M-CSF as a therapeutic target in BRAFV600E melanoma resistant to BRAF inhibitors.

BACKGROUND: Disseminated BRAFV600E melanoma responds to BRAF inhibitors (BRAFi) but easily develops resistance with poor prognosis. Secretome plays a pivotal role during tumour progression causing profound effects on therapeutic efficacy. Secreted M-CSF is involved in both cytotoxicity suppression and tumour progression in melanoma. We aimed to analyse the M-CSF contribution in resistant metastatic melanoma to BRAF-targeted therapies. METHODS: Conditioned media from melanoma cells were analysed by citoarray. Viability and migration/invasion assays were performed with paired melanoma cells and tumour growth in xenografted SCID mice. We evaluated the impact of M-CSF plasma levels with clinical prognosis from 35 metastatic BRAFV600E-mutant melanoma patients. RESULTS: BRAFi-resistant melanoma cells secretome is rich in pro-tumour cytokines. M-CSF secretion is essential to induce a Vemurafenib-resistant phenotype in melanoma cells. Further, we demonstrated that M-CSF mAb in combination with Vemurafenib and autophagy blockers synergistically induce apoptosis, impair migration and reduce tumour growth in BRAFi-resistant melanoma cells. Interestingly, lower M-CSF plasma levels are associated with better prognosis in metastatic melanoma patients. CONCLUSIONS: Secreted M-CSF induces a BRAFi-resistant phenotype and means worse prognosis in BRAFV600E metastatic melanoma patients. These results identify secreted M-CSF as a promising therapeutic target toward BRAFi-resistant melanomas.

Direct Constraints on the Ultralight Boson Mass from Searches of Continuous Gravitational Waves.

Superradiance can trigger the formation of an ultralight boson cloud around a spinning black hole. Once formed, the boson cloud is expected to emit a nearly periodic, long-duration, gravitational-wave signal. For boson masses in the range (10^{-13}-10^{-11}) eV, and stellar mass black holes, such signals are potentially detectable by gravitational-wave detectors, like Advanced LIGO and Virgo. In this Letter, we present full band upper limits for a generic all-sky search for periodic gravitational waves in LIGO O2 data, and use them to derive-for the first time-direct constraints on the ultralight scalar boson field mass.

Defective glucose and lipid metabolism in rheumatoid arthritis is determined by chronic inflammation in metabolic tissues.

BACKGROUND: Rheumatoid arthritis (RA) patients are at increased risk of insulin resistance (IR); however, the specific mechanisms mediating this association are currently unknown. OBJECTIVE: To investigate whether the inflammatory activity associated with RA accounts for the observed defective glucose metabolism and lipid metabolism in these patients. METHODS: We followed two main strategies: (i) extensive metabolic profiling of a RA cohort of 100 patients and 50 healthy control subjects and (ii) mechanistic studies carried out in both a collagen-induced arthritis mouse model and 3T3-L1 adipocytes treated with conditioned serum from RA patients. RESULTS: Following the exclusion of obese and diabetic subjects, data from RA patients demonstrated a strong link between the degree of systemic inflammation and the development of IR. These results were strengthened by the observation that induction of arthritis in mice resulted in a global inflammatory state characterized by defective carbohydrate and lipid metabolism in different tissues. Adipose tissue was most susceptible to the RA-induced metabolic alterations. These metabolic effects were confirmed in adipocytes treated with serum from RA patients. CONCLUSIONS: Our results show that the metabolic disturbances associated with RA depend on the degree of inflammation and identify inflammation of adipose tissue as the initial target leading to IR and the associated molecular disorders of carbohydrate and lipid homeostasis. Thus, we anticipate that therapeutic strategies based on tighter control of inflammation and flares could provide promising approaches to normalize and/or prevent metabolic alterations associated with RA.

Diagnostic potential of NETosis-derived products for disease activity, atherosclerosis and therapeutic effectiveness in Rheumatoid Arthritis patients.

