Limited evidence of autocorrelation signaling upcoming affective episodes: a 12-month e-diary study in patients with bipolar disorder.

BACKGROUND: Increased autocorrelation (AR) of system-specific measures has been suggested as a predictor for critical transitions in complex systems. Increased AR of mood scores has been reported to anticipate depressive episodes in major depressive disorder, while other studies found AR increases to be associated with depressive episodes themselves. Data on AR in patients with bipolar disorders (BD) is limited and inconclusive. METHODS: Patients with BD reported their current mood via daily e-diaries for 12 months. Current affective status (euthymic, prodromal, depressed, (hypo)manic) was assessed in 26 bi-weekly expert interviews. Exploratory analyses tested whether self-reported current mood and AR of the same item could differentiate between prodromal phases or affective episodes and euthymia. RESULTS: A total of 29 depressive and 20 (hypo)manic episodes were observed in 29 participants with BD. Self-reported current mood was significantly decreased during the two weeks prior to a depressive episode (early prodromal, late prodromal), but not changed prior to manic episodes. The AR was neither a significant predictor for the early or late prodromal phase of depression nor for the early prodromal phase of (hypo)mania. Decreased AR was found in the late prodromal phase of (hypo)mania. Increased AR was mainly found during depressive episodes. CONCLUSIONS: AR changes might not be better at predicting depressive episodes than simple self-report measures on current mood in patients with BD. Increased AR was mostly found during depressive episodes. Potentially, changes in AR might anticipate (hypo)manic episodes.

First-in-Human Clinical Trial to Assess the Safety, Tolerability and Pharmacokinetics of Single Doses of NTM-1633, a Novel Mixture of Monoclonal Antibodies against Botulinum Toxin E.

Botulism is a rare, life-threatening paralytic disease caused by botulinum neurotoxin (BoNT). Available treatments including an equine antitoxin and human immune globulin are given postexposure and challenging to produce and administer. NTM-1633 is an equimolar mixture of 3 human IgG monoclonal antibodies, E1, E2, and E3, targeting BoNT serotype E (BoNT/E). This first-in-human study assessed the safety, tolerability, pharmacokinetics (PK), and immunogenicity of NTM-1633. This double-blind, single-center, placebo-controlled dose escalation study randomized 3 cohorts of healthy volunteers to receive a single intravenous dose of NTM-1633 (0.033, 0.165, or 0.330 mg/kg) or saline placebo. Safety monitoring included physical examinations, clinical laboratory studies, and vital signs. Blood sampling was performed at prespecified time points for PK and immunogenicity analyses. Twenty-four subjects received study product (18 NTM-1633; 6 placebo), and no deaths were reported. An unrelated serious adverse event was reported in a placebo subject. Adverse events in the NTM-1633 groups were generally mild and similar in frequency and severity to the placebo group, and no safety signal was identified. NTM-1633 has a favorable PK profile with a half-life >10 days for the 0.330 mg/kg dose and an approximately linear relationship with respect to maximum concentration and area under the concentration-time curve (AUC0→t). NTM-1633 also demonstrated low immunogenicity. NTM-1633 is well tolerated at the administered doses. The favorable safety, PK, and immunogenicity profile supports further development as a treatment for BoNT/E intoxication and postexposure prophylaxis.

Safety, Tolerability, and Pharmacokinetics of NTM-1632, a Novel Mixture of Three Monoclonal Antibodies against Botulinum Toxin B.

Botulism is a rare, life-threatening paralytic disease caused by Clostridium botulinum neurotoxin (BoNT). Available treatments, including an equine antitoxin and human immune globulin, are given postexposure and challenging to produce and administer. NTM-1632 is an equimolar mixture of 3 human IgG monoclonal antibodies, B1, B2, and B3, targeting BoNT serotype B (BoNT/B). This first-in-human study assessed the safety, tolerability, pharmacokinetics (PK), and immunogenicity of NTM-1632. This double-blind, single-center, placebo-controlled dose escalation study randomized 3 cohorts of healthy volunteers to receive a single intravenous dose of NTM-1632 (0.033, 0.165, or 0.330 mg/kg) or saline placebo. Safety monitoring included physical examinations, clinical laboratory studies, and vital signs. Blood sampling was performed at prespecified time points for PK and immunogenicity analyses. Twenty-four subjects received study product (18 NTM-1632; 6 placebo), and no deaths or serious adverse events were reported. Adverse events in the NTM-1632 groups were generally mild and similar in frequency and severity to the placebo group, and no safety signal was identified. NTM-1632 has a favorable PK profile with a half-life of >20 days for the 0.330-mg/kg dose and an approximately linear relationship with respect to maximum concentration and area under the concentration-time curve (AUC0→t). NTM-1632 demonstrated low immunogenicity with only a few treatment-emergent antidrug antibody responses in the low and middle dosing groups and none at the highest dose. NTM-1632 is well tolerated at the administered doses. The favorable safety, PK, and immunogenicity profile of NTM-1632 supports further clinical development as a treatment for BoNT/B intoxication and postexposure prophylaxis. (This study has been registered at ClinicalTrials.gov under identifier NCT02779140.).

