Functional Characterization of the Cell Division Gene Cluster of the Wall-less Bacterium Mycoplasma genitalium.

It is well-established that FtsZ drives peptidoglycan synthesis at the division site in walled bacteria. However, the function and conservation of FtsZ in wall-less prokaryotes such as mycoplasmas are less clear. In the genome-reduced bacterium Mycoplasma genitalium, the cell division gene cluster is limited to four genes: mraZ, mraW, MG_223, and ftsZ. In a previous study, we demonstrated that ftsZ was dispensable for growth of M. genitalium under laboratory culture conditions. Herein, we show that the entire cell division gene cluster of M. genitalium is non-essential for growth in vitro. Our analyses indicate that loss of the mraZ gene alone is more detrimental for growth of M. genitalium than deletion of ftsZ or the entire cell division gene cluster. Transcriptional analysis revealed a marked upregulation of ftsZ in the mraZ mutant. Stable isotope labeling by amino acids in cell culture (SILAC)-based proteomics confirmed the overexpression of FtsZ in MraZ-deprived cells. Of note, we found that ftsZ expression was upregulated in non-adherent cells of M. genitalium, which arise spontaneously at relatively high rates. Single cell analysis using fluorescent markers showed that FtsZ localization varied throughout the cell cycle of M. genitalium in a coordinated manner with the chromosome and the terminal organelle (TMO). In addition, our results indicate a possible role for the RNA methyltransferase MraW in the regulation of FtsZ expression at the post-transcriptional level. Altogether, this study provides an extensive characterization of the cell division gene cluster of M. genitalium and demonstrates the existence of regulatory elements controlling FtsZ expression at the temporal and spatial level in mycoplasmas.

Dietary habits in patients with fibromyalgia: a cross-sectional study.

OBJECTIVES: To the scarce information on dietary habits in fibromyalgia (FM), it is added that there are no comparative studies with other rheumatic diseases. The objective of this study was to characterise the dietary habits of patients with FM by comparing, for the first time, with healthy controls (HC) and rheumatoid arthritis (RA). METHODS: This cross-sectional, observational study was based on data obtained from the Dietfibrom project for FM and from the IMID Consortium for RA and HC. All participants completed a food frequency questionnaire evaluating their weekly dietary intake of main food groups. The three cohorts were compared using a multiple logistic regression model adjusted for age, sex, and body mass index. RESULTS: After quality control, n=287 FM, n=1,983 HC and n=1,942 RA patients were analysed. We found that FM had a profound impact in the diet compared to HC, reducing the consumption of dairy (OR=0.32, p<0.0001), bread and/or whole grain cereals (OR=0.59, p=0.0006), fresh fruit (OR=0.66, P=0.008), and fish (OR=0.64, p=0.002). These same four food groups were also significantly reduced in FM patients in comparison to RA patients (p<0.0005 in all cases). Additionally, a lower consumption of pasta, rice and/or potatoes was also observed in FM compared to RA (OR=0.72, p=0.028). CONCLUSIONS: The present cross-sectional study shows that FM is associated to a significant change in the normal dietary patterns. These results underscore the importance of diet in this prevalent disease and are a warning of the potential long-range effects of a deficient nutritional status.

Escolar amb osteomielitis multifocal crònica recurrent / Escolar con osteomielitis multifocal cronica recurrente / Child with chronic recurrent multifocal osteomyelitis

Introducció: l'osteomielitis multifocal crònica recurrent(OMCR) és una rara entitat d'etiologia desconeguda, quesol presentar-se en la infància primerenca, caracteritzadaper afectació òssia multifocal d'evolució clínica subagudao crònica amb remissions. Es presenta com una entitat in-dependent o com una síndrome combinada amb lesions ala pell (síndrome SAPHO). Les lesions òssies imiten unaosteomielitis aguda, però els estudis microbiològics són ne-gatius. El tractament d'elecció són els antiinflamatoris noesteroïdals, encara que no hi ha un tractament específic. Cas clínic: es presenta un pacient de sexe masculí de 7anys amb dolor, pruïja i edema al segon dit de la mà dretade 13 dies d'evolució. La radiografia del dit va mostrar lesions osteolítiques a les falanges mitjana i proximal senseafectació articular. En l'analítica sanguínia destacava unaVSG augmentada. La gammagrafia òssia amb Tc-99 descrivia diverses lesions òssies amb intensa reacció osteogènicaen diferents localitzacions. La nul•la resposta al tractamentantibiòtic, la negativitat dels cultius i la biòpsia òssia inespecífica feta en més d'un focus ossi van orientar eldiagnòstic d'OMCR. S'inicià tractament amb ibuprofèn,amb millora del dolor, l'eritema i l'edema del dit fins a laresolució total. Comentaris: el diagnòstic d'OMCR es fa davant unes troballes clíniques i radiològiques compatibles, i descartant lacausa microbiològica o tumoral mitjançant l'estudi micro-biològic i histològic de la biòpsia òssia. La gammagrafia òssia és una exploració indispensable, ja que revela lesionsòssies asimptomàtiques i les que no s'aprecien amb la radiologia simple

