg kg(-1), intraperitoneal). In vivo microdialysis revealed that αCaMKII(T286A) mice have blunted dopamine (DA) and blocked serotonin (5-HT) responses in the nucleus accumbens (NAcc) and prefrontal cortex after acute cocaine administration (20 mg kg(-1), intraperitoneal), whereas noradrenaline responses were preserved. Under cocaine, the attenuated DA and 5-HT activation in αCaMKII(T286A) mice was followed by impaired c-Fos activation in the NAcc. To translate the rodent findings to human conditions, several CAMK2A gene polymorphisms were tested regarding their risk for a fast establishment of cocaine dependence in two independent samples of regular cocaine users from Brazil (n=688) and Switzerland (n=141). A meta-analysis across both samples confirmed that CAMK2A rs3776823 TT-allele carriers display a faster transition to severe cocaine use than C-allele carriers. Together, these data suggest that αCaMKII controls the speed for the establishment of cocaine's reinforcing effects.

11Beta-hydroxylase deficiency and other syndromes of mineralocorticoid excess as a rare cause of endocrine hypertension.

Hypertension represents a major public and global health problem, most of which likely can be improved by lifestyle changes including changing dietary habits with less consumption of processed and preserved foods, which generally contain higher amounts of salt than freshly prepared food items. Among causes for endocrine hypertension are syndromes of mineralocorticoid excess. This group of mostly monogenic and acquired disorders typically causes hypertension through activation of the mineralocorticoid receptor either directly or indirectly via hormonal mediators and from overactive amiloride-sensitive epithelial sodium channels located in the distal tubule and collecting ducts of the kidneys. Apart from primary aldosteronism, mineralocorticoid excess can be caused by congenital adrenal hyperplasia (CAH) due to mutations of the 11beta-hydroxylase and 17alpha-hydroxylase genes, by inactivating mutations of the glucocorticoid receptor gene (Chrousos syndrome), endogenous hypercortisolism (Cushing's syndrome), by mutations of the 11beta-hydroxysteroid dehydrogenase type 2 gene (apparent mineralocorticoid excess/AME) or licorice/carbenoxolone intake, mutations of the epithelial sodium channel genes (Liddle syndrome), mutations of the mineralocorticoid receptor gene (Geller syndrome), and by mutations in the WNK1, WNK4, KLHL3, CUL3 genes (pseudohypoaldosteronism type 2 or Gordon syndrome). Most of these conditions are treated by restricting dietary salt intake. However, some require special therapies including dexamethasone/hydrocortisone (CAH), spironolactone/eplerenone (AME), epithelial sodium channel inhibitors amiloride/triamterene (Liddle and Gordon syndrome), while in others spironolactone and MR antagonists may be contraindicated due to an abnormally structured MR (Geller syndrome). We here review the pathophysiology, diagnosis, and therapy of these rare conditions including the presentation of a patient with 11beta-hydroxylase deficiency.

Bone repair using periodontal ligament progenitor cell-seeded constructs.

The success of tissue-engineering therapies is dependent on the ability of scaffolds to guide differentiation of progenitor cells. Here we present a new approach using a biomimetic construct composed of hydroxyapatite modified with an in vitro-derived extracellular matrix (HA-ECM) and seeded with periodontal ligament progenitor cells (PDLCs). The study aimed to investigate the effect of HA-ECM on osteogenic differentiation of PDLCs and in vivo evaluation of the PDLC-seeded HA-ECM constructs using a rat calvarial critical-sized defect model. After flow-cytometric phenotyping of PDLCs for typical mesenchymal stem cell markers, the PDLCs were cultured on HA-ECM or HA alone in osteogenic media and assessed by MTT, alkaline phosphatase (ALP) assays, and real-time qPCR at different time intervals after seeding. New bone formation induced by PDLC-seeded constructs was assessed by histomorphometric analysis at 12 weeks post-operatively. The PDLCs seeded on HA-ECM showed significantly higher ALP activity and up-regulation of bone-related genes. The treatment with PDLC-seeded HA-ECM significantly improved calvarial bone repair, with the highest amount of newly formed bone elicited by cell-seeded constructs cultured for 14 days. Our results highlight the PDLC-seeded HA-ECM constructs as a promising tool for craniofacial bone regeneration.

Analysis of tissues following mesenchymal stromal cell therapy in humans indicates limited long-term engraftment and no ectopic tissue formation.

Mesenchymal stromal cells (MSCs) are explored as a novel treatment for a variety of medical conditions. Their fate after infusion is unclear, and long-term safety regarding malignant transformation and ectopic tissue formation has not been addressed in patients. We examined autopsy material from 18 patients who had received human leukocyte antigen (HLA)-mismatched MSCs, and 108 tissue samples from 15 patients were examined by PCR. No signs of ectopic tissue formation or malignant tumors of MSC-donor origin were found on macroscopic or histological examination. MSC donor DNA was detected in one or several tissues including lungs, lymph nodes, and intestine in eight patients at levels from 1/100 to <1/1,000. Detection of MSC donor DNA was negatively correlated with time from infusion to sample collection, as DNA was detected from nine of 13 MSC infusions given within 50 days before sampling but from only two of eight infusions given earlier. There was no correlation between MSC engraftment and treatment response. We conclude that MSCs appear to mediate their function through a "hit and run" mechanism. The lack of sustained engraftment limits the long-term risks of MSC therapy.

Tissue-engineered airway: a regenerative solution.

The use of synthetic degradable or permanent polymers and biomaterials has not yet helped to achieve successful clinical whole-airway replacement. A novel, clinically successful approach involves tissue engineering (TE) replacement using three-dimensional biologic scaffolds composed of allogeneic extracellular scaffolds derived from nonautologous sources and recellularized with autologous stem cells or differentiated cells. In this paper, we discuss this novel approach and review information that can lead to a better understanding of stem cell recruitment and/or mobilization and site-specific tissue protection, which can be pharmacologically boosted in humans.