Visual search in ADHD, ASD and ASD + ADHD: overlapping or dissociating disorders?

Recent debates in the literature discuss commonalities between Attention-Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) at multiple levels of putative causal networks. This debate requires systematic comparisons between these disorders that have been studied in isolation in the past, employing potential markers of each disorder to be investigated in tandem. The present study, choose superior local processing, typical to ASD, and increased Intra-Subject Variability (ISV), typical to ADHD, for a head-to-head comparison of the two disorders, while also considering the comorbid cases. It directly examined groups of participants aged 10-13 years with ADHD, ASD with (ASD+) or without (ASD-) comorbid ADHD and a typically developing (TD) group (total N = 85). A visual search task consisting of an array of paired words was designed. The participants needed to find the specific pair of words, where the first word in the pair was the cue word. This visual search task was selected to compare these groups on overall search performance and trial-to-trial variability of search performance (i.e., ISV). Additionally, scanpath analysis was also carried out using Recurrence Quantification Analysis (RQA) and the Multi-Match Model. Results show that only the ASD- group exhibited superior search performance; whereas, only the groups with ADHD symptoms showed increased ISV. These findings point towards a double dissociation between ASD and ADHD, and argue against an overlap between ASD and ADHD.

Knowledge, attitudes, and practices regarding coccidioidomycosis among healthcare providers in four counties in Washington State, 2017.

Coccidioidomycosis is an emerging infection in Washington State. The epidemiology of the disease in Washington is poorly understood at present; underrecognition and underreporting of coccidioidomycosis is suspected based on reports of only severe disease. We sought to characterize healthcare provider knowledge, attitudes, and practices regarding coccidioidomycosis awareness, diagnosis, and treatment in south-central Washington. We conducted a cross-sectional survey of actively practicing healthcare providers in four counties in south-central Washington, an area recently described as endemic for Coccidioides. Survey results were used to assess awareness of reporting requirements, confidence in ability to diagnose and treat, confidence that knowledge is current, calculated knowledge score, and consideration of risk in patient population. The majority of respondents were unaware of the reporting requirement for coccidioidomycosis in Washington and further unaware that the disease had been reported in the state. Less than a third of survey respondents reported confidence in their ability to diagnose coccidioidomycosis and confidence that their knowledge is current. The majority of respondents never or rarely consider a diagnosis of coccidioidomycosis, and <25% of respondents indicated a working knowledge of serologic tests for the infection. The average knowledge score for respondents was 65%. Previous education, training, or practice regarding coccidioidomycosis was the only identified predictor of confidence and consideration of risk. These data indicate the substantial need for education and training among healthcare providers in south-central Washington and support the concern that a small proportion of existing cases of coccidioidomycosis are reported to the health department.

Loss of B Cells in Patients with Heterozygous Mutations in IKAROS.

BACKGROUND: Common variable immunodeficiency (CVID) is characterized by late-onset hypogammaglobulinemia in the absence of predisposing factors. The genetic cause is unknown in the majority of cases, and less than 10% of patients have a family history of the disease. Most patients have normal numbers of B cells but lack plasma cells. METHODS: We used whole-exome sequencing and array-based comparative genomic hybridization to evaluate a subset of patients with CVID and low B-cell numbers. Mutant proteins were analyzed for DNA binding with the use of an electrophoretic mobility-shift assay (EMSA) and confocal microscopy. Flow cytometry was used to analyze peripheral-blood lymphocytes and bone marrow aspirates. RESULTS: Six different heterozygous mutations in IKZF1, the gene encoding the transcription factor IKAROS, were identified in 29 persons from six families. In two families, the mutation was a de novo event in the proband. All the mutations, four amino acid substitutions, an intragenic deletion, and a 4.7-Mb multigene deletion involved the DNA-binding domain of IKAROS. The proteins bearing missense mutations failed to bind target DNA sequences on EMSA and confocal microscopy; however, they did not inhibit the binding of wild-type IKAROS. Studies in family members showed progressive loss of B cells and serum immunoglobulins. Bone marrow aspirates in two patients had markedly decreased early B-cell precursors, but plasma cells were present. Acute lymphoblastic leukemia developed in 2 of the 29 patients. CONCLUSIONS: Heterozygous mutations in the transcription factor IKAROS caused an autosomal dominant form of CVID that is associated with a striking decrease in B-cell numbers. (Funded by the National Institutes of Health and others.).