Introducción. La osteomielitis multifocal crónica recurrente (OMCR) es una rara entidad de etiología desconocida, que suele presentarse en la infancia temprana, caracterizada por afectación ósea multifocal de evolución clínica subaguda o crónica con remisiones. Se presenta como una entidad independiente o como un síndrome combinado con lesiones en la piel (síndrome SAPHO). Las lesiones óseas imitan una osteomielitis aguda, pero los estudios microbiológicos son negativos. El tratamiento de elección son los antiinflamatorios no esteroideos, aunque no hay un tratamiento específico. Caso clínico. Se presenta un paciente de sexo masculino de 7 años con dolor, prurito y edema en segundo dedo de la mano derecha de 13 días de evolución. La radiografía del dedo mostró lesiones osteolíticas en falanges media y proximal sin afectación articular. En la analítica sanguínea destacaba una VSG aumentada. La gammagrafía ósea con Tc-99 describía varias lesiones óseas con intensa reacción osteogénica en distintas localizaciones. La nula respuesta al tratamiento antibiótico, la negatividad de los cultivos y la biopsia ósea inespecífica orientaron al diagnóstico de OMCR. Se inició tratamiento con ibuprofeno con mejoría del dolor, el eritema y el edema del dedo hasta su total resolución. Comentarios. El diagnóstico de OMCR se realiza ante unos hallazgos clínicos y radiológicos compatibles, y descartando la causa microbiológica o tumoral mediante el estudio microbiológico e histológico de la biopsia ósea. La gammagrafía ósea es una exploración indispensable, ya que revela lesiones óseas asintomáticas y aquéllas que no se aprecian con la radiología simple (AU)

Introduction. Chronic recurrent multifocal osteomyelitis (CRMO) is a rare disease of unknown etiology that usually occurs in early childhood and is characterized by multifocal bone involvement with subacute or chronic clinical course and remission periods. It comes as a separate entity or as part of a syndrome with skin lesions (SAPHO syndrome). The bone lesions mimic an acute osteomyelitis, but microbiological studies are negative. The treatment of choice is with non-steroidal anti-inflammatory drugs. Case report. We report the case of a 7-year-old male who presented with pain, itching, and swelling of the second finger of the right hand for 13 days. A plain X-ray showed osteolytic changes in the middle and proximal phalanges without joint involvement. Blood tests were significant for an elevated ESR, and Tc-99 bone scintigraphy showed multiple bone lesions with intense osteogenic response. The lack of response to antibiotics, the negative cultures, and the nonspecific findings in the multiple bone biopsies suggested the diagnosis of CRMO. Treatment with ibuprofen was started, with improvement in pain, erythema, and edema of the finger, leading to complete resolution. Comments. The diagnosis of CRMO is made based on the compatible clinical and radiological findings, once neoplastic and infectious etiologies have been ruled out by histological and microbiological examination of bone biopsy. Bone scintigraphy is the most sensitive radiological method for diagnosis, as it may reveal asymptomatic lesions and also lesions not seen on plain X-ray (AU)

Treatment of Ewing sarcoma family of tumors with a modified P6 protocol in children and adolescents.

