Novel BRD2::NUTM1 Fusion in NUT Carcinoma With Exceptional Response to Chemotherapy: A Case Report.

We present the first known case of a patient with BRD2::NUTM1-driven NUT carcinoma. A 59-year-old woman presented with poorly differentiated squamous cell lung cancer metastatic to the pleura. Eventually, a positive NUT immunohistochemistry, NUT fluorescence in situ hybridization, and RNA next-generation sequencing with a BRD2::NUTM1 fusion led to the diagnosis of NUT carcinoma. She received multiple lines of chemotherapy with response and is still alive at 2 years postdiagnosis. This report expands on the known fusions in NUT carcinoma and highlights potential differences in patient prognosis on the basis of gene fusion partners.

Resistance to deltamethrin, fipronil and ivermectin in the brown dog tick, Rhipicephalus sanguineus sensu stricto, Latreille (Acari: Ixodidae).

Rhipicephalus sanguineus sensu stricto (s.s.), the temperate lineage of the brown dog tick, is the most common tick found on dogs from urban areas in Rio Grande do Sul (RS) state, southern Brazil. Chemical treatments against ticks are important to control this pest, but can lead to selection for acaricide resistance. Unfortunately, little is known about acaricide resistance in this tick species in Brazil, although such information is very important to companion animal clinical practice. The objective of this study was to analyze acaricide susceptibility of R. sanguineus s.s. from the metropolitan area of Porto Alegre, RS. Engorged females ticks were collected in ten different locations, from naturally infested dogs or the environment (homes, shelters and kennels). The progenies were used in toxicological larval tests with deltamethrin, fipronil and ivermectin. Mortality data was used to determine the median lethal concentrations (LC50) for each tick population and resistance was characterized based on relative susceptibility of the different tick populations against each acaricide. Seven samples were considered resistant to deltamethrin, with resistance ratios (RR) ranging from 2.32 to 5.67. From five tick populations tested with fipronil, three were considered resistant, with RR varying from 2.56 to 13.83. For ivermectin, resistance ratios were lower, ranging from 1.54 to 2.97. The results reveal a notable variance of susceptibility to deltamethrin, fipronil and ivermectin in the R. sanguineus s.s. populations studied. This study documents for the first time the existence of acaricide-resistant populations of R. sanguineus s.s. in Brazil.

Proteomic identification of the heterogeneous nuclear ribonucleoprotein K as irradiation responsive protein related to migration.

Irradiation resistance is a major obstacle of head and neck squamous cell carcinoma (HNSCC) therapy, limiting treatment success and patient survival. The aim of our experiments was to identify irradiation-regulated proteins as potential drug targets. Two established HNSCC cell lines (HNSCCUM-01T and HNSCCUM-02T) were treated with a single 8Gy (Gray) fraction of irradiation. Changes in cellular protein expression were studied after 24h by means of 2D-electrophoresis and MALDI-TOF-mass spectrometry. Ninety-four differentially expressed proteins were identified. The expression levels of four proteins were regulated similarly in both cell lines after irradiation treatment, i.e., GRP78, PRDX, ACTC, and the heterogeneous nuclear ribonucleoprotein K (hnRNPK), suggesting a relevant role during irradiation response. hnRNPK as a p53 interacting protein was verified by Western blotting and immunocytochemical staining as well as functionally analyzed. Knock-down by the use of siRNA resulted in only slightly reduced viability, however, migratory activity was strongly reduced. Combined application of siRNA against hnRNPK and irradiation reduced migration almost completely. We conclude that hnRNPK is potentially implicated in the radiogenic response of HNSCC. The inhibition of hnRNPK might reduce the metastasizing potential of HNSCC especially in combination with irradiation and suggest that this molecule should be further evaluated in this context. BIOLOGICAL SIGNIFICANCE: We showed completely impaired migration of irradiated hnRNPK-knock-out HNSCC cells, suggesting this molecule as a potential drug target in combined treatment schedules.

Transglutaminase 2: a new player in bronchopulmonary dysplasia?