[Ambulatory monitoring and digital phenotyping in the diagnostics and treatment of bipolar disorders]. / Ambulantes Monitoring und digitale Phänotypisierung in Diagnostik und Therapie bipolarer Erkrankungen.

BACKGROUND: Reliable and valid diagnostics and treatment of bipolar disorders and affective episodes are subject to extensive, especially methodological limitations in the clinical practice. OBJECTIVE: The use of smartphones and mobile sensor technology for improvement in diagnostics and treatment of bipolar disorders. METHODS: Critical discussion of current research on the use of ambulatory monitoring and digital phenotyping with bipolar disorders. RESULTS: In many studies the observation periods were too short and the sensors applied were too inaccurate to enable reliable and valid detection of behavioral changes in the context of affective episodes. CONCLUSION: The clarification and operationalization of psychopathological constructs to allow for the measurement of objectively observable and ascertainable behavioral changes during depressive and (hypo)manic states are essential for the successful application of modern mobile technologies in the diagnostics and treatment of bipolar disorders.

Expanding the clinical spectrum of biallelic ZNF335 variants.

ZNF335 plays an essential role in neurogenesis and biallelic variants in ZNF335 have been identified as the cause of severe primary autosomal recessive microcephaly in 2 unrelated families. We describe, herein, 2 additional affected individuals with biallelic ZNF335 variants, 1 individual with a homozygous c.1399 T > C, p.(Cys467Arg) variant, and a second individual with compound heterozygous c.2171_2173delTCT, p.(Phe724del) and c.3998A > G, p.(Glu1333Gly) variants with the latter variant predicted to affect splicing. Whereas the first case presented with early death and a severe phenotype characterized by anterior agyria with prominent extra-axial spaces, absent basal ganglia, and hypoplasia of the brainstem and cerebellum, the second case had a milder clinical presentation with hypomyelination and otherwise preserved brain structures on MRI. Our findings expand the clinical spectrum of ZNF335-associated microcephaly.

Productive efficiency and its determinants in the Community Dental Service in the north-west of England.

OBJECTIVES: To assess the efficiency of service provision in the Community Dental Services and its determinants in the North-West of England. SETTING AND SAMPLE: 40 Community Dental Services sites operating across the North-West of England. BASIC RESEARCH DESIGN: A data envelopment analysis was undertaken of inputs (number of surgeries, hours worked by dental officers, therapists, hygienists and others) and outputs (treatments delivered, number of courses of treatment and patients seen) of the Community Dental Services to produce relative efficiency ratings by health authority. These were further analyzed in order to identify which inputs (determined within the Community Dental Services) or external factors outside the control of the Community Dental Services are associated with efficiency. MAIN OUTCOME MEASURE: Relative efficiency rankings in Community Dental Services production of dental healthcare. RESULTS: Using the quantity of treatments delivered as the measure of output, on average the Community Dental Services in England is operating at a relative efficiency of 85% (95% confidence interval 77%- 99%) compared to the best performing services. Average efficiency is lower when courses of treatment and unique patients seen are used as output measures, 82% and 68% respectively. Neither the input mix nor the patient case mix explained variations in the efficiency across Community Dental Services. CONCLUSIONS: Although large variations in performance exist across Community Dental Services, the data available was not able to explain these variations. A useful next step would be to undertake detailed case studies of several best and under-performing services to explore the factors that influence relative performance levels.

Bringing inorganic chemistry to life with inspiration from R. J. P. Williams.