OBJECTIVES: 1) To assess the association of NETosis and NETosis-derived products with the activity of the disease and the development of cardiovascular disease in RA; 2) To evaluate the involvement of NETosis on the effects of biologic therapies such as anti-TNF alpha (Infliximab) and anti-IL6R drugs (Tocilizumab). METHODS: One hundred and six RA patients and 40 healthy donors were evaluated for the occurrence of NETosis. Carotid-intimae media thickness was analyzed as early atherosclerosis marker. Inflammatory and oxidative stress mediators were quantified in plasma and neutrophils. Two additional cohorts of 75 RA patients, treated either with Infliximab (n = 55) or Tocilizumab (n = 20) for six months, were evaluated. RESULTS: NETosis was found increased in RA patients, beside myeloperoxidase and neutrophil elastase protein levels. Cell-free nucleosomes plasma levels were elevated, and strongly correlated with the activity of the disease and the positivity for autoantibodies, alongside inflammatory and oxidative profiles in plasma and neutrophils. Moreover, ROC analyses showed that cell-free nucleosomes levels could identify RA patients showing early atherosclerosis with high specificity. RA patients treated either with IFX or TCZ for six months exhibited decreased generation of NETs. Concomitantly, clinical parameters and serum markers of inflammation were found reduced. Mechanistic in vitro analyses showed that inhibition of NETs extrusion by either DNase, IFX or TCZ, further abridged the endothelial dysfunction and the activation of immune cells, thus influencing the global activity of the vascular system. CONCLUSIONS: NETosis-derived products may have diagnostic potential for disease activity and atherosclerosis, as well as for the assessment of therapeutic effectiveness in RA.

Decoding clinical and molecular pathways of liver dysfunction in Psoriatic Arthritis: Impact of cumulative methotrexate doses.

BACKGROUND: The occurrence of liver abnormalities in Psoriatic Arthritis (PsA) has gained significant recognition. Identifying key factors at the clinical and molecular level can help to detect high-risk patients for non-alcoholic fatty liver disease in PsA. OBJECTIVES: to investigate the influence of PsA and cumulative doses of methotrexate on liver function through comprehensive in vivo and in vitro investigations. METHODS: A cross-sectional study involving 387 subjects was conducted, 200 patients with PsA, 87 NAFLD-non-PsA patients, and 100 healthy donors (HDs), age and sex-matched. Additionally, a retrospective longitudinal study was carried out, including 83 PsA patients since initiation with methotrexate. Detailed clinical, and laboratory parameters along with liver disease risk were analyzed. In vitro, experiments with hepatocyte cell line (HEPG2) were conducted. RESULTS: PsA patients present increased liver disease risk associated with the presence of cardiometabolic comorbidities, inflammatory markers, onychopathy, and psoriasis. The treatment with PsA serum on hepatocytes encompassed inflammatory, fibrotic, cell stress, and apoptotic processes. At the molecular level, methotrexate impacts liver biology, although the cumulative doses did not affect those alterations, causing any potential damage to liver function at the clinical level. Finally, anti-PDE-4 or anti-JAK decreased the inflammatory profile induced by PsA serum on hepatocytes. CONCLUSION: 1)This study identifies the complex link between liver disease risk, comorbidities, and disease-specific features in PsA patients. 2)Methotrexate dose in PsA patients had no significant effect on liver parameters, confirmed by hepatocyte in vitro studies. 3)Anti-PDE-4 and anti-JAK therapies show promise in reducing PsA serum-induced hepatocyte activation, potentially aiding liver complication management.

Women in urology: what is their current situation in Spain?