Aberrant remodelling of the extracellular matrix in the developing lung may underlie arrested alveolarisation associated with bronchopulmonary dysplasia (BPD). Transglutaminases are regulators of extracellular matrix remodelling. Therefore, the expression and activity of transglutaminases were assessed in lungs from human neonates with BPD and in a rodent model of BPD. Transglutaminase expression and localisation were assessed by RT-PCR, immunoblotting, activity assay and immunohistochemical analyses of human and mouse lung tissues. Transglutaminase regulation by transforming growth factor (TGF)-ß was investigated in lung cells by luciferase-based reporter assay and RT-PCR. TGF-ß signalling was neutralised in vivo in an animal model of BPD, to determine whether TGF-ß mediated the hyperoxia-induced changes in transglutaminase expression. Transglutaminase 2 expression was upregulated in the lungs of preterm infants with BPD and in the lungs of hyperoxia-exposed mouse pups, where lung development was arrested. Transglutaminase 2 localised to the developing alveolar septa. TGF-ß was identified as a regulator of transglutaminase 2 expression in human and mouse lung epithelial cells. In vivo neutralisation of TGF-ß signalling partially restored normal lung structure and normalised lung transglutaminase 2 mRNA expression. Our data point to a role for perturbed transglutaminase 2 activity in the arrested alveolarisation associated with BPD.

Glucocorticoids recruit Tgfbr3 and Smad1 to shift transforming growth factor-ß signaling from the Tgfbr1/Smad2/3 axis to the Acvrl1/Smad1 axis in lung fibroblasts.

Glucocorticoids represent the mainstay therapy for many lung diseases, providing outstanding management of asthma but performing surprisingly poorly in patients with acute respiratory distress syndrome, chronic obstructive pulmonary disease, lung fibrosis, and blunted lung development associated with bronchopulmonary dysplasia in preterm infants. TGF-ß is a pathogenic mediator of all four of these diseases, prompting us to explore glucocorticoid/TGF-ß signaling cross-talk. Glucocorticoids, including dexamethasone, methylprednisolone, budesonide, and fluticasone, potentiated TGF-ß signaling by the Acvrl1/Smad1/5/8 signaling axis and blunted signaling by the Tgfbr1/Smad2/3 axis in NIH/3T3 cells, as well as primary lung fibroblasts, smooth muscle cells, and endothelial cells. Dexamethasone drove expression of the accessory type III TGF-ß receptor Tgfbr3, also called betaglycan. Tgfbr3 was demonstrated to be a "switch" that blunted Tgfbr1/Smad2/3 and potentiated Acvrl1/Smad1 signaling in lung fibroblasts. The Acvrl1/Smad1 axis, which was stimulated by dexamethasone, was active in lung fibroblasts and antagonized Tgfbr1/Smad2/3 signaling. Dexamethasone acted synergistically with TGF-ß to drive differentiation of primary lung fibroblasts to myofibroblasts, revealed by acquisition of smooth muscle actin and smooth muscle myosin, which are exclusively Smad1-dependent processes in fibroblasts. Administration of dexamethasone to live mice recapitulated these observations and revealed a lung-specific impact of dexamethasone on lung Tgfbr3 expression and phospho-Smad1 levels in vivo. These data point to an interesting and hitherto unknown impact of glucocorticoids on TGF-ß signaling in lung fibroblasts and other constituent cell types of the lung that may be relevant to lung physiology, as well as lung pathophysiology, in terms of drug/disease interactions.

Deregulation of the lysyl hydroxylase matrix cross-linking system in experimental and clinical bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a common and serious complication of premature birth, characterized by a pronounced arrest of alveolar development. The underlying pathophysiological mechanisms are poorly understood although perturbations to the maturation and remodeling of the extracellular matrix (ECM) are emerging as candidate disease pathomechanisms. In this study, the expression and regulation of three members of the lysyl hydroxylase family of ECM remodeling enzymes (Plod1, Plod2, and Plod3) in clinical BPD, as well as in an experimental animal model of BPD, were addressed. All three enzymes were localized to the septal walls in developing mouse lungs, with Plod1 also expressed in the vessel walls of the developing lung and Plod3 expressed uniquely at the base of developing septa. The expression of plod1, plod2, and plod3 was upregulated in the lungs of mouse pups exposed to 85% O2, an experimental animal model of BPD. Transforming growth factor (TGF)-ß increased plod2 mRNA levels and activated the plod2 promoter in vitro in lung epithelial cells and in lung fibroblasts. Using in vivo neutralization of TGF-ß signaling in the experimental animal model of BPD, TGF-ß was identified as the regulator of aberrant plod2 expression. PLOD2 mRNA expression was also elevated in human neonates who died with BPD or at risk for BPD, compared with neonates matched for gestational age at birth or chronological age at death. These data point to potential roles for lysyl hydroxylases in normal lung development, as well as in perturbed late lung development associated with BPD.

