Prophylactic antibiotic use in acellular dermal matrix-assisted implant-based breast reconstruction.

BACKGROUND: Prophylactic antibiotics are used in acellular dermal matrix-assisted implant-based breast reconstructions. However, there are no universally accepted guidelines regarding the best regimen. This retrospective, multicentre study was designed to compare the different prophylactic antibiotic regimens in these patients in three hospitals across two NHS trusts over a five-year period. METHODS: Case notes and electronic records were reviewed for all patients undergoing acellular dermal matrix-assisted implant-based breast reconstructions between January 2010 and December 2014. Prophylactic antibiotic regimens, duration of use, wound infection, implant loss, seroma and therapeutic antibiotic use was recorded. Patients were divided into groups based on prophylactic antibiotic regimen and actual duration of use. Intergroup analysis was performed using Stata 13.0. Implant loss due to infection was the primary outcome measure. RESULTS: A total of 105 patients had 122 breast reconstructions performed over the study period. Four prophylactic antibiotic regimens were identified: single dose (n = 20), three doses (n = 17), antibiotics for five-seven days (n = 51) and antibiotics until drains removed (n = 32). There was no statistically significant difference (p > 0.05) between the various regimens in implant loss, wound infection, therapeutic antibiotic prescription or seroma rates. Based on the actual duration of prophylactic antibiotics usage, three groups were identified: prophylactic antibiotics given for one day (n = 26), antibiotics for up to one week (n = 76) and for more than one week (n = 13). Again, no statistically significant difference was observed in the groups for any outcome measure. CONCLUSION: The study demonstrated no difference in outcomes between different prophylactic antibiotic regimens in acellular dermal matrix-assisted implant-based breast reconstructions.

Nanosecond pulse shaping at 780 nm with fiber-based electro-optical modulators and a double-pass tapered amplifier.

We describe a system for generating frequency-chirped and amplitude-shaped pulses on time scales from sub-nanosecond to ten nanoseconds. The system starts with cw diode-laser light at 780 nm and utilizes fiber-based electro-optical phase and intensity modulators, driven by an arbitrary waveform generator, to generate the shaped pulses. These pulses are subsequently amplified to several hundred mW with a tapered amplifier in a delayed double-pass configuration. Frequency chirps up to 5 GHz in 2 ns and pulse widths as short as 0.15 ns have been realized.

The impact of prenatal and neonatal infection on neurodevelopmental outcomes in very preterm infants.

OBJECTIVE: Determine the association of prenatal and neonatal infections with neurodevelopmental outcomes in very preterm infants. STUDY DESIGN: Secondary retrospective analysis of 155 very preterm infants at a single tertiary referral center. General linear or logistic regression models were used to evaluate the association with hospital factors; brain injury, growth and development; and neurobehavioral outcome. RESULT: Necrotizing enterocolitis with sepsis was associated with reduced transcerebellar diameter (38.3 vs 48.4 mm, P<0.001) and increased left ventricular diameter (12.0 vs 8.0 mm, P=0.005). Sepsis alone was associated with higher diffusivity in the left frontal lobe (1.85 vs 1.68 × 10⁻³ mm² s⁻¹, P=0.001) and right cingulum bundle (1.52 vs 1.45 × 10⁻³ mm 253 s⁻¹, P=0.002). Neurobehavioral outcomes were worse in children exposed to maternal genitourinary infection (cognitive composite: ß=-8.8, P=0.001; receptive language score: ß=-2.7, P<0.001; language composite: ß=-14.9, P<0.001) or histological chorioamnionitis (language composite: ß=-8.6, P=0.006), but not neonatal infection. CONCLUSION: Neonatal infection was associated with changes in brain structure but not with neurobehavioral outcomes, whereas the opposite pattern was observed for maternal genitourinary tract infection. These findings emphasize the potential importance of infections during pregnancy on the neurodevelopmental outcomes of preterm infants.

Maternal obesity and increased risk for autism and developmental delay among very preterm infants.

OBJECTIVE: Thirty-five percent of women of child-bearing age are obese, and there is evidence that maternal obesity may increase the risk for adverse neurodevelopmental outcome. However, research regarding obesity and neurodevelopment among children born preterm is limited. This study aimed to determine associations between maternal obesity and neurodevelopment in very preterm children at age 2 years. STUDY DESIGN: Maternal/infant dyads (n=62) born ⩽30 weeks gestation were enrolled in a prospective cohort study at a level-III neonatal intensive care unit. Mothers were classified as obese or non-obese based on pre-pregnancy body mass index. Infants underwent magnetic resonance imaging at term equivalent and developmental testing at age 2. Maternal obesity was investigated for associations with neurodevelopment. RESULT: Maternal obesity was associated with positive screen for autism (odds ratio=9.88, P=0.002) and lower composite language scores (ß=-9.36, (confidence interval=-15.11, -3.61), P=0.002). CONCLUSION: Maternal obesity was associated with adverse neurodevelopmental outcome at age 2 in this cohort of very preterm children. This study requires replication, but may support targeted surveillance of infants born to women with maternal obesity.

