Maxillary sinus angiolymphoid hyperplasia with eosinophilia associated to orbital and cutaneous lesion.

INTRODUCTION: We describe the first case of ALHE in the orbit with extension to the maxillary sinus and the importance of a multidisciplinary approach to achieve removal of the lesion. CASE STUDY: A 72-year-old man presented with epiphora of the left eye and several episodes of recurrent acute dacryocystitis. Magnetic resonance imaging revealed a solid homogeneous mass located in the inferomedial region of the left orbit. In addition, it was associated with destruction of the adjacent ethmoidal wall and upper wall of the left maxillary sinus. Incisional biopsy of the orbital mass was compatible with ALHE. RESULTS: It was decided to perform surgery using an orbital floor approach, left medial wall via subconjunctival and caruncular approach together with an endoscopic nasal approach (ESS), achieving complete removal of the orbital mass and cleaning of the maxillary sinus. After one year of treatment, no tumor recurrence was evident through endoscopy and imaging tests and the patient is asymptomatic. CONCLUSIONS: ALHE is a very rare benign vascular tumor that presents subcutaneous nodules in the head and neck region. We do not know of any case of ALHE in the paranasal sinuses described in the literature, either in isolation or together with orbital or cutaneous ALHE. In conclusion, ALHE disease should be considered as a diagnosis when faced with an orbital mass with extension to the paranasal sinuses, and a complete excision through a combined endonasal and orbital approach prevents recurrence in most cases.

Fluctuating facial edema as a rare manifestation of cutaneous polyarteritis nodosa: Case report and review of the literature.

Polyarteritis nodosa (PAN) is a necrotizing vasculitis. The clinical manifestations are determined by the location of the compromised arteries. Cutaneous PAN can present as nodular lesions similar to erythema nodosum, palpable purpura, livedo reticularis, and ulceration. It often affects the lower limbs but other anatomical sites can also be involved. However, concomitant facial edema is an extremely rare manifestation. It has been more than 20 years since the last case report describing this unusual presentation of PAN. Furthermore, our patient is the first case presenting with hemifacial edema fluctuating every second or third day due to PAN confirmed by skin biopsy.

Long COVID Symptoms in Non-Hospitalised Patients: A Retrospective Study.

INTRODUCTION: The COVID-19 pandemic has presented numerous challenges to healthcare systems. As the number of affected individuals continues to rise, it is crucial to find preventive, diagnostic, and therapeutic approaches. This study aims to describe different COVID-19 sequelae within a Primary Health Care population. METHODS: A retrospective cohort study was conducted in adults diagnosed with COVID-19 from March 2020 to April 2022, excluding pregnant women, minors, nursing home residents, hospitalizations, and deaths. Data was gathered from surveillance records on the Trace COVID-19® platform, a pre-set original questionnaire (which included the Portuguese version of the World Health Organization's Quality of Life Assessment Instrument), and, if needed, patient electronic health records. Information on sociodemographic and clinical characteristics of acute COVID-19 was collected along with long COVID symptoms. RESULTS: This study included 284 patients, aged 19 to 99 years old. The five most prevalent acute COVID-19 symptoms were fever (50.0%), tiredness (48.2%), myalgias (44.7%), dry cough (37.7%) and odynophagia (36.3%). Symptoms related to the neurological system (23.2%) and tiredness (22.9%) were the most prevalent in long COVID symptoms. Acute tiredness and arthralgia were associated with all long COVID outcomes. The associations between acute COVID-19 symptoms with long COVID outcomes were stronger for anosmia [OR = 5.07, 95% confidence interval (CI) 2.49 - 10.36, p < 0.001] on a neurological chapter, acute tiredness for long lasting tiredness (OR = 4.07, 95% CI 2.07 - 8.02, p = 0.041), fatigue for muscles and/or bones chapter (OR = 7.55, 95% CI 3.06 - 18.66, p < 0.001), tiredness on an endocrine/hormonal chapter (OR = 6.54, 95% CI 2.37 - 18.04, p < 0.001), dyspnea for respiratory symptoms (OR = 5.67, 95% CI 1.92 - 16.74, p = 0.002) and fever for stomach or intestine symptoms (OR = 8.06, 95% CI 2.55 - 25.47, p < 0.001). Almost all quality of life dimensions were negatively associated with the number of long COVID symptoms. CONCLUSION: A higher number of acute symptoms, as well as the presence of specific COVID-19 symptoms were associated with reported symptoms ≥ 12 weeks after infection. In the studied population, an increased number of symptoms in both acute and long COVID had a significant negative impact on the perception of overall quality of life. The identification of these relationships could provide a new perspective for post-COVID care.