Associations between adult attachment characteristics, medical burden, and life satisfaction among older primary care patients.

We investigated whether attachment security, measured by the Adult Attachment Prototype Rating (AAPR), was correlated with life satisfaction, independent of sociodemographic characteristics, medical burden, and age-related coping strategies in a sample of 81 patients (69-73 years) recruited from the register of a general primary care practice. Furthermore, we examined whether patients classified as AAPR-secure reported better adjustment to medical burden in terms of higher life satisfaction than did insecure patients. Attachment security was independently related to life satisfaction. Moreover, the association between medical burden and lower life satisfaction was significantly stronger for insecure than for secure participants. Our findings indicate that interventions to improve attachment security or coping processes related to attachment could help older adults retain life satisfaction.

MALDI-TOF MS fingerprinting facilitates rapid discrimination of phylotypes I, II and III of Propionibacterium acnes.

Matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is widely used today for species determination of bacteria and fungi in routine microbiological laboratories, and can also be used for subtyping of bacteria, such as Bacteroides fragilis. Propionibacterium acnes is frequently referred to as an anaerobic skin commensal of relatively low pathogenicity. In addition to its accepted pathogenic role in acne, P. acnes is now emerging as an important opportunistic pathogen in many other clinical situations, including late-stage prosthetic joint infections, osteomyelitis, endocarditis, endophthalmitis, post-neurosurgical infections and possibly prostate cancer. At the population genetic level, P. acnes can be differentiated into a number of distinct phylogroups, known as types IA1, IA2, IB, IC, II and III, which may be associated with different types of infections and clinical conditions. The aim of the present study was to evaluate MS-based typing for resolution of these genetic groups after routine identification by MALDI-TOF MS (Bruker MALDI Biotyper). The software package ClinProTools 2.2 was used to analyze the protein based mass spectra of reference strains belonging to types IA, IB, IC, II and III. Phylogroup-specific peaks and peak shifts were then identified visually. In addition, peak variations between the different types of P. acnes were investigated by using FlexAnalysis 3.3 software (Bruker). A differentiating library was created, which was used to type further 48 clinical isolates of P. acnes. Typing data obtained by MALDI-TOF MS were then compared with the results from Multilocus Sequence Typing (MLST). Most of the clinical isolates (n = 19) belonged to the type IA grouping according to MALDI-TOF MS. By MLST, all isolates were identified as type IA1. Twenty-one clinical isolates belonged to the type IB cluster based on both MALDI-TOF MS and MLST typing. Eight clinical isolates were identified as type II strains by both typing methods and all the type III reference strains could be distinguished by the presence of a unique type III-specific peak (7238 Da) by the MALDI-TOF MS. Our study demonstrates that MALDI-TOF MS is a reliable and powerful tool for rapid identification and typing of P. acnes strains from the main genetic divisions of the species.

The value of MALDI-TOF MS for the identification of clinically relevant anaerobic bacteria in routine laboratories.

Between 2010 and 2011, 283 clinically relevant non-duplicate anaerobic isolates were analysed by MALDI-TOF MS and the results were compared with conventional identification. Immediately after isolation, an ethanol precipitation was carried out on isolated colonies and the stabilized samples were anonymized and sent to the laboratory of Bruker Daltonik, Bremen, Germany, where the identification was done using the standard protocol for micro-organism identification on a Microflex LT mass spectrometer equipped with the MALDI Biotyper 3.0 software. Of 283 isolates, 218 (77 %) were identified at species level [log(score) ≥2.0], 31 isolates (10.95 %) were identified at genus level [log(score) 1.7-2.0] and 34 (12 %) gave non-reliable identification [log(score) <1.7]. Out of the 31 isolates with log(score) 1.7-2.0, in the case of 24 isolates the species name given by the MALDI Biotyper was accepted if it was the same as for the classical identification. Of 218 isolates identified at species level, 40 results were discordant with phenotypic identification, and of the 31 isolates identified at genus level according to the manufacturer's score cut-off, four gave results discordant with the phenotypic method. For the 44 discordant results, 16S rRNA gene sequencing confirmed MALDI-TOF MS identification in 41 cases, leaving three isolates (0.7 %) that had been misidentified by MALDI-TOF MS.