OBJECTIVE: To analyze the current state of women in urology in Spain. MATERIAL AND METHODS: Descriptive study based on the results of an online survey sent between February and April 2020 through the database of the Residents and Young Urologists group (RAEU) of the Spanish Association of Urology (AEU). Characteristics of the survey and its results were analyzed. RESULTS: In total, 257 responses were obtained from 210 women (81.71%) and 47 men (18.29%) belonging to 111 hospitals. Statistically significant differences were observed (p < 0.001) with a higher proportion of men in all categories except for the group of young female and male attendings (29-39 years, p = 0.789), and the group of female residents against male residents (p = 0.814). The number of men was higher in hospitals with subspecialty units except for the Pelvic Floor Unit, where no statistically significant difference was observed (p = 0.06). Regarding positions of responsibility, only 7 out of 111 hospitals had female Department Chiefs. CONCLUSIONS: Women's representation in urology is increasing, mainly due to the younger generations. However, the access of these women to relevant positions is anecdotal.

Clinical features and immune mechanisms directly linked to the altered liver function in patients with rheumatoid arthritis.

BACKGROUND: The aim of this study was to explore the impact of arthritis on liver function using different approaches in vivo and in vitro. METHODS: A cross-sectional study was performed on 330 non-obese/non-T2DM subjects: 180 RA patients, 50 NAFLD non-RA patients, and 100 healthy donors (HDs). A longitudinal study was conducted on 50 RA patients treated with methotrexate for six months. Clinical and laboratory parameters and markers of liver disease were collected. Mechanistic studies were carried out in both the CIA mouse model and hepatocytes treated with anti-citrullinated protein antibodies (ACPAs). RESULTS: RA patients have an increased risk of suffering from liver disease independent of obesity or T2DM. This risk was associated with factors such as insulin resistance, autoantibodies, inflammation, and component C3. Methotrexate treatment for six months was associated with liver abnormalities in those newly-diagnosed patients having CV risk factors. ACPAs induced a defective hepatocyte function, promoting IR and inflammation. The induction of arthritis in mice caused the infiltration of immune cells in the liver and increased inflammatory, apoptotic, and fibrotic processes. CONCLUSION: RA patients may experience mild to moderate liver inflammation due to the infiltration of T, B cells, and macrophages, and the action of ACPAs. This is independent of obesity or diabetes and linked to systemic inflammation, and disease activity levels. The negative effects of methotrexate on liver function could be restricted to the concomitant presence of cardiovascular risk factors.

Lithium salts as a treatment for COVID-19: Pre-clinical outcomes.

INTRODUCTION: Identifying effective drugs for Coronavirus disease 2019 (COVID-19) is urgently needed. An efficient approach is to evaluate whether existing approved drugs have anti-SARS-CoV-2 effects. The antiviral properties of lithium salts have been studied for many years. Their anti-inflammatory and immune-potentiating effects result from the inhibition of glycogen synthase kinase-3. AIMS: To obtain pre-clinical evidence on the safety and therapeutic effects of lithium salts in the treatment of COVID-19. RESULTS: Six different concentrations of lithium, ranging 2-12 mmol/L, were evaluated. Lithium inhibited the replication of SARS-CoV-2 virus in a dose-dependent manner with an IC50 value of 4 mmol/L. Lithium-treated wells showed a significantly higher percentage of monolayer conservation than viral control, particularly at concentrations higher than 6 mmol/L, verified through microscopic observation, the neutral red assay, and the determination of N protein in the supernatants of treated wells. Hamsters treated with lithium showed less intense disease with fewer signs. No lithium-related mortality or overt signs of toxicity were observed during the experiment. A trend of decreasing viral load in nasopharyngeal swabs and lungs was observed in treated hamsters compared to controls. CONCLUSIONS: These results provide pre-clinical evidence of the antiviral and immunotherapeutic effects of lithium against SARS-CoV-2, which supports an advance to clinical trials on COVID-19's patients.

The use of photoperiod-treated bucks to induce a "male effect" does not compensate for the negative effects of nutritional restriction of the females in Mediterranean goats.