Our appreciation of the scholarly ideas and thinking of Bob Williams is illustrated here by a few of the areas in which he inspired us. His journey to bring inorganic chemistry to life began with an early interest in analytical chemistry, rationalising the relative stabilities of metal coordination complexes (The Irving-Williams Series), and elucidating the organometallic redox chemistry of vitamin B12. He (and Vallee) recognised that metal ions are in energised (entatic) states in proteins and enzymes, which themselves are dynamic structures of rods and springs. He played a key role in helping Rosenberg to pave the road toward the clinic for the anticancer drug cisplatin. He believed that evolution is not just dependent on DNA, but also on the metallome. Organisms and the environment are one system: does DNA code directly for all the essential elements of life?

Low-dose aspirin use does not diminish the immune response to monovalent H1N1 influenza vaccine in older adults.

Non-steroidal anti-inflammatory drugs (NSAIDs) may inhibit antibody production by peripheral blood mononuclear cells; one consequence of this could be decreased effectiveness of vaccines in NSAID users. Because many older adults use low-dose aspirin for primary or secondary prevention of coronary events, any inhibitory effect of aspirin on vaccine immune response could reduce the benefits of vaccination programmes in older adults. We tested whether immune response to vaccination differed between users vs. non-users of low-dose aspirin, using data from four randomized trials of monovalent 2009 pandemic influenza A(H1N1) vaccine. Geometric mean haemagglutination inhibition antibody titres were not significantly lower in low-dose aspirin users compared to non-users. Our results provide reassurance that influenza vaccination effectiveness is probably not reduced in older adults taking chronic low-dose aspirin.

Carboxylated and uncarboxylated forms of osteocalcin directly modulate the glucose transport system and inflammation in adipocytes.

Osteocalcin is secreted by osteoblasts and improves insulin sensitivity in vivo, although mechanisms remain unclear. We tested the hypothesis that osteocalcin directly modulates cell biology in insulin-targeted peripheral tissues. In L-6 myocytes, osteocalcin stimulated glucose transport both in the absence (basal) and presence of insulin. Similarly, in primary cultured adipocytes, both carboxylated and uncarboxylated osteocalcin increased basal and insulin-stimulated glucose transport as well as insulin sensitivity. Osteocalcin also increased basal and insulin-stimulated glucose oxidation, though there was no effect on fatty acid synthesis or lipolysis. In primary-cultured adipocytes, both forms of osteocalcin suppressed secretion of tumor necrosis factor alpha into the media; however, only carboxylated osteocalcin suppressed interleukin 6 release, and neither form of osteocalcin modulated monocyte chemoattractant protein-1 secretion. Both carboxylated and uncarboxylated osteocalcin increased secretion of adiponectin and the anti-inflammatory cytokine interleukin 10. In conclusion, both carboxylated and uncarboxylated osteocalcin directly increase glucose transport in adipocytes and muscle cells, while suppressing proinflammatory cytokine secretion and stimulating interleukin 10 and adiponectin release. Thus, these results provide a mechanism for the insulin-sensitizing effects of osteocalcin and help elucidate the role that bone plays in regulating systemic metabolism.

Bedside ultrasound of the neck confirms endotracheal tube position in emergency intubations.

PURPOSE: In controlled environments such as the operating room, bedside ultrasound (BUS) of the neck has shown high accuracy for distinguishing endotracheal (ETI) from esophageal intubations. We sought to determine the accuracy of BUS for endotracheal tube (ETT) position in the emergency department (ED) setting. MATERIALS AND METHODS: We assessed the utility of BUS in a single-center observational study in an ED setting. BUS was performed either simultaneously with ED intubation (S/ED), within < 3 minutes of ED intubation (A/ED), or in < 3 minutes of patient's ED arrival after pre-hospital intubation (A/EMS). Trained ED providers performed BUS; intubators were blinded to ultrasound findings. We used Cormack and Lehane categories (CL) to classify intubation attempts as "easy" (CL-I/II), "moderate" (CL-III) and "difficult" (CL-IV). Additional data included the diagnostic accuracy of the sonographer and intubator compared to the clinical outcome, anatomy identified by sonography and time to diagnosis. RESULTS: During a 10-month period, 89 subjects with 115 intubation attempts were included in the study, and 86 patients/101 attempts with complete data were used in the study (63-easy, 19-moderate, 19-difficult). The sonographers achieved 100 % accuracy with respect to determining the correct ETT position utilizing an anterior neck approach, while the intubators' accuracy in assessing correct tube location was 97 % compared to the clinical outcome. A blinded review of sonography findings confirmed all BUS anatomical findings. A sonographically empty esophagus was 100 % specific for endotracheal intubation, and a "double trachea sign" was 100 % sensitive and 91 % specific for esophageal intubation. The sonographic time to diagnosis was significantly faster than the intubator time to diagnosis ("easy" p < 0.001; n = 47; "moderate" p = 0.001; n = 15; "difficult" p < 0.001; n = 19); Wilcoxon test; A/EMS cases excluded). CONCLUSION: In this emergency setting, ultrasound determined ETT locations rapidly with 100 % accuracy and independently of the CL-category.