Differentiation of division I (cfiA-negative) and division II (cfiA-positive) Bacteroides fragilis strains by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is increasingly used in clinical microbiological laboratories to identify bacteria and fungi at a species level and to subtype them. The cfiA gene encoding the unique carbapenemases found in Bacteroides is restricted to division II Bacteroides fragilis strains. The aim of this study was to evaluate whether MALDI-TOF MS is suitable for differentiating B. fragilis strains which harbour the cfiA gene from those that do not. A well-defined collection of 40 B. fragilis isolates with known imipenem MICs (0.062->32 mg l(-1)) were selected for this study. Twelve B. fragilis strains with known cfiA status, including NCTC 9343 (division I) and TAL3636 (division II), were measured by means of microflex LT MALDI-TOF MS and well-defined differences in mass spectra between the cfiA-positive and cfiA-negative strains were found in the interval 4000-5500 Da. A further 28 strains were selected for the blind measurements: 9 cfiA-positive clinical isolates with different imipenem MICs ranging between 0.06 and >32 mg l(-1) (different expressions of the metallo-ß-lactamase gene) were clearly separated from the 19 cfiA-negative isolates. The presence or absence of the selected peaks in all tested strains clearly differentiated the strains belonging to B. fragilis division I (cfiA-negative) or division II (cfiA-positive). These results suggest a realistic method for differentiating division II B. fragilis strains (harbouring the cfiA gene) and to determine them at a species level at the same time. Although not all cfiA-positive B. fragilis strains are resistant to carbapenems, they all have the possibility of becoming resistant to this group of antibiotics by acquisition of an appropriate IS element for full expression of the cfiA gene, leading to possible treatment failure.

Sex differences in the variables associated with objectively measured moderate-to-vigorous physical activity in preschoolers.

OBJECTIVE: To investigate variables associated with objectively measured moderate-to-vigorous physical activity (MVPA) in German preschool children. METHODS: Cross-sectional data was collected from 649 three to six year old children (51% boys) in 52 preschools in south Germany between autumn and spring 2008-2009. Sociodemographic, health and socio-cultural variables that could affect children's objectively measured MVPA minutes, averaged over two to four week and weekend days, were tested in bivariate and multivariate linear regression models. RESULTS: MVPA was significantly associated with the extrinsic variables age (-4.52 min/year of age), health status (5.62 min/category), high TV time (9.22 min/category) and high parental PA (6.59 min/category) among girls. For boys, only the intrinsic variable desire to be active (5.19 min/category) was significantly, positively associated with MVPA. The final models for girls and boys explained approximately 10% and 7% of the variance, respectively, in children's MVPA. CONCLUSION: We found differences by sex in variables associated with objectively measured MVPA in preschoolers. A focus on extrinsic motivators such as parental PA for girls and intrinsic motivators for boys may be an important consideration when designing interventions and PA programs for this age group.

Combining accelerometry and HR for assessing preschoolers' physical activity.

PURPOSE: With rising obesity and rapidly decreasing levels of physical activity (PA) in young children, accurate PA measurement is needed for early screening and intervention evaluation. Although the combination of accelerometry (ACC) with HR recordings is accurate in assessing PA intensity in older children, its utility in correctly classifying PA in preschoolers is unknown. METHODS: Thirty-three children (64% were boys) were recruited from four German preschools. Data included direct observation and Actiheart (CamNtech, Cambridge, UK) monitoring during 2.5 T 0.7 h (derivation data) and 1.5 T 0.3 h (validation data). Observers assessed PA using the Children's Activity Rating Scale (CARS). Moderate-to-vigorous PA (MVPA) was defined by a CARS score of 4 or 5, and sedentary behavior (SB) was defined by a CARS score of 1 or 2. Actiheart recordings were linked to CARS level, with means and 95% confidence intervals calculated for ACC and HR at each observed CARS level and for MVPA/SB. Using receiver operating characteristic analysis, gender-specific ACC and HR cutoffs for correctly classifying MVPA and SB were first determined in a derivation data set and then tested in a separate validation data set of observations. RESULTS: By combining HR and ACC cutoffs, 91% and 87% of the 15-s intervals observed as MVPA were correctly classified in girls and boys, respectively. Although generally lower, correct classification rates for SB were highest when only ACC cutoffs were applied (69% for girls and 67% for boys) rather than when combined cutoffs were used. CONCLUSIONS: Devices that combine HR and ACC data yield an accurate classification of MVPA in preschoolers but perform less well for classifying SB. These differences underscore the need to match evaluation methods with the objectives of future PA interventions.