This work examined the effect of acute nutritional restriction or supplementation one week before male introduction on the reproductive performances of the "male effect" when using photostimulated or control males in goats. On 22 March, 84 anoestrous does were placed with photostimulated bucks or with bucks which had received no treatments. One week before male introduction, the females were provided with different nutritional regimes: Supplemented, restricted or control females. The non-esterified fatty acids (NEFAs) and Insulin Growth Factor-1 (IGF-1) concentrations were measured in the same samples. Fecundity, fertility, prolificacy and productivity were also determined. No interaction between both sources of variation was observed in any of the reproductive variables studied. Treatment of the bucks increased the percentage of females expressing behavioural oestrous associated with ovulation (71% vs 90% for Natural and Photo groups, respectively, P < 0.05). The Supplemented females showed higher ovulation rate than Restricted females (1.77 ± 0.13 vs 1.05 ± 0.05, P < 0.001), fecundity (71% vs 43%, P < 0.05); fertility (76% vs 29%, P < 0.05) and productivity (1.00 ± 0.15 vs 0.29 ± 0.11 kids per female, P < 0.01). In the Supplemented females, the higher reproductive results could be due to the lower NEFAs and higher IGF-1 concentrations at ovulation and at the time of oestrus compared to the Restricted females. Thus, the present experiment results demonstrate that nutrition is an important factor in the response to the "male effect" at Mediterranean latitudes, and its negative effect cannot be counterbalanced by using photostimulated bucks.

Protection of ovarian tissue from radiotherapy.

Advances researches in the diagnosis and treatment of childhood, adolescent and adult cancer have greatly increased the life expectancy of premenopausal women with cancer. However, one of the serious side effects of these treatments is the risk of damage to fertility. The ovaries are very sensitive to cytotoxic and radiotherapeutic treatment. The only established method of fertility preservation is embryo cryopreservation according to the Ethics Committee of the American Society for Reproductive Medicine (2005), but this option requires the patient to be of pubertal age, have a partner or use donor sperm, and be able to undergo a cycle of ovarian stimulation, which is not possible when the radiotherapy has to be initiated immediately or when stimulation is contraindicated according to the type of cancer. For patients who need immediate radiotherapy, cryopreservation of ovarian tissue is the only possible alternative. This manuscript reports the different techniques of cryopreservation and the results of transplantation of cryopreserved ovarian tissue. The current techniques allow cryopreservation of human ovarian fragments for a long time with good follicular survival rate after thawing. Numerous studies ultimately in this field have demonstrated to improve the survival rate of the oocytes and cryopreserved follicles. Moreover this manuscript includes a case of a 17-year-old girl who had to undergo pelvic irradiation for non-Hodgkin's lymphoma and the laparoscopic treatment to preserve the fertility (Fig. 2, Ref. 47).

[Organisation of paediatric resident rotations by specific areas]. / Organización de las rotaciones del residente de pediatría por las áreas específicas.

INTRODUCTION: Pediatric resident training is based on rotations. The tutor and the head of the area are responsible for planning the rotation. MATERIAL AND METHODS: An organisational model of rotation for a Pediatric residents program is presented. It includes educational objectives, theoretical contents, abilities and attitudes that must be acquired by the resident, training activities to achieve such objectives, strategies of stimulus and evaluation tools. COMMENTS: The aim of this model is to improve the resident teaching-learning process and help in the planning of resident training for those in charge of pediatric areas.

[Fatal poisoning by accidental inhalation of aluminium phosphide]. / Intoxicación letal por inhalación accidental de fosfuro alumínico.

The cases of two 6 and 9-year-old sisters with lethal poisoning by inhalation of aluminium phosphide, after its inadequate use in a rural environment, are described. The clinical symptoms consisted of sudden vomiting, cardiac arrhythmias, shock, dyspnea, pulmonary edema/acute respiratory distress, metabolic acidosis and hepatic dysfunction, and the patients died in spite of advanced life support. Although an early diagnosis might theoretically improve the poisoning outcome, its high lethality rate and the absence of a specific antidote, efforts must be directed towards prevention and restricting its use as pesticide and being aware of its toxicity.

[Invasive mechanical ventilation in cystic fibrosis: Influence in lung transplant]. / Ventilación mecánica invasiva en fibrosis quística: influencia en el trasplante pulmonar.

