A national qualitative investigation of the impact of service change on doctors' training during Covid-19.

BACKGROUND: The Covid-19 crisis sparked service reconfigurations in healthcare systems worldwide. With postgraduate medical education sitting within these systems, service reconfigurations substantially impact trainees and their training environment. This study aims to provide an in-depth qualitative understanding of the impact of service reconfiguration on doctors' training during the pandemic, identifying opportunities for the future as well as factors that pose risks to education and training and how these might be mitigated. METHODS: Qualitative parallel multi-centre case studies examined three Trusts/Health Boards in two countries in the United Kingdom. Data were collected from online focus groups and interviews with trainees and supervisors using semi-structured interview guides (September to December 2020). A socio-cultural model of workplace learning, the expansive-restrictive continuum, informed data gathering, analysis of focus groups and coding. RESULTS: Sixty-six doctors participated, representing 25 specialties/subspecialties. Thirty-four participants were male, 26 were supervisors, 17 were specialty trainees and 23 were foundation doctors. Four themes described the impact of pandemic-related service reconfigurations on training: (1) Development of skills and job design, (2) Supervision and assessments, (3) Teamwork and communication, and (4) Workload and wellbeing. Service changes were found to both facilitate and hinder education and training, varying across sites, specialties, and trainees' grades. Trainees' jobs were redesigned extensively, and many trainees were redeployed to specialties requiring extra workforce during the pandemic. CONCLUSIONS: The rapid and unplanned service reconfigurations during the pandemic caused unique challenges and opportunities to doctors' training. This impaired trainees' development in their specialty of interest, but also presented new opportunities such as cross-boundary working and networking.

Gender, power and leadership: the effect of a superior's gender on respiratory therapists' ability to challenge leadership during a life-threatening emergency.

BACKGROUND: Effective communication within teams is crucial, especially in crisis situations. Hierarchy gradients between team members can contribute to communication failures and are influenced by many factors. The effect of gender on team performance has not been well studied. The objective of this study was to examine the effect of the physician's gender on respiratory therapists' ability to effectively challenge clearly incorrect clinical decisions during a life-threatening crisis. METHODS: Respiratory therapists were recruited to take part in a high-fidelity simulation of can't-intubate can't-oxygenate scenarios. They were randomized into two groups, either assisting a male or a female anaesthetist in managing an airway crisis during which the anaesthetist made incorrect clinical decisions. Two independent raters scored the performances using the modified Advocacy-Inquiry Score (min 1, max 6). RESULTS: Twenty-nine subjects completed the study. The median best challenge score when the staff anaesthetist was female was 4 (3-5 IQR [2-6 range]) compared with 3 (3-3[0-3]) for challenges to a male anaesthetist (P=0.017). The median of the total challenges against a female staff member 11 (7.3-14.8 [2-18]) was significantly higher compared with 4 (3.5-7 [2-11.5]) for a male staff (P=0.006). CONCLUSIONS: The study showed a significant effect of superiors' gender on a respiratory therapist's ability to challenge leadership. A female staff anaesthetist was challenged more often and with greater assertiveness and effectiveness. This has implications for an educational intervention targeting the ability to challenge a wrong decision by a supervisor and emphasizing the effect of gender on the willingness to speak up.

Effects of vagus nerve stimulation on extinction of conditioned fear and post-traumatic stress disorder symptoms in rats.

Exposure-based therapies help patients with post-traumatic stress disorder (PTSD) to extinguish conditioned fear of trauma reminders. However, controlled laboratory studies indicate that PTSD patients do not extinguish conditioned fear as well as healthy controls, and exposure therapy has high failure and dropout rates. The present study examined whether vagus nerve stimulation (VNS) augments extinction of conditioned fear and attenuates PTSD-like symptoms in an animal model of PTSD. To model PTSD, rats were subjected to a single prolonged stress (SPS) protocol, which consisted of restraint, forced swim, loss of consciousness, and 1 week of social isolation. Like PTSD patients, rats subjected to SPS show impaired extinction of conditioned fear. The SPS procedure was followed, 1 week later, by auditory fear conditioning (AFC) and extinction. VNS or sham stimulation was administered during half of the extinction days, and was paired with presentations of the conditioned stimulus. One week after completion of extinction training, rats were given a battery of behavioral tests to assess anxiety, arousal and avoidance. Results indicated that rats given SPS 1 week prior to AFC (PTSD model) failed to extinguish the freezing response after eleven consecutive days of extinction. Administration of VNS reversed the extinction impairment and attenuated reinstatement of the conditioned fear response. Delivery of VNS during extinction also eliminated the PTSD-like symptoms, such as anxiety, hyperarousal and social avoidance for more than 1 week after VNS treatment. These results provide evidence that extinction paired with VNS treatment can lead to remission of fear and improvements in PTSD-like symptoms. Taken together, these findings suggest that VNS may be an effective adjunct to exposure therapy for the treatment of PTSD.

Tackling agricultural diffuse pollution: What might uptake of farmer-preferred measures deliver for emissions to water and air?