Health, medical risk factors, and bicycle use in everyday life in the over-50 population.

Few middle-aged and elderly people get enough exercise from sports or leisure-time physical activity. Therefore, the impact of everyday physical activity on health is a matter of interest. The main objective of this study was to establish whether bicycle use in everyday life is positively associated with health. A sample of 982 randomly selected men and 1,020 women age 50-70 were asked in a computer-assisted telephone interview to provide information including a self-assessment of their health and physical activity. Self-assessed health correlates positively with bicycle use in everyday life (OR = 1.257; 95% CI: 1.031-1.532). Likewise, people who regularly cycle for transport are less likely to have medical risk factors (OR = 0.794; 95% CI: 0.652-0.967). This negative correlation is not diminished when sporting activity is controlled for. This indicates that positive effects of physical activity on risk factors can be also achieved solely by integrating more physical activity into routine everyday life.

The effect of insulin and glucose levels on retinal glial cell activation and pigment epithelium-derived fibroblast growth factor-2.

PURPOSE: The diabetic retina exhibits decreases in endogenous nonangiogenic neurotrophins. This study hypothesized that deficiencies in systemic and retinal pigment epithelium-derived (RPE) neurotrophic factors also influence retinal changes in diabetes. METHODS: Diabetes was established in Listar hooded rats with streptozotocin. Reverse transcriptase coupled polymerase chain reaction (RT-PCR) and immunoblotting were used to determine the expression of fibroblast growth factor-2 (FGF-2) in the retina and RPE, and glial fibrillary acid protein (GFAP) in the retina. In addition, primary human RPE cultures and a transformed Müller cell line were used to determine the effect of insulin, glucose, and insulin-like growth factor (IGF) on the expression of these substances. RESULTS: FGF-2 and GFAP were increased in retina, but FGF-2 was decreased in the RPE of diabetic animals. Retinal GFAP correlated with RPE FGF-2 expression in these animals. Insulin produced a dose-dependent increase in FGF-2 in RPE cells and decrease in GFAP in Müller cells grown in 15 mM glucose. In 5 mM glucose, insulin had no effect on expression of either protein. Physiological levels of insulin inhibited changes induced by 15 mM glucose. The effect of 9 nM insulin on each culture was mimicked by 1 nM IGF, and blocked with an IGFR-1 inhibitor. CONCLUSIONS: It is suggested that decreased systemic insulin and high glucose levels contribute to decreased FGF-2 production in the RPE and increased glial cell activation in the diabetic retina. Addition of insulin and IGF act to reverse this effect through the IGFR-1. These mechanisms may contribute to the development of diabetic retinopathy.

Algumas reflexões sobre produção da categoria de gênero em contextos como o movimento feminista e o poder judiciário / Some reflections on the production of the gender category in contexts such as the feminist movement and the judiciary

Pensando na discussão instaurada com a modernidade (em distintos contextos sociais), sobre a constituição dos sujeitos de direitos humanos universais, o presente trabalho buscará refletir sobre o indivíduo em sua interface com a busca de "cidadania" e do "acesso à justiça". Para tanto, analisaremos três casos concretos: duas conferências de Políticas para Mulheres, tidas aqui como rituais do movimento feminista no Brasil. Ambas dizem respeito à relação entre políticas para mulheres em duas perspectivas não-excludentes; uma delas entre as próprias mulheres - lésbicas, heterossexuais, brancas, negras, deficientes - e suas tensões direcionadas ora aos direitos individuais, ora aos direitos coletivos, num momento de discussão por cotas. A outra conferência aborda a tensão entre sexo e gênero, entre diferença como sinônimo de desigualdade. O terceiro caso retrata um julgamento de guarda e responsabilidade voltado à não-concessão da maternidade a uma mulher homossexual, mas seu deferimento ao pai tido como biológico. Por fim, sugerimos pensar como, nos dois contextos rituais distintos (Judiciário e Movimento Feminista), a categoria de gênero é produzida e se produz atrelada ao binômio biológico "macho e fêmea".