INTRODUCTION: Invasive mechanical ventilation (IMV) in patients with advanced cystic fibrosis (CF) is a relative contraindication for lung transplant (LT) in adults, although there is currently no data on children. PATIENTS AND METHODS: An 8-year retrospective study on 21 children with CF who underwent LT was performed, analysing their results as they were receiving (n = 8) or not (n = 13) IMV pretransplant. Demographic and surgical data, postoperative course, lung function and survival (immediate and 1-year) were compared between both groups. The role of the IMV pretransplant as a postoperative risk factor was estimated (odds ratio) and Kaplan Meier survival study was performed in both groups. RESULTS: No differences in patient age, sex and nutritional parameters were observed between both groups. Those on IMV who received LT required more frequent and longer bypass, more need for tracheotomy, a higher number of rejection episodes per patient and multiorgan failure, longer PICU stay and longer time on IMV than those who were not on IMV when LT was received. Nevertheless, no differences could be found regarding graft function and immediate and 1-year survivals (62.5% vs. 92.3% with and without IMV respectively). On the other hand, long-term survival was significantly lower than in patients on IMV. CONCLUSIONS: In our experience, children with CF on IMV who receive LT have more complicated surgery and immediate postoperative course. Though immediate and 1-year results and survivals may be encouraging, medium and long-term ones are significantly lower.

Evaluation of the vasoactive-inotropic score, mid-regional pro-adrenomedullin and cardiac troponin I as predictors of low cardiac output syndrome in children after congenital heart disease surgery.

OBJECTIVE: To determine the predictive value of the inotropic score (IS) and vasoactive-inotropic score (VIS) in low cardiac output syndrome (LCOS) in children after congenital heart disease surgery involving cardiopulmonary bypass (CPB), and to establish whether mid-regional pro-adrenomedullin (MR-proADM) and cardiac troponin I (cTn-I), associated to the IS and VIS scores, increases the predictive capacity in LCOS. DESIGN: A prospective observational study was carried out. SETTING: A Paediatric Intensive Care Unit. PATIENTS: A total of 117children with congenital heart disease underwent CPB. Patients were divided into two groups: LCOS and non-LCOS. INTERVENTIONS: The clinical and analytical data were recorded at 2, 12, 24 and 48h post-CPB. Logistic regression was used to develop a risk prediction model using LCOS as dependent variable. MAIN OUTCOME MEASURES: LCOS, IS, VIS, MR-proADM, cTn-I, age, sex, CPB time, PIM-2, Aristotle score. RESULTS: While statistical significance was not recorded for IS in the multivariate analysis, VIS was seen to be independently associated to LCOS. On the other hand, VIS>15.5 at 2h post-CPB, adjusted for age and CPB timepoints, showed high specificity (92.87%; 95%CI: 86.75-98.96) and increased negative predictive value (75.59%, 95%CI: 71.1-88.08) for the diagnosis of LCOS at 48h post-CPB. The predictive power for LCOS did not increase when VIS was combined with cTn-I >14ng/ml at 2h and MR-proADM >1.5nmol/l at 24h post-CPB. CONCLUSIONS: The VIS score at 2h post-CPB was identified as an independent early predictor of LCOS. This predictive value was not increased when associated with LCOS cardiac biomarkers. The VIS score was more useful than IS post-CPB in making early therapeutic decisions in clinical practice post-CPB.

[Infant botulism]. / Botulismo del lactante.

We report a case of botulism in a 40 day old infant. The patient presented a descending flaccid paralysis requiring mechanical ventilation for 12 days. She is the first European patient treated with Human Botulism Immune Globulin. A few weeks later a second case of infant botulism was detected in our geographical region in Southern Spain. We emphasise the importance of an early diagnosis and treatment with Human Botulism Immune Globulin to decrease morbidity.

'Atherothrombosis-associated microRNAs in Antiphospholipid syndrome and Systemic Lupus Erythematosus patients'.