BACKGROUND: Reported overall survival (OS) rates of patients with localized Ewing sarcoma family of tumors (ESFT) are >80% when treated with the MSKCC P6 protocol. However, it has been associated with a 5.8% incidence of secondary leukemias. A modified P6 (mP6) protocol with reduced exposure to chemotherapy is presented. PROCEDURE: Thirty-one newly diagnosed ESFT patients were enrolled onto this phase II, single-arm, non-randomized protocol. Courses 1, 2 and 4 consisted of cyclophosphamide 4.2 g/m², doxorubicin 75 mg/m², and vincristine 2 mg/m² (CDV). Cycles 3 and 5 consisted of ifosfamide 9 g/m² and etoposide 500 mg/m² (IE). Course 5 ifosfamide was 14 g/m² if necrosis was <90%. RESULTS: Twenty-four patients had loco-regional disease and seven had metastases. The 4-year event-free survival (EFS) rate for patients with localized tumors is 83% and overall survival (OS) is 92%. The 3-year EFS rate for patients with distant metastases is 28% and OS rate is 42%. EWS-FLI1 fusion genes were detected in 17 cases (74%) and EWS-ERG in six cases (26%). Type 1 EWS-FLI1 variant was present in 6/7 metastatic patients and 3/16 loco-regional cases (P = 0.001). None of the patients experienced tumor progression before remission. All relapses occurred within 2 years from the end of treatment and local relapses (n = 3) happened in patients who did not receive radiation therapy. No secondary malignancies have been observed, median follow-up of 4.3 years for surviving patients. CONCLUSIONS: In this pilot study, the mP6 protocol produced a complete remission rate of 83% at 4 years in non-metastatic ESFT reducing the risk of secondary malignancies.

Long-term results of the Spanish Protocol SO-95 for the treatment of non-metastatic high-grade osteosarcoma of the extremities in children.

INTRODUCTION: The long-term results of the Spanish Study Protocol SEOP-SO-95 for treatment of localised osteosarcoma of the extremities in children were evaluated. PATIENTS AND METHODS: One hundred consecutive patients under 18 years of age from 22 institutions were enrolled from January 1995 to December 2000. Immunohistochemical expression of p53, HER/erbB-2 and P-glycoprotein were retrospectively studied in 27 patients. Treatment consisted of: preoperative chemotherapy with doxorubicin, cisplatin, high-dose methotrexate with leucovorin rescue and ifosfamide for 14 weeks; surgery of primary tumour in week 16; postoperative chemotherapy with the above-mentioned drugs for 25 weeks. RESULTS: With a median follow-up of 124 months (range 84-158 months), 69 patients (69%) were continuously event-free survivors; the 10-year probability of event-free survival (EFS) was 62%. Conservative surgery was performed in 85% of patients. Twenty-six patients had local recurrence or distant relapse. The median time to recurrence/ relapse was 27 months (range 17-93 months). The local recurrence rate was 7% (7 of the 100 patients); 4 had wide surgical margins, 2 marginal and 1 intralesional. Four patients died as a result of chemotherapy-related toxicity and 1 developed a second neoplasia (acute myeloid leukaemia). p53 expression and HER2/erbB-2 expression showed no effect on survival or EFS. CONCLUSIONS: This therapeutic protocol achieved good oncologic and orthopaedic results. We observed a significant treatment-related toxicity.

Incidence study of nosocomial infection in pediatric trauma patients.

In this article we intend to describe the epidemiological profile of nosocomial infection in pediatric patients with multiple trauma. We conducted a prospective study from July to November 2003 in a pediatric teaching hospital in Barcelona. We used US Centers for Disease Control and Prevention standard criteria to define nosocomial infection. Of the 121 patients included in the study, 33% had at least one episode of nosocomial infection, with an incidence rate of 9.9 infections per 100 admissions and 1.1 infections per 100 patient-days. The most frequent episode of nosocomial infection was bacteremia. Coagulase-negative staphylococci were the most common pathogens. Nosocomial infection rates per 100 device-days were 3.2 for bacteremia, 1.6 for respiratory infection and 1.0 for urinary tract infection. These findings suggest the need to evaluate infection control measures aimed at reducing the morbidity associated with infections.

Enhanced culture detection of Kingella kingae, a pathogen of increasing clinical importance in pediatrics.

Osteoarticular infection and occult bacteremia are the 2 invasive infectious pathologies most frequently associated in childhood with Kingella kingae. We report a series of 11 patients in whom osteomyelitis predominates over septic arthritis, which is the reverse of other series, probably as a consequence of inoculation of samples during surgery on agar media, used in combination with or as an alternative to inoculation into blood culture bottles. Although K. kingae infections usually follow a benign clinical course, we noted 2 patients with mild orthopedic sequelae.