Recurrent and recalcitrant upper lid cicatricial entropion following combined chemotherapy: Clinical and pathology correlation.

We report a case of recalcitrant bilateral upper eyelid cicatricial entropion associated with distichiasis/trichiasis which followed an adjuvant systemic chemotherapy. The chemotherapy, administered for treatment of breast cancer, consisted of docetaxel, carboplatin, and herceptin. Shortly following the combined chemotherapy treatment, epiphora and eyelash abnormalities commenced. The patient presented with a swollen eyelid margin and tarsal conjunctival inflammation associated with cicatricial entropion and diffused distichiasis/trichiasis affecting the upper lids, with greater severity observed in the medial portion. Despite manual epilation and multiple argon laser sessions, no improvement was noted. Surgical treatment was performed using a lid split, distichiasis excision of the right upper lid, and homolateral tarsoconjunctival graft. The biopsy examination showed chronic inflammation, dermal fibrosis with squamous metaplasia process, and an abnormal epithelial differentiation. After 6 months, entropion recurred. Tarsal marginal rotation associated with posterior lamella advancement was performed. However, cicatricial entropion and distichiasis/trichiasis recurred. The patient was prescribed bandage contact lenses and topical lubrication to relieve symptoms.

Concurrent xanthogranulomatous orchiepididymitis and seminoma in the same testis.

Xanthogranulomatous orchiepididymitis (XGO) is a rare inflammatory and destructive disease of the testis that may simulate testicular malignancy. To the authors' knowledge only 19 cases of XGO have been previously reported. Herein is reported the case of a 52-year-old man with XGO who presented with a left testicular mass and pyogenic discharge from the scrotum. Ultrasound examination indicated heterogeneous testicular areas suggestive of neoplasia. Testicular tumor markers were normal. Orchidectomy was performed and histopathology showed XGO and a concurrent, occult typical seminoma. As far as the authors know the coincidence of these two lesions has not been documented previously. XGO may mimic testicular malignancy and may coexist with it. Pathologists should be aware of this concurrence of lesions to avoid potential misdiagnosis. Wide sampling of the orchidectomy specimens with XGO is mandatory to exclude an occult seminoma.

Solitary fibrofolliculoma: a retrospective case series review over 18 years.

PURPOSE: The purpose of this study was to report a series of cases of solitary fibrofolliculoma, a lesion seldom observed in the lids. Demographics, as well as clinical and histological aspects of the lesion were evaluated. METHODS: This was a retrospective case series spanning a period of 18 years. All the included patients were diagnosed with solitary fibrofolliculoma confirmed by histological examination. Data regarding patient demographics, signs, and symptoms, course of the disease, location of the lesion, clinical and histological diagnosis, and outcome were collected. RESULTS: Eleven cases of solitary fibrofolliculoma were diagnosed in the study period. The median age of patients was 51 ± 16.3 years (range: 27-78 years). Most patients were females (7/11; 64%). Five of the patients (45%) were asymptomatic; four (36%) reported bleeding, one (9%) had referred itching, and one (9%) rubbing of the lesion. The lesion occurred in a wide range of locations; one of them was located in the lids. The diagnosis for all lesions was histological based on characteristic findings of a hair follicle occasionally dilated and containing keratin material surrounded by a moderately well-circumscribed thick mantle of fibrous tissue. The infundibular follicular epithelium extended out into this fibrous mantle forming epithelial strands or cords. There were no relapses after exeresis. CONCLUSION: Solitary fibrofolliculoma is a rare lesion, seldom affecting the eyelids. We reported 11 cases, and the third case reported thus far in the literature affecting the lids. Diagnosis may be easily missed due to the nonspecific symptoms and clinical appearance. Therefore, it is necessary to perform excisional biopsy and histological examination for the recognition of this lesion.