MicroRNAs markedly affect the immune system, and have a relevant role in CVD and autoimmune diseases. Yet, no study has analyzed their involvement in atherothrombosis related to APS and SLE patients. This study intended to: 1) identify and characterize microRNAs linked to CVD in APS and SLE; 2) assess the effects of specific autoantibodies. Six microRNAs, involved in atherothrombosis development, were quantified in purified leukocytes from 23 APS and 64 SLE patients, and 56 healthy donors. Levels of microRNAs in neutrophils were lower in APS and SLE than in healthy donors. Gene and protein expression of miRNA biogenesis-related molecules were also reduced. Accordingly, more than 75% of identified miRNAs by miRNA profiling were underexpressed. In monocytes, miR124a and -125a were low, while miR-146a and miR-155 appeared elevated. Altered microRNAs' expression was linked to autoimmunity, thrombosis, early atherosclerosis, and oxidative stress in both pathologies. In vitro treatment of neutrophils, monocytes, and ECs with aPL-IgG or anti-dsDNA-IgG antibodies deregulated microRNAs expression, and decreased miRNA biogenesis-related proteins. Monocyte transfections with pre-miR-124a and/or -125a caused reduction in atherothrombosis-related target molecules. In conclusion, microRNA biogenesis, significantly altered in neutrophils of APS and SLE patients, is associated to their atherothrombotic status, further modulated by specific autoantibodies.

No difference in emergence time and early cognitive function between sevoflurane-fentanyl and propofol-remifentanil in patients undergoing craniotomy for supratentorial intracranial surgery.

Balanced anesthesia with sevoflurane-fentanyl has been widely accepted as anesthetic management for neurosurgery. Propofol-remifentanil regimen has been successfully used in various surgical settings, but a comprehensive comparison of sevoflurane-fentanyl and propofol-remifentanil anesthesia in patients undergoing craniotomy for supratentorial intracranial surgery has not yet been done. The aim of this prospective, randomized, open-label clinical trial was to compare clinical properties of sevoflurane-fentanyl with propofol-remifentanil anesthesia in patients undergoing supratentorial intracranial surgery. The primary endpoint was to compare early postoperative recovery and cognitive functions within the two groups; we also evaluated hemodynamic events, vomiting, shivering, and pain. One hundred twenty patients (64 males; age 15-75 years) were randomized to either total intravenous anesthesia (group T) or sevoflurane anesthesia (group S). Emergence and extubation times and cognitive function (Short Orientation Memory Concentration Test [SOMCT]) were compared in the two groups. Brain swelling, incidence of hypotensive and hypertensive episodes, postoperative vomiting, shivering, and pain were also analyzed. The mean emergence time (12.2 +/- 4.9 minutes for group S versus 12.3 +/- 6.1 minutes for group T; P = 0.92) and extubation time (18.2 +/- 2.3 minutes for group S versus 18.3 +/- 2.1 minutes for group T; P = 0.80) were similar in the two groups. Average SOMCT scores, both 15 minutes after extubation (25.6 +/- 4.9 in group S versus 23.9 +/- 7.5 in group T; P = 0.14) and 45 minutes after extubation (27.3 +/- 2.2 in group S versus 26.0 +/- 5.1 in group T; P = 0.07) were also comparable. Brain swelling was present in seven and five patients in groups S and T, respectively (P = 0.76). Hypotension was present in 12% (group S) and 28% (group T) of patients (P = 0.02). Hypertension was present in 17% of patients in group S and 40% of patients in group T (P = 0.0046). Shivering was present in 18% and 25% of patients in groups T and S (P = 0.37). Our study demonstrates that there is no patient benefit of using total intravenous anesthesia with an ultra-short-acting opioid over the conventional balanced volatile technique in terms of recovery and cognitive functions.

[Artificial nutrition in pediatric intensive care units]. / Nutrición artificial en las unidades de cuidados intensivos pediátricos.