Novel Vitamin K analogs suppress seizures in zebrafish and mouse models of epilepsy.

Epilepsy is a debilitating disease affecting 1-2% of the world's population. Despite this high prevalence, 30% of patients suffering from epilepsy are not successfully managed by current medication suggesting a critical need for new anti-epileptic drugs (AEDs). In an effort to discover new therapeutics for the management of epilepsy, we began our study by screening drugs that, like some currently used AEDs, inhibit histone deacetylases (HDACs) using a well-established larval zebrafish model. In this model, 7-day post fertilization (dpf) larvae are treated with the widely used seizure-inducing compound pentylenetetrazol (PTZ) which stimulates a rapid increase in swimming behavior previously determined to be a measurable manifestation of seizures. In our first screen, we tested a number of different HDAC inhibitors and found that one, 2-benzamido-1 4-naphthoquinone (NQN1), significantly decreased swim activity to levels equal to that of valproic acid, 2-n-propylpentanoic acid (VPA). We continued to screen structurally related compounds including Vitamin K3 (VK3) and a number of novel Vitamin K (VK) analogs. We found that VK3 was a robust inhibitor of the PTZ-induced swim activity, as were several of our novel compounds. Three of these compounds were subsequently tested on mouse seizure models at the National Institute of Neurological Disorders and Stroke (NINDS) Anticonvulsant Screening Program. Compound 2h reduced seizures particularly well in the minimal clonic seizure (6Hz) and corneal-kindled mouse models of epilepsy, with no observable toxicity. As VK3 affects mitochondrial function, we tested the effects of our compounds on mitochondrial respiration and ATP production in a mouse hippocampal cell line. We demonstrate that these compounds affect ATP metabolism and increase total cellular ATP. Our data indicate the potential utility of these and other VK analogs for the prevention of seizures and suggest the potential mechanism for this protection may lie in the ability of these compounds to affect energy production.

Factors associated with feeding difficulties in the very preterm infant.

AIM: To investigate early medical and family factors associated with later feeding risk in preterm infants. METHODS: For this longitudinal study, 136 infants born ≤30 weeks gestation were enrolled. Medical and social background factors were assessed at term equivalent age. Infants underwent magnetic resonance imaging, neurobehavioral evaluation and feeding assessment. Parent involvement in the neonatal intensive care unit was tracked, and maternal mental health was assessed at neonatal intensive care unit discharge. At age 2 years, feeding outcome was assessed using the Eating Subscale of the Infant-Toddler Social Emotional Assessment (n = 80). Associations between feeding problems at age 2 years and (i) early medical factors, (ii) neurobehavioral functioning and feeding at term equivalent age, (iii) cerebral structure and (iv) maternal mental health were investigated using regression. RESULTS: Eighteen (23%) children had feeding problems at age 2 years. Feeding problems were associated with early hypotonia (p = 0.03; ß = 0.29) and lower socio-economic status (p = 0.046; ß = -0.22). No associations were observed between early medical factors, early feeding performance, cerebral structure alterations or maternal well-being and feeding outcome. CONCLUSION: Early hypotonia may disrupt the development of oral-motor skills. Hypotonia and poor feeding also may share a common aetiology. Associations with lower socio-economic status highlight the potential influence of family background factors in feeding problems in the preterm infant.

Identifying mothers of very preterm infants at-risk for postpartum depression and anxiety before discharge.

OBJECTIVE: We investigated whether particular demographics, maternal psychosocial and infant factors identified mothers of very preterm infants at risk for postpartum depression or anxiety at the time of discharge from a level III urban Neonatal Intensive Care Unit (NICU). STUDY DESIGN: A racially diverse cohort of mothers (N=73) of preterm infants (gestational age <30 weeks) completed a comprehensive questionnaire at discharge from the NICU assessing postpartum depression, anxiety and psychosocial and demographic factors. Additionally, infants underwent brain magnetic resonance imaging before discharge. RESULT: Twenty percent of mothers had clinically significant levels of depression whereas 43% had moderate to severe anxiety. Being married (P<0.01), parental role alteration (P<0.01) and prolonged ventilation (P<0.05) were associated with increased depressive symptoms. No psychosocial, demographics or infant factors, including severity of brain injury, were associated with state anxiety levels. CONCLUSION: Maternal factors, such as marital status, stress from parental role alteration and infant factors, such as prolonged ventilation, are associated with increased depression. However, clinically significant levels of anxiety are common in mothers of very preterm infants with few identifiable risk factors. These findings support the need for universal screening within the NICU.