Hemangioma fusocelular. Presentación de un caso y revisión de la literatura

El hemangioma fusocelular es un tumor vascular benigno poco frecuente. Se ha relacionado con el síndrome de Maffucci, el síndrome de Klippel-Trenaunay y otras malformaciones venosas. Habitualmente son nódulos dérmicos de color violáceo en las extremidades distales de niños y adultos jóvenes, sin predilección por ningún sexo. Se presenta el caso de una paciente de 22 años que padecía un nódulo subcutáneo, doloroso a la presión, en la pierna derecha. A la exploración física se observó una tumoración redondeada violácea de 1,5 cm. Se sospechó la presencia de un hemangioma. Se realizó una escisión simple y se envió al departamento de anatomía patológica. Se describió la muestra como nódulo intraluminal constituido por una proliferación de células de aspecto fusiforme con moderada atipia y aisladas figuras de mitosis y se confirmó el diagnóstico de hemangioma fusocelular de localización intravascular. El diagnóstico del hemangioma fusocelular es anatomopatológico y como tratamiento suele bastar la escisión simple, aunque frecuentemente recidivan. Dado que el hemangioma fusocelular es una entidad poco conocida y puede ser confundida con otras lesiones vasculares, se considera interesante la comunicación del presente caso. El conocimiento de este tipo de lesión puede aumentar los casos notificados.

Spindle cell hemangioma is a rare benign vascular tumor. It has been linked to Maffucci syndrome, Klippel-Trenaunay syndrome, and other venous malformations. They are usually purplish dermal nodules on the distal extremities of children and young adults, with no sex predilection. A case of a 22-years-old patient who suffered from a subcutaneous nodule, painful on pressure, in the right leg is presented. On physical examination, a 1.5 cm violaceous round tumor was observed. The presence of a hemangioma was suspected. A simple excision was performed and sent to the pathology department. The sample was described as an intraluminal nodule made up of a proliferation of spindle-shaped cells with moderate atypia and isolated mitotic figures, and the diagnosis of intravascular spindle cell hemangioma was confirmed. The diagnosis of spindle cell hemangioma is anatomopathological and simple excision is usually sufficient as treatment, although they frequently recur. Since spindle cell hemangioma is a little-known entity and can be confused with other vascular lesions, the communication of this case is considered interesting. Knowledge of this type of injury can increase reported cases.

Antibody persistence and booster responses 24-36 months after different 4CMenB vaccination schedules in infants and children: A randomised trial.

OBJECTIVES: This phase IIIb, open-label, multicentre, extension study (NCT01894919) evaluated long-term antibody persistence and booster responses in participants who received a reduced 2 + 1 or licensed 3 + 1 meningococcal serogroup B vaccine (4CMenB)-schedule (infants), or 2-dose catch-up schedule (2-10-year-olds) in parent study NCT01339923. MATERIALS AND METHODS: Children aged 35 months to 12 years (N = 851) were enrolled. Follow-on participants (N = 646) were randomised 2:1 to vaccination and non-vaccination subsets; vaccination subsets received an additional 4CMenB dose. Newly enrolled vaccine-naïve participants (N = 205) received 2 catch-up doses, 1 month apart (accelerated schedule). Antibody levels were determined using human serum bactericidal assay (hSBA) against MenB indicator strains for fHbp, NadA, PorA and NHBA. Safety was also evaluated. RESULTS: Antibody levels declined across follow-on groups at 24-36 months versus 1 month post-vaccination. Antibody persistence and booster responses were similar between infants receiving the reduced or licensed 4CMenB-schedule. An additional dose in follow-on participants induced higher hSBA titres than a first dose in vaccine-naïve children. Two catch-up doses in vaccine-naïve participants induced robust antibody responses. No safety concerns were identified. CONCLUSION: Antibody persistence, booster responses, and safety profiles were similar with either 2 + 1 or 3 + 1 vaccination schedules. The accelerated schedule in vaccine-naïve children induced robust antibody responses.