Concerning the discussion arisen by modern times (in different social contexts), about the constitution of universal human rights subjects, this paper aims to reflect upon the individual and his search for "citizenship" and "access to justice". Three cases will be analyzed: two conferences on Women"s Politics, important in the Brazilian feminist movement. Both concern the relation among women"s politics within two non exclusive perspectives: one among women themselves - lesbians, heterosexual, white, black. handicapped - and their tensions related either to individual rights or to collective rights, in a time when quotas are being discussed. The other conference approaches the tension between sex and gender, difference as synonymous with inequality. The third case is about a judgment of guard and responsibility, when maternity of a homosexual woman is restrained, but is allowed to the biological father. At last, we propose the reflection on how, in the two distinct ritual contexts (the Judiciary and the Feminist Movement), the gender category is produced along with the biological binomial - male and female.

Prevalence of physical activity among the working population and correlation with work-related factors: results from the first German National Health Survey.

This paper investigates levels of engagement in physical activity (PA) among the total German working population and for specific subgroups. The first national health survey for the Federal Republic of Germany was conducted from October 1997 to March 1999. The following study is based on a representative net sample of 3,323 employed persons aged 18 to 69. Bivariate methods and multiple logistic regression analyses were used to investigate the relationship between PA and workplace and occupational factors in addition to social and lifestyle-specific correlates. Four out of 10 gainfully employed persons (39.2%) do not engage in sport. Those with physically strenuous jobs and frequent overtime work are significantly less likely to engage in leisure-time PA. Non-manual workers, and younger, unmarried workers are particularly likely to have an active lifestyle. Our study population did not correspond to the popular image of the recreational athlete as an abstinent, "ascetic" individual: The subgroups of non-smokers and teetotalers contained significantly fewer athletes than the corresponding reference groups. The present paper is the first to publish representative data on PA in the working population since German reunification in 1990. The data show that workers with a high risk of morbidity are those least likely to engage in leisure-time PA (manual workers with below-average educational qualifications from lower socioeconomic groups). The significant accumulation of socially depriving living conditions and lifestyle deficits among inactive subjects shows that one-off preventive measures intended to motivate sporting activity are likely to be ineffective in these subgroups of the population. We therefore advocate continuous exercise programs near the workplace involving exercise training suited to the particular occupation, dietary advice, relaxation techniques and occupational medical care.

Phospholipid profile in tracheal aspirates of very preterm neonates: effect of prenatal betamethasone administration.

We compared the phospholipid profile in tracheal aspirates from surfactant-treated preterm neonates with and without prenatal betamethasone administration. We found higher phosphatidylglycerol concentrations and lower phosphatidylinositol and sphingomyelin concentrations in corticosteroid-treated preterms ( P < 0.01). We speculate that prenatal corticosteroids enhance biochemical surfactant phospholipid maturation.

Polymorphisms of surfactant protein B encoding gene: modifiers of the course of neonatal respiratory distress syndrome?

UNLABELLED: Surfactant protein B (SP-B) is a lipophilic protein and plays a major role in lung mechanics. Polymorphisms of surfactant protein A, another component of the surfactant system, have been previously described to be a risk factor for respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) in preterms. The aim of this prospective study was to determine whether polymorphisms within intron 4 of the SP-B gene are related to the incidence, severity and complications of RDS in Caucasian newborns. In order to identify SP-B intron 4 polymorphisms, we analysed genomic DNA by means of polymerase chain reaction, fragment length and sequence analysis in 140 preterms and 58 healthy term neonates. The frequency of intron 4 variations did not differ between preterms and terms. A total of 111 preterms with the intron 4 wild type (group 1) and 29 preterms carrying the genetic variations (group 2) did not differ in gestational age, gender distribution and birth weight. Compared to group 1, the overall incidence of RDS (75.7% versus 93.1%, P < 0.05), the frequency of severe RDS (28.4% versus 55.2%, P < 0.01) and BPD (21.6% versus 48.3%, P < 0.01) were all higher in group 2. The median duration of oxygen dependency (4 days versus 17 days, P < 0.05) and the need for surfactant administration were also higher in group 2 than in group 1 (43.2% versus 72.4%, P < 0.01). Duration of mechanical ventilation and rate of chronic lung disease at 36 weeks were comparable in both groups. CONCLUSION: we suggest that polymorphisms in intron 4 of the surfactant protein B gene independently modify the course of neonatal respiratory distress syndrome.