Establishing semi-automated infection surveillance in obstetrics and gynaecology.

BACKGROUND: Surveillance is an acknowledged method to decrease nosocomial infections, such as surgical site infections (SSIs). Electronic healthcare records create the opportunity for automated surveillance. While approaches for different types of surgeries and indicators already exist, there are very few for obstetrics and gynaecology. AIM: To analyse the sensitivity and workload reduction of semi-automated surveillance in obstetrics and gynaecology. METHODS: In this retrospective, single-centre study at a 1438-bed tertiary care hospital in Germany, semi-automated SSI surveillance using the indicators 'antibiotic prescription', 'microbiological data' and 'administrative data' (diagnosis codes, readmission, post-hospitalization care) was compared with manual analysis and categorization of all patient files. Breast surgeries (BSs) conducted in 2018 and caesarean sections (CSs) that met the inclusion criteria between May 2013 and December 2019 were included. Indicators were analysed for sensitivity, number of analysed procedures needed to identify one case, and potential workload reduction in detecting SSIs in comparison with the control group. FINDINGS: The reference standard showed nine SSIs in 416 BSs (2.2%). Sensitivities for the indicators 'antibiotic prescription', 'diagnosis code', 'microbiological sample taken', and the combination 'diagnosis code or microbiological sample' were 100%, 88.9%, 66.7% and 100%, respectively. The reference standard showed 54 SSIs in 3438 CSs (1.6%). Sensitivities for the indicators 'collection of microbiological samples', 'diagnosis codes', 'readmission/post-hospitalization care', and the combination of all indicators were 38.9%, 27.8%, 85.2% and 94.4%, respectively. CONCLUSIONS: Semi-automated surveillance systems may reduce workload by maintaining high sensitivity depending on the type of surgery, local circumstances and thorough digitalization.

Assessing the use of minimally invasive self-sampling at home for long-term monitoring of the microbiota within UK families.

Monitoring the presence of commensal and pathogenic respiratory microorganisms is of critical global importance. However, community-based surveillance is difficult because nasopharyngeal swabs are uncomfortable and painful for a wide age range of participants. We designed a methodology for minimally invasive self-sampling at home and assessed its use for longitudinal monitoring of the oral, nasal and hand microbiota of adults and children within families. Healthy families with two adults and up to three children, living in and near Liverpool, United Kingdom, self-collected saliva, nasal lining fluid using synthetic absorptive matrices and hand swabs at home every two weeks for six months. Questionnaires were used to collect demographic and epidemiological data and assess feasibility and acceptability. Participants were invited to take part in an exit interview. Thirty-three families completed the study. Sampling using our approach was acceptable to 25/33 (76%) families, as sampling was fast (76%), easy (76%) and painless (60%). Saliva and hand sampling was acceptable to all participants of any age, whereas nasal sampling was accepted mostly by adults and children older than 5 years. Multi-niche self-sampling at home can be used by adults and children for longitudinal surveillance of respiratory microorganisms, providing key data for design of future studies.

Evasion of human innate and acquired immunity by a bacterial homolog of CD11b that inhibits opsonophagocytosis.

Microbial pathogens must evade the human immune system to survive, disseminate and cause disease. By proteome analysis of the bacterium Group A Streptococcus (GAS), we identified a secreted protein with homology to the alpha-subunit of Mac-1, a leukocyte beta2 integrin required for innate immunity to invading microbes. The GAS Mac-1-like protein (Mac) was secreted by most pathogenic strains, produced in log-phase and controlled by the covR-covS two-component gene regulatory system, which also regulates transcription of other GAS virulence factors. Patients with GAS infection had titers of antibody specific to Mac that correlated with the course of disease, demonstrating that Mac was produced in vivo. Mac bound to CD16 (FcgammaRIIIB) on the surface of human polymorphonuclear leukocytes and inhibited opsonophagocytosis and production of reactive oxygen species, which resulted in significantly decreased pathogen killing. Thus, by mimicking a host-cell receptor required for an innate immune response, the GAS Mac protein inhibits professional phagocyte function by a novel strategy that enhances pathogen survival, establishment of infection and dissemination.