Reduced schedules of 4CMenB vaccine in infants and catch-up series in children: Immunogenicity and safety results from a randomised open-label phase 3b trial.

BACKGROUND: This study evaluated the immunogenicity and safety of a licensed meningococcal serogroup B vaccine (4CMenB) administered alone according to reduced schedules in infants or catch-up series in children. METHODS: In this open-label, multicentre, phase 3b study (NCT01339923), infants randomised 1:1:1 received 4CMenB: 2+1 doses at 3½-5-11months or 6-8-11months of age, 3+1 doses at ages 2½-3½-5-11months. Children aged 2-10years received 2 catch-up doses administered 2months apart. Immune responses were measured by hSBA assays against 4 strains specific for vaccine components fHbp, NadA, PorA and NHBA. Sufficiency of immune responses was defined in groups with 2+1 doses schedules as a lower limit ≥70% for the 97.5% confidence interval of the percentage of infants with hSBA titres ≥4, 1month post-dose 2 for fHbp, NadA, PorA. Adverse events were collected for 7days post-vaccination; serious adverse events (SAEs) throughout the study. RESULTS: 754 infants and 404 children were enrolled. Post-primary vaccination, 98-100% of infants across all groups developed hSBA titres ≥4 for fHbp, NadA, PorA, and 48-77% for NHBA. Sufficiency of immune responses in infants receiving 2+1 schedules was demonstrated for fHbp, NadA, PorA after 2 doses of 4CMenB, as pre-specified criteria were met. Following receipt of 2 catch-up doses, 95-99% of children developed hSBA titres ≥4 for 4CMenB components. Similar safety profiles were observed across groups. A total of 45 SAEs were reported, 3 of which were related to vaccination. CONCLUSION: Reduced infant schedules and catch-up series in children were immunogenic and safe, having the potential to widen 4CMenB vaccine coverage. FUNDING: GlaxoSmithKline Biologicals SA.

Excess hospitalizations, hospital days, and inpatient costs among people with diabetes in Andalusia, Spain.

OBJECTIVE: The goal of this study was to estimate the excess hospitalizations, hospital days, and inpatient costs attributable to diabetes in Andalusia, Spain (37 hospitals, 7,236,459 inhabitants), during 1999 compared with those without diabetes. RESEARCH DESIGN AND METHODS: This study was an analysis of all hospital discharges. Those with an ICD-9-CM code of 250 as either the main or secondary diagnosis were considered to have been admissions of individuals with diabetes. An estimate of costs was applied to each inpatient admission by assigning a cost weight based on the diagnostic-related group (DRG) related to each admission. RESULTS: A total of 538,580 admissions generated 4,310,654 hospital bed-days and total costs of 940,026,949 euro. People with diabetes accounted for 9.7% of all hospital discharges, 13.8% of total stays, and 14.1% of the total cost. Of the total cost for individuals with diabetes (132,509,217 euro), 58.3% were excess costs, of which 47% was attributable to cardiovascular complications and 43% to admissions for comorbid diseases. Individuals 45-75 years of age accounted for 75% of the excess costs. The rate of admissions during the study year was 145 per 1,000 inhabitants for individuals with diabetes compared with 70 admissions per 1,000 inhabitants for individuals without diabetes. CONCLUSIONS: The costs arising from hospitalization of individuals with diabetes are disproportionate in relation to their prevalence. For those aged >or=45 years, cardiovascular complications were clearly the most important factor determining increased costs from diabetes.