OBJECTIVE: To perform an epidemiologic study of artificial nutrition in critically-ill pediatric patients. PATIENTS AND METHODS: A multicenter, prospective and descriptive study was conducted in 23 Spanish intensive care units (ICU) (18 pediatric ICUs and five pediatric/neonatal ICUs) over a 1-month period. Artificial nutrition (AN) was required by 165 critically-ill patients (21.4 %). Data on diagnosis, severity, treatment, type of nutrition administered and complications were analyzed. RESULTS: A total of 54.4 % of the participants were younger than 1 year, 19.4 % were aged between 1 and 5 years old, 15.7 % between 5 and 10 years old and 13.4 % were older than 10 years. ICU mean length stay was 11 days. One hundred six patients were administered enteral nutrition (EN): 67.9 % continuous nasogastric EN, 27.4 intermittent nasogastric EN, 16 % nasojejunal EN, 2.8 % gastrostomy EN. Eighty patients required parenteral nutrition (PN): 86.3 % central PN, 20 % peripheral PN. No significant differences were found between patients with EN and PN in mean energy intake, days receiving AN, diagnosis at admission to the ICU, disease severity (measured by PRISM III) or intensive support techniques. The EN group required greater inotropic support. Patients undergoing mechanical ventilation had equal mortality independent of the type of AN. The most common complications in EN were: 17.9 % emesis, 13.2 % abdominal distension, 11.3 % diarrhea, 4.7 % gastric residual volumes, and 6.6 % hypokalemia. In PN complications consisted of: 5 % catheter related infection, 1.3 % thrombophlebitis, 7.5 % hyponatremia, 3.8 % hypoglycemia, 6.3 % hypophosphatemia and 3.8 % hypertriglyceridemia. CONCLUSIONS: EN provides critically-ill children with adequate energy intake and is well tolerated. Therefore, if there are no contraindications, EN should be the system of choice in the critically-ill patient requiring AN.

[Möbius syndrome and an apparently life-threatening event]. / Síndrome de Möbius y episodio aparentemente letal.

Möbius syndrome is characterized by congenital facial weakness with impairment of ocular abduction. A subgroup of these patients have associated apneas because of involvement of brainstem respiratory centers located slightly lateral to the abducens nuclei. We report a 7-month old infant admitted to the pediatric intensive care unit because of an episode of cyanosis, hypotonia and unresponsiveness. The patient then became respirator dependent afterwards. On examination, facial diplegia, impairment of ocular abduction and hypotonia were evident. Magnetic resonance imaging (MRI) revealed abnormal signal intensity in brainstem tegmentum. At the age of 11 months he was discharged but required a home ventilator. He died 5 months later due to an infection. Möbius syndrome is associated with central respiratory dysfunction. The finding of abnormal signal intensity in brainstem tegmentum on MRI is a possible predictor of apnea in these patients.

Isolation of Rickettsia massiliae from Rhipicephalus sanguineus Ticks, Buenos Aires (Argentina).

Rickettsia massiliae , a member of the spotted fever group of Rickettsia, was first isolated from a Rhipicephalus turanicus tick in France. In the New World, it has been detected in Rhipicephalus sanguineus ticks from different geographical locations in Argentina and the United States, but it has only been isolated in Arizona. The aim of this study was the isolation and genetic characterization of R. massiliae from R. sanguineus ticks collected from dogs in Buenos Aires city, Argentina. In total, 49 R. sanguineus ticks were collected from 10 dogs and grouped into 10 pools of 4-5 specimens. With a PCR assay, which detects a fragment of the Rickettsia genus-specific 23S-5S intergenic space, 1 pool of 5 ticks was found positive. Generated sequences exhibited 100% identity with R. massiliae . A new isolate, named CABA, was obtained from this pool by inoculating it into monolayers of Vero cells. Genotypic characteristics were determined, and results showed that fragments of the 23S-5S intergenic space, ompA, ompB, gltA, htrA, and sca1 genes had great similarity with R. massiliae strain Bar29 (Spain). Although few human cases have been confirmed for this pathogen, its circulation in urban areas is of great importance to public health. This isolation improves knowledge of the circulating pathogen and could improve future diagnostic processes as it allows the production of more specific antigens for serological testing.