Creation of arbitrary time-sequenced line spectra with an electro-optic phase modulator.

We use a waveguide-based electro-optic phase modulator, driven by a nanosecond-timescale arbitrary waveform generator, to produce an optical spectrum with an arbitrary pattern of peaks. A programmed sequence of linear voltage ramps, with various slopes, is applied to the modulator. The resulting phase ramps give rise to peaks whose frequency offsets relative to the carrier are equal to the slopes of the corresponding linear phase ramps. This simple extension of the serrodyne technique provides multi-line spectra with peak spacings in the 100 MHz range.

Characterization and compensation of the residual chirp in a Mach-Zehnder-type electro-optical intensity modulator.

We utilize various techniques to characterize the residual phase modulation of a waveguide-based Mach-Zehnder electro-optical intensity modulator. A heterodyne technique is used to directly measure the phase change due to a given change in intensity, thereby determining the chirp parameter of the device. This chirp parameter is also measured by examining the ratio of sidebands for sinusoidal amplitude modulation. Finally, the frequency chirp caused by an intensity pulse on the nanosecond time scale is measured via the heterodyne signal. We show that this chirp can be largely compensated with a separate phase modulator. The various measurements of the chirp parameter are in reasonable agreement.

Molecular prognostic indicators in breast cancer.

Here we review a panel of oncogene products, proteases and markers of proliferation that have shown potential as prognostic indicators in primary breast cancer. The relative merits of specific genetic mutations as well as alterations at the protein level are discussed. Finally an assessment is made of the transfer of knowledge from the laboratory to the bed-side.

Fuc-TVII is required for T helper 1 and T cytotoxic 1 lymphocyte selectin ligand expression and recruitment in inflammation, and together with Fuc-TIV regulates naive T cell trafficking to lymph nodes.

To determine how the alpha(1,3)fucosyltransferases Fuc-TIV and Fuc-TVII, and the selectin ligands they control may contribute to the adaptive immune response, contact hypersensitivity (CHS) was characterized in mice deficient in either or both enzymes. We find a substantial CHS deficiency in Fuc-TVII(-/-) mice, and a complete deficiency in Fuc-TIV(-/-)/Fuc-TVII(-/-) mice. These defects are not accounted for by alterations in the number or function of epidermal Langerhans cells required for cutaneous antigen processing and presentation. By contrast, defective CHS in Fuc-TVII(-/-) mice or Fuc-TIV(-/-)/Fuc-TVII(-/-) mice is attributed in part to prominent, or nearly complete deficiencies, respectively, in the complement of naive T lymphocytes available in lymph nodes for antigen-dependent activation, expansion, differentiation, and dissemination. Fuc-TVII deficiency also deletes expression of E- and P-selectin ligands by Th1 and T cytotoxic 1 (Tc1) lymphocytes, annuls T cell trafficking to inflamed cutaneous sites in vivo, and thereby controls an essential component of the efferent phase of the cutaneous immune response. These observations indicate that collaborative contributions of Fuc-TIV and Fuc-TVII to L-selectin ligand synthesis, and to lymphocyte recruitment, are requisite components of the primary cellular immune response, and assign an essential role to Fuc-TVII in control of E- and P-selectin ligand expression by Th1 and Tc1 lymphocytes.

The alpha(1,3)fucosyltransferases FucT-IV and FucT-VII exert collaborative control over selectin-dependent leukocyte recruitment and lymphocyte homing.

E-, P-, and L-selectin counterreceptor activities, leukocyte trafficking, and lymphocyte homing are controlled prominently but incompletely by alpha(1,3)fucosyltransferase FucT-VII-dependent fucosylation. Molecular determinants for FucT-VII-independent leukocyte trafficking are not defined, and evidence for contributions by or requirements for other FucTs in leukocyte recruitment is contradictory and incomplete. We show here that inflammation-dependent leukocyte recruitment retained in FucT-VII deficiency is extinguished in FucT-IV(-/-)/FucT-VII(-/-) mice. Double deficiency yields an extreme leukocytosis characterized by decreased neutrophil turnover and increased neutrophil production. FucT-IV also contributes to HEV-born L-selectin ligands, since lymphocyte homing retained in FucT-VII(-/-) mice is revoked in FucT-IV(-/-)/FucT-VII(-/-) mice. These observations reveal essential FucT-IV-dependent contributions to E-, P-, and L-selectin ligand synthesis and to the control of leukocyte recruitment and lymphocyte homing.