Solitary fibrofolliculoma: a retrospective case series review over 18 years / Fibrofoliculoma solitário: revisão de série retrospectiva de casos de 18 anos

ABSTRACT Purpose: The purpose of this study was to report a series of cases of solitary fibrofolliculoma, a lesion seldom observed in the lids. Demographics, as well as clinical and histological aspects of the lesion were evaluated. Methods: This was a retrospective case series spanning a period of 18 years. All the included patients were diagnosed with solitary fibrofolliculoma confirmed by histological examination. Data regarding patient demographics, signs, and symptoms, course of the disease, location of the lesion, clinical and histological diagnosis, and outcome were collected. Results: Eleven cases of solitary fibrofolliculoma were diagnosed in the study period. The median age of patients was 51 ± 16.3 years (range: 27-78 years). Most patients were females (7/11; 64%). Five of the patients (45%) were asymptomatic; four (36%) reported bleeding, one (9%) had referred itching, and one (9%) rubbing of the lesion. The lesion occurred in a wide range of locations; one of them was located in the lids. The diagnosis for all lesions was histological based on characteristic findings of a hair follicle occasionally dilated and containing keratin material surrounded by a moderately well-circumscribed thick mantle of fibrous tissue. The infundibular follicular epithelium extended out into this fibrous mantle forming epithelial strands or cords. There were no relapses after exeresis. Conclusion: Solitary fibrofolliculoma is a rare lesion, seldom affecting the eyelids. We reported 11 cases, and the third case reported thus far in the literature affecting the lids. Diagnosis may be easily missed due to the nonspecific symptoms and clinical appearance. Therefore, it is necessary to perform excisional biopsy and histological examination for the recognition of this lesion.

RESUMO Objetivo: o objetivo deste estudo foi relatar uma série de casos de fibrofoliculoma solitário, uma lesão raramente observada nas pálpebras. Demografia, bem como aspectos clínicos e histológicos da lesão foram avaliados. Métodos: Trata-se de uma série de casos retrospectivos, com um período de 18 anos. Todos os pacientes incluídos foram diagnosticados com fibrofoliculoma solitário confirmado por exame histológico. Foram coletados dados referentes à demografia, sinais e sintomas dos pacientes, evolução da doença, localização da lesão, diagnóstico clínico e histológico e desfecho. Resultados: Onze casos de fibrofoliculoma solitário foram diagnosticados no período do estudo. A média de idade dos pacientes de 51 ± 16,3 anos (variação: 27-78 anos). A maioria dos pacientes era do sexo feminino (7/11, 64%). Cinco dos pacientes (45%) eram assintomáticos; quatro (36%) relataram sangramento, um (9%) referiu coceira e um (9%) fricção da lesão. A lesão ocorreu em luma ampla variedade de locais; um deles sendo nas pálpebras. O diagnóstico de todas as lesões foi histológico com base nos achados característicos de um folículo piloso ocasionalmente dilatado e contendo material de queratina, cercado por um manto espesso de tecido fibroso moderadamente bem circunscrito. O epitélio infundibular folicular se estendeu até esse manto fibroso, formando cordões ou cordões epiteliais. Não houve recaídas após exérese. Conclusão: Fibrofoliculoma solitário é uma lesão rara, mais ainda quando afeta as pálpebras. Relatamos 11 casos, e o terceiro relatado até o momento na literatura que afeta as pálpebras. O diagnóstico pode ser facilmente esquecido devido a sintomas inespecíficos e aparência clínica. Portanto, é necessário realizar biópsia excisional e exame histológico para o reconhecimento dessa lesão.