Social and non-social gaze cueing in autism spectrum disorder, attention-deficit/hyperactivity disorder and a comorbid group.

Recent trends in literature, along with the changes to the Diagnostic and Statistical Manual (DSM), make it imperative to study Attention-Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) together, in order to better understand potential aetiological commonalities between these highly comorbid disorders. The present study examines social cueing, a highly studied construct in ASD, and intra-subject variability (ISV), a potential endophenotype of ADHD, in four groups of typically developing (TD), ADHD, ASD- (ASD without ADHD), ASD+ (ASD with ADHD) participants (N = 85) aged 10-13 years. Results showed that social cueing is intact in the 'pure' ASD group when task expectations are clear. The ADHD group showed faster saccadic reaction times, no increased ISV and a pattern of viewing comparable to the TD group. However, the ASD + group showed a differences in processing style and ISV. A secondary analysis gives evidence of non-additive effects of the ASD and ADHD factors.

Defective membrane potential changes in neutrophils from human neonates.

In an attempt to determine the mechanism of the profound defect in chemotaxis observed in the polymorphonuclear leukocytes (PMN) of human neonates, we have examined membrane potential changes and alterations in free intracellular calcium following chemotactic factor stimulation. Following exposure to formyl-methionyl-leucyl-phenylalanine (FMLP), PMN from adult donors (11) showed a marked change in membrane potential (31%) as determined by fluorescence emission using the cyanine dye, 3-3-dipentyloxacarbocyanine [DiOC5(3)]. In marked contrast, FMLP-stimulated PMN from 10 human neonates failed to show any significant change in membrane potential (1-2%). Using the calcium-sensitive probe Quin 2/AM, FMLP induced an increase in fluorescence of up to 51% in adult PMN (10). In contrast, the change in intracellular free calcium induced in neonatal PMN was much less (32%; P less than 0.01). These results suggest that the profound defect in chemotactic responsiveness of PMN from human neonates may result from an inability of these cells to undergo changes in membrane potential following inflammatory mediator stimulation.

Human recombinant interferon gamma enhances neonatal polymorphonuclear leukocyte activation and movement, and increases free intracellular calcium.

In previous studies, we have reported that after chemotactic factor stimulation, PMNs from neonates fail to undergo certain critical activation steps. Furthermore, the concentration of free intracellular calcium reached is significantly below that of PMNs from adults. Interferon-gamma (IFN-gamma) is a lymphokine that has been shown to activate phagocytic cells, and IFN-gamma messenger RNA production by neonatal mononuclear leukocytes has been reported to be depressed. In the present studies, we found that recombinant human IFN-gamma markedly enhanced the chemotactic responses of PMNs from neonates to levels that were not different from that of PMNs from adults. Furthermore, preincubation of the neonatal cells with this recombinant human lymphokine also corrected the abnormality in intracellular calcium metabolism. These results suggest that this developmental defect in phagocytic cell movement may be the result of an intrinsic defect in IFN-gamma production resulting in deficiency of this critical phagocyte-activating lymphokine.

Fibronectin enhances the opsonic and protective activity of monoclonal and polyclonal antibody against group B streptococci.

We have investigated the opsonic and protective effects of fibronectin (FN) against type III group B streptococci. When used by itself, the FN failed to promote actual internalization of group B organisms. The addition of FN to group B streptococci that had been preopsonized in an immunoglobulin preparation modified for intravenous use ( IgIV ) or a type-specific, murine monoclonal antibody of IgG isotype markedly enhanced interaction with human polymorphonuclear leukocytes (PMN). A similar enhanced effect was observed when the FN was combined with type-specific monoclonal antibody preparations of IgM and, surprisingly, IgA isotype. Preincubation experiments indicated that the major effect was upon the PMN rather than directly on the bacteria, but we could not demonstrate an effect of FN on cell surface receptors for the Fc fragment of Ig or C3b using rosetting techniques. In addition to enhancing the in vitro opsonic activity of Ig, the FN significantly increased the protective effect of the polyclonal and monoclonal Ig preparations in an animal model of neonatal group B streptococcal disease. Thus, FN appears to have a critical role in the host defense mechanisms against group B streptococci.