Hair analysis does not support hypothesized arsenic and chromium exposure from drinking water in Woburn, Massachusetts.

We hypothesized that residents of Woburn, Massachusetts, had been exposed to as much as 70 microg/l of arsenic (As) and 240 microg/l of chromium (Cr) in drinking water from municipal supply wells G and H. To test this hypothesis, we measured the concentrations of As and Cr in 82 hair samples donated by 56 Woburn residents. Thirty-six samples were cut between 1964 and 1979, the period during which wells G and H were in operation. The remainder were cut either before 1964 (1938-1963; n = 26) or after 1979 (1982-1994; n = 20). Washed hair samples were analyzed by instrumental neutron activation. Exposure to the well water--measured as access--was estimated using well pumping records and a model of the Woburn water distribution system. Our results show that access to wells G and H water was not significantly correlated (95% confidence interval) with As and Cr concentrations measured in the hair of Woburn residents, but As concentrations have declined significantly over the last half century. Linear regression of As concentrations (micrograms per gram) upon year of hair cut and access to wells G and H water yielded a standard coefficient for year of -0. 0074 +/- 0.0017 (standard error; p = 2.5 -multiple- 10(-5)) and -0.12 +/- 0.10 (p = 0.22) for access. The r2 value for the model was 0.19. The geometric mean concentrations (geometric standard deviation) of As and Cr in the hair of residents who had access (i.e., relative access estimate >0) to wells G and H water (n = 27) were 0.14 (2.6) and 2.29 (1.8) microg/g, respectively; the geometric mean concentrations of As and Cr in all of the hair samples from residents who did not have access (1938-1994; n = 55) were 0.13 (3.0) and 2.19 (2.0) microg/g, respectively.

The establishment of current opinion within consultants in paediatric dentistry in the UK for the taking of dental radiographs of children.

There is an increasing realization that every effort should be made to minimize the exposure to ionizing radiation of patients and members of the dental team. There are, however, few published guidelines to assist the general practitioner in deciding whether or not radiographs are needed. There is even less information concerning the taking of dental radiographs of children. Using the Delphi Technique this study set out to seek a consensus amongst Consultant Paediatric Dentists (n = 36) working in the UK as to when dental radiographs should and should not be taken of children cared for within general dental services. A two-stage questionnaire was used and a response of 94% and 76% was obtained in the first and second questionnaire respectively. A consensus view was reached regarding whether or not radiographs should be taken in a series of 17 specific clinical situations.

The alpha(1,3)fucosyltransferase Fuc-TVII controls leukocyte trafficking through an essential role in L-, E-, and P-selectin ligand biosynthesis.

alpha(1,3)Fucosylated oligosaccharides represent components of leukocyte counterreceptors for E- and P-selectins and of L-selectin ligands expressed by lymph node high endothelial venules (HEV). The identity of the alpha(1,3)fucosyltransferase(s) required for their expression has been uncertain, as has a requirement for alpha(1,3)fucosylation in HEV L-selectin ligand activity. We demonstrate here that mice deficient in alpha(1,3) fucosyltransferase Fuc-TVII exhibit a leukocyte adhesion deficiency characterized by absent leukocyte E- and P-selectin ligand activity and deficient HEV L-selectin ligand activity. Selectin ligand deficiency is distinguished by blood leukocytosis, impaired leukocyte extravasation in inflammation, and faulty lymphocyte homing. These observations demonstrate an essential role for Fuc-TVII in E-, P-, and L-selectin ligand biosynthesis and imply that this locus can control leukocyte trafficking in health and disease.

Flow cytometric analysis of human bone marrow perfusion cultures: erythroid development and relationship with burst-forming units-erythroid.