Asociación del peso al nacer con adiposidad en niños escolares de distintas regiones de argentina / Association of birth weight with adiposity in school children from different regions of argentina

Introducción: diversos estudios han sugerido que el bajo y alto peso al nacer (PN) se asocian a obesidad (OB) y sobrepeso (SP) durante la infancia y la edad adulta. Objetivos: determinar la asociación entre PN y OB en escolares de 9 años de tres regiones de Argentina. Materiales y métodos: las medidas antropométricas y la presión arterial (PA) se tomaron en 1.131 escolares (505 masculinos) de 8,8±2,1 años de edad promedio, en tres regiones de Argentina durante el año 2019. Se interrogó, además, acerca del peso al nacer y el estilo de vida. Resultados: el 21,1% (239) de los niños presentaba SP (IMC>85 <95 percentilo según CDC) y el 21,8% (246) OB (IMC>95 percentilo). La prevalencia de PN bajo (<2.500 g) fue de fue de 6,2% (n=70) y de PN alto (>4.000 g) de 7,3% (n=82). El puntaje z-IMC de los niños de 9 años aumentaba significativamente con el aumento del PN: PN bajo (z-IMC=0,33), normal (z-IMC=0,72) y alto (z-IMC=1,12). En modelos de regresión logística múltiple se observó que el PN bajo se asoció inversamente a la OB (OR, 0.41 [IC del 95%: 0,19-0,92]), mientras que el PN alto se asoció directamente con la OB ajustado por edad y sexo (OR, 2.48 [95% IC 1,53-4,02]). Conclusiones: nuestros datos indican que el alto PN, pero no el bajo PN, se asocia con OB en niños en edad escolar de 9 años, mientras que el bajo PN está inversamente asociado con OB.

Introduction: several studies have suggested that low and high birth weight are associated with obesity (OB) and overweight (OW) during childhood and adulthood. Objectives: to determine the association between birth weight and OB in 9-year-old schoolchildren from three areas of Argentina. Materials and methods: anthropometric measurements and blood pressure (BP) were taken in 1.131 schoolchildren (505 males) of an average age of 8.8±2.1 years in three areas of Argentina during 2019. Mothers were asked about their children's birth weight and lifestyle. Results: 21.1% (239) of the children had OW (BMI>85 <95 percentile according to the CDC) and 21.8% (246) OB (BMI>95 percentile). The prevalence of low birth weight (<2.500 g) was 6.2% (n=70) and of high birth weight (>4.000 g) was 7.3% (n=82). The 9-year-old z-BMI score increased significantly with increasing birth weight: low birth weight (z-BMI=0.33), normal (z-BMI=0.72) and high (z-BMI=1.12). In multiple logistic regression models, it was found that low birth weight was inversely associated with OB (OR, 0.41 [95% CI: 0.19-0.92]), while high birth weight was directly associated with OB adjusted for age and sex (OR, 2.48 [95% CI 1.53-4.02]). Conclusions: our data indicate that high birth weight, but not low birth weight, is associated with OB in 9-year-old schoolchildren, while low birth weight is inversely associated with OB

Evaluation of 13-valent pneumococcal conjugate vaccine and concomitant meningococcal group C conjugate vaccine in healthy infants and toddlers in Spain.