Mitigation of agricultural diffuse pollution poses a significant policy challenge across Europe and particularly in the UK. Existing combined regulatory and voluntary approaches applied in the UK continue to fail to deliver the necessary environmental outcomes for a variety of reasons including failure to achieve high adoption rates. It is therefore logical to identify specific on-farm mitigation measures towards which farmers express positive attitudes for higher future uptake rates. Accordingly, a farmer attitudinal survey was undertaken during phase one of the Demonstration Test Catchment programme in England to understand those measures towards which surveyed farmers are most receptive to increasing implementation in the future. A total of 29 on-farm measures were shortlisted by this baseline farm survey. This shortlist comprised many low cost or cost-neutral measures suggesting that costs continue to represent a principal selection criterion for many farmers. The 29 measures were mapped onto relevant major farm types and input, assuming 95% uptake, to a national scale multi-pollutant modelling framework to predict the technically feasible impact on annual agricultural emissions to water and air, relative to business as usual. Simulated median emission reductions, relative to current practise, for water management catchments across England and Wales, were estimated to be in the order sediment (20%)>ammonia (16%)>total phosphorus (15%) ≫ nitrate/methane (11%)>nitrous oxide (7%). The corresponding median annual total cost of the modelled scenario to farmers was £3 ha(-1)yr(-1), with a corresponding range of -£84 ha(-1)yr(-1) (i.e. a net saving) to £33 ha(-1)yr(-1). The results suggest that those mitigation measures which surveyed farmers are most inclined to implement in the future would improve the environmental performance of agriculture in England and Wales at minimum to low cost per hectare.

Power and conflict: the effect of a superior's interpersonal behaviour on trainees' ability to challenge authority during a simulated airway emergency.

A key factor that may contribute to communication failures is status asymmetry between team members. We examined the effect of a consultant anaesthetist's interpersonal behaviour on trainees' ability to effectively challenge clearly incorrect clinical decisions. Thirty-four trainees were recruited to participate in a video-recorded scenario of an airway crisis. They were randomised to a group in which a confederate consultant anaesthetist's interpersonal behaviour was scripted to recreate either a strict/exclusive or an open/inclusive communication dynamic. The scenario allowed trainees four opportunities to challenge clearly wrong decisions. Performances were scored using the modified Advocacy-Inquiry Score. The highest median (IQR [range]) score was 3.0 (2.2-4.0 [1.0-5.0]) in the exclusive communication group, and 3.5 (3.0-4.5 [2.5-6.0]) in the inclusive communication group (p = 0.06). The study did not show a significant effect of consultant behaviour on trainees' ability to challenge their superior. It did demonstrate trainees' inability to challenge their seniors effectively, resulting in critical communication gaps.

Cardiopulmonary exercise variables are associated with postoperative morbidity after major colonic surgery: a prospective blinded observational study.

BACKGROUND: Postoperative complications are associated with reduced fitness. Cardiopulmonary exercise testing (CPET) has been used in risk stratification. We investigated the relationship between preoperative CPET and in-hospital morbidity in major colonic surgery. METHODS: We prospectively studied 198 patients undergoing major colonic surgery (excluding neoadjuvant cancer therapy), performing preoperative CPET (reported blind to clinical state), and recording morbidity (assessed blind to CPET), postoperative outcome, and length of stay. RESULTS: Of 198 patients, 62 were excluded: 11 had emergency surgery, 25 had no surgery, 23 had incomplete data, and three were unable to perform CPET. One hundred and thirty-six (89 males, 47 females) were available for analysis. The median age was 71 [inter-quartile range (IQR) 62-77] yr. Sixty-five patients (48%) had a complication at day 5 after operation. Measurements significantly lower in patients with complications than those without were O2 uptake (VO2) at estimated lactate threshold (θ(L)) [median 9.9 (IQR 8.3-12.7) vs 11.2 (9.5-14.2) ml kg(-1) min(-1), P<0.01], VO2 at peak [15.2 (12.6-18.1) vs 17.2 (13.7-22.5) ml kg(-1) min(-1), P=0.01], and ventilatory equivalent for CO2 (V(E)/VCO2) at θ(L) [31.3 (28.0-34.8) vs 33.9 (30.0-39.1), P<0.01]. A final multivariable logistic regression model contained VO2 at θ(L) {one-point change odds ratio (OR) 0.77 [95% confidence interval (CI) 0.66-0.89], P<0.0005; two-point change OR 0.61 (0.46-0.81) and gender [OR 4.42 (1.78-9.88), P=0.001]}, and was reasonably able to discriminate those with and without complications (AUC 0.71, CI 0.62-0.80, 68% sensitivity, 65% specificity). CONCLUSIONS: CPET variables are associated with postoperative morbidity. A multivariable model with VO2 at θ(L) and gender discriminates those with complications after colonic surgery.

The first confirmed cases of full albinism in rajid species.

Three albino skate specimens (Rajidae) were captured from the North Sea and English Channel between 2008 and 2011. Using DNA barcoding (COI gene) and morphometric analyses, species were identified as a spotted ray Raja montagui, a blonde ray Raja brachyura and a thornback ray Raja clavata. This finding represents the first record of full albinism (a lack of skin and retinal pigmentation) in rajid species.

Heterogeneity of colorectal cancer (CRC) in reference to KRAS proto-oncogene utilizing WAVE technology.

BACKGROUND: New drugs targeting specific genes required for unregulated growth and metastases have improved survival rates for patients with metastatic colorectal cancer. Resistance to monoclonal antibodies specific for the epidermal growth factor receptor (EGFR) has been attributed to the presence of activating point mutations in the proto-oncogene KRAS. The use of EGFR inhibitor monotherapy in patients that have KRAS wild type has produced response rates of only 10-20%. The molecular basis for clinical resistance remains poorly understood. We propose two possible explanations to explain these low response rates; 1) levels of resistant CRC cells carrying mutated KRAS are below the sensitivity of standard direct sequencing modalities (<5%) or 2) the standard practice of analyzing a single area within a heterogeneous tumor is a practice that can overlook areas with mutated KRAS. METHODS: In a collaborative effort with the surgical and molecular pathology departments, 3 formalin fixed paraffin embedded tissue blocks of human CRC were obtained from the human tissue bank maintained by the Lifespan Pathology Department and/or the human tissue bank maintained by the Molecular Pathology Core of the COBRE for Cancer Research Development. The three specimens previously demonstrated KRAS mutations detected by the Applied Biosystems Kit. The Wave system 4500 (high performance ion-pairing liquid chromatography (IP-HPLC)) was utilized to evaluate tissue for the presence of KRAS proto-oncogene mutations at codons 12 and 13. RESULTS: Initially, the sensitivity of WAVE technology was compared with direct sequencing by evaluating a dilutional series. WAVE detected mutant alleles at levels of 2.5% compared to 20% performed with standard direct sequencing. Samples from three patients were evaluated by WAVE technology. Eight samples from patient 1 were analyzed. In two of eight samples, no mutations were detected at concentrations as low as 5%. In one sample a mutation was noted by WAVE and not by direct sequencing. All four samples from patient 2 tested positive for Exon 12/13 mutations. Of the seven samples from patient 3, five were positive for Exon 12/13 mutations and two were negative for Exon 12/13 mutations. CONCLUSION: In these studies the analysis of three patients' colorectal cancer tissues were analyzed utilizing the WAVE technology. Results demonstrated a greater degree of sensitivity in mutation detection when compared to standard sequencing. These studies also demonstrated heterogeneity of expression of KRAS mutations between areas of the tissue samples at a genomic level. The low clinical response rates to EGFR inhibition might be explained by the variation in mutation presence, which was dependent upon the region examined. The heterogeneity demonstrated in these studies provides another phenotypic variant that will impact clinical care.

Difficult airway management and the novice physician.

BACKGROUND: Selection of the ideal airway device in patients with difficult airways (DA) or potentially difficult airways remains controversial, especially, for a novice anesthesia physician (NP) who must deviate from conventional direct laryngoscopy with a rigid laryngoscope following a failed intubation and employ one of the several alternative devices. The author determines and compares tracheal intubation success rates, times to success and complications of a novice physician using four alternative airway devices in 20 obese (BMI more than 27.5) patients who may be more difficult to intubate than normal weight patients. MATERIALS AND METHODS: In this prospective randomized experimental study the author investigates a novice physician's use of the Bullard, Fiberoptic, Fastrach and Trachlight comparing reliability, rapidity and safety of orotracheal intubations. Following induction of anesthesia the NP was allowed up to a maximum of two attempts per device at oral intubation. Mean intubation times plus/minus SD, per cent success rates and postoperative complications were evaluated for each device. RESULTS: The Fastrach was successful 100% of the time on the first attempt requiring a mean time of 55 seconds plus/minus 6.6. All intubations were unsuccessful following two attempts with the Fiberoptic. A success rate of 20% (one of five) was achieved with the Trachlight on first attempt after 95 seconds. The Bullard was successful in 40 % (two of five) of the patients after a mean time 60 seconds plus/minus five, but was the only device to result in mild oral discomfort one day post operatively. CONCLUSIONS: In the hands of a novice physician managing a difficult or potentially difficult airway, often encountered in obese patients, the Fastrach demonstrated the highest success rate.

Low genetic diversity in a snail intermediate host (Biomphalaria pfeifferi Krass, 1848) and schistosomiasis transmission in the Senegal River Basin.

Population genetic perturbations of intermediate hosts, often a consequence of human pressure on environmental resources, can precipitate unexpectedly severe disease outbreaks. Such disturbances are set to become increasingly common following range changes concomitant with climate shifts, dwindling natural resources and major infrastructure changes such as hydroprojects. Construction of the Diama dam in the Senegal River Basin (SRB) reduced river salinity, enabling the freshwater snail intermediate host Biomphalaria pfeifferi to rapidly expand its distribution. A serious public health problem ensued, with an epidemic of intestinal schistosomiasis occurring in the previously schistosome-free Richard-Toll region within 2 years. The current study aimed to assess the population variability of B. pfeifferi in the SRB, and speculate upon its subsequent impact on host-parasite interactions following such engineered