Flow cytometry has been used in recent years to study antigenic and physical changes accompanying hematopoietic cell differentiation. Such studies have provided the basis for rapid and objective assays that are potential alternatives to the colony assays currently in widespread use. In this report, erythropoiesis was examined in growth factor-supplemented perfused cultures of bone marrow mononuclear cells (BMMNC) using flow cytometric analysis of the transferrin receptor (CD71), glycophorin antigen expression occurred with time, Initially, fewer than 10% of the cells were (CD71++, but by day 8, 19-34% of the cells were CD71++gly A-. This was followed by the appearance of gly A on 10-60% of the CD71++ cells. After day 10, CD71 expression on many gly A+ cells decreased so that a population of CD71-gly A+ cells (11-54 accumulated by day 14. Each phenotype was sorted for morphologic identification and colony assay analysis. CD71++gly A- cells were 85% blasts, one-half of which were erythroblasts, and were significantly enriched for burst-forming units-erythroid (BFU-E). The time-varying number of CD71++gly A- cells in these cultures was found to correlate with the number of BF.78-0.97). Three-color analysis was next used to examine CD33 expression on BFU-E, and in fresh BM, most were found to be CD33-. During culture, however, the number of BFU-E recovered from CD33+ populations first increased and then decreased. Therefore, CD33 was not particularly useful for identifying BFU-E. In contrast, CFU-GM were mostly found to be in the CD71+CD33+ population throughout the culture period. When erythropoietin (Epo) was not added to these cultures, the percentage of gly A+ cells was reduced from 33 to 3.3%. Further, the omission of Epo caused an 80% decrease in the number of BFU-E and a corresponding 94% decrease in the number of CD71++gly A- cells, thereby maintaining the relationship between CD71++gly A- cells and BFU-E. Therefore, flow cytometric analysis was found to be useful in assessing erythroid development, and this approach may be used to develop flow cytometric assays for other populations of interest in hematopoietic cell cultures.

Ectoparasitic acugutturid nematodes of adult lepidoptera.

Noctuidonema guyaneme is an interesting ectoparasite of adult Lepidoptera that feeds on hosts from at least five families with its long stylet. Noctuidonema guyanense spends its entire life on the adult moth and is sustained as it is passed from moth to moth during host mating. Overlapping host generations are essential for parasite survival. This nematode occurs throughout tropical and subtropical America and is transported by at least one of its hosts, Spodoptera frugiperda, during migration to northern sites in the United States each spring. Noctuidonema guyanense debilitates its hosts. Research conducted to help determine the biological control importance of this nematode is reviewed. Two additional species, N. daptria and N. dibolia, are now known for Noctuidonema.

Magnetic resonance imaging of endocrine tumours of the pancreas.

Seven patients who had functioning or non-functioning endocrine pancreatic tumours were investigated by magnetic resonance imaging. Combinations of fat suppressed T1 weighted spin echo and gradient recalled echo (n = 7), T2 weighted spin echo (n = 3) and gadolinium diethylamine triamine pentaacetic acid (Gd-DTPA) enhanced fat suppressed T1 images were acquired. Magnetic resonance imaging detected five of seven tumours prospectively (three of which were smaller than 10 mm) and a further 10 mm tumour retrospectively. Tumours were low signal on T1 weighted images and showed enhancement after Gd-DTPA. On T2 weighted images one tumour was hyperintense, and two were isointense with normal pancreas. Computed tomography, transabdominal ultrasound and angiography were performed in six patients but detected only one tumour each. Intraoperative palpation and ultrasound detected all tumours. If pre-operative imaging is required magnetic resonance imaging is the technique of choice to detect small endocrine pancreatic tumours.

Noctuidonema dibolia n. sp. (Aphelenchida: Acugutturidae), an Ectoparasite of the moth Mocis latipes (Lepidoptera: Noctuidae).

Noctuidonema dibolia n. sp., an ectoparasite of adults of the noctuid moth Mocis latipes (Guenée) is described. The differentiating characters are a club-shaped body with a subterminal vulva in the female, spicules with a reduced matrix and sheath and closely apposed dorsal and ventral arms in the male, very long stylet and conus, moderately prominent stylet knobs, a bluntly rounded head, and a large renette cell in both sexes. Lateral fields, rectum, anus, bursa, and gubernaculum are absent. Noctuidonema dibolia differs from the other species of the subfamily Noctuidonematinae in the size and robustness of the body, the length of the stylet and conus, the length of the tail, and the shape of the spicules.

Experimental in vivo generation of intertypic recombinant strains of HSV in the mouse.

The primary replication of one strain of HSV was generally unaffected by the simultaneous inoculation of another strain either at the same site or at a different site within the same dermatome. Exceptions to this were the result of the generation of intertypic recombinants which were readily isolated only from sensory ganglia 5 and 6 days after inoculation with a mixture of HSV-1 and HSV-2 and from explant culture of the resultant latently infected ganglia. By restriction enzyme analysis the majority of the recombinant strains from primary infection were characterized as HSV 1; all those from latently infected ganglia were characterized as type 2.