BACKGROUND: Given the concurrent administration of multiple vaccines during routine pediatric immunizations, efforts to elucidate the potential interference of any vaccine on the immune response to the concomitantly administered antigens are fundamental to prelicensure clinical research. METHODS: This phase 3 randomized controlled trial of 13-valent pneumococcal conjugate vaccine (PCV13) versus 7-valent PCV (PCV7) assessed immune responses of concomitantly administered meningococcal group C conjugated to diphtheria toxin cross-reactive material 197 (MnCCV-CRM197) in a 2-dose infant series and 15-month toddler dose. RESULTS: 619 subjects were randomized, 315 to PCV13 and 304 to PCV7. MnCCV-CRM197-induced immune responses were similar between the PCV13 and PCV7 groups, with >97% of the subjects achieving a ≥1:8 meningococcal serum bactericidal assay (SBA) titer after both dose 2 and the toddler dose. Geometric mean titers were lower in the PCV13 group 191.22 (167.72, 218.02) versus 266.19 (234.86, 301.71) following dose 2 and 432.28 (361.22, 517.31) versus 730.84 (642.05, 831.91) following the toddler dose. The geometric mean (GM) meningococcal SBA titer ratios (PCV13/PCV7) were 0.72 after dose 2 and 0.59 after the toddler dose. The criteria for MnCCV-CRM197 non-inferiority for GM titers were satisfied after dose 2. Percent responders was similar up to titers of 1:128. PCV13 elicited substantial antipneumococcal responses against all 13 serotypes, with ≥90% of the subjects achieving an antibody concentration ≥0.35µg/mL after dose 3 in the infant series. Safety and tolerability were similar between the vaccine groups. CONCLUSIONS: Immunogenicity results of MnCCV-CRM197 for PCV13 compared with PCV7 included lower GMTs, but the clinical significance of this is unknown as the proportion of infants achieving protective MenC antibody titers was comparable in the two groups. Percent responders were similar up to titers of 1:128. PCV13 has an acceptable safety profile in infants and toddlers, while providing expanded coverage against pneumococcal disease.

Micronuclei induced by imipramine and desipramine in mice: a subchronic study.

Depression is a common disease that may cause severe damage to human health. Imipramine (IMI) and desipramine (DES) are medicaments used for treatment, yet studies on their genotoxic potential have given controversial results. Therefore, we designed the present assay to determine their effect as inducers of micronucleated polychromatic erythrocytes (MNPE) and micronucleated normochromatic erythrocytes (MNNE) in mice. The study was carried out in animals administered daily with the compounds for 4 weeks, and the determination of micronuclei was done each week. We also evaluated the bone marrow cytotoxicity induced by the chemicals. Besides, the same determinations were carried out in the following 4 consecutive weeks, but in this period the animals were not treated with the tested compounds. Our results showed a significant increase in both MNPE and MNNE induced by both compounds from the first week of administration. At the fourth week, IMI increased three times the control level, while the effect of DES was about seven times such level. In the second, 4-week phase, we observed a reduction in the rate of micronuclei approaching the control level. We also detected a bone marrow-mitotic division decrease by the evaluated chemicals. Our results point to the need for cautiousness in the clinical use of the compounds as well as for testing the effect in patients under treatment.

Characterization of interactions between the transcriptional repressor PhlF and its binding site at the phlA promoter in Pseudomonas fluorescens F113.

The phlACBD genes responsible for the biosynthesis of the antifungal metabolite 2,4-diacetylphloroglucinol (PHL) by the biocontrol strain Pseudomonas fluorescens F113 are regulated at the transcriptional level by the pathway-specific repressor PhlF. Strong evidence suggests that this regulation occurs mainly in the early logarithmic phase of growth. First, the expression of the phlF gene is relatively high between 3 and 13 h of growth and relatively low thereafter, with the phlACBD operon following an opposite expression profile. Second, the kinetics of PHL biosynthesis are specifically altered in the logarithmic phase in a P. fluorescens F113 phlF mutant. The phlA-phlF intergenic region presents a complex organization in that phlACBD is transcribed from a sigma(70) RNA polymerase-dependent promoter that is likely to overlap the promoter of the divergently transcribed phlF gene. The repression by PhlF is due to its interaction with an inverted repeated sequence, phO, located downstream of the phlA transcriptional start site. Cross-linking experiments indicate that PhlF can dimerize in solution, and thus PhlF may bind phO as a dimer or higher-order complex. Furthermore, it is now demonstrated that certain regulators of PHL synthesis act by modulating PhlF binding to phO. PHL, which has previously been shown to be an autoinducer of PHL biosynthesis, interacts with PhlF to destabilize the PhlF-phO complex. Conversely, the PhlF-phO complex is stabilized by the presence of salicylate, which has been shown to be an inhibitor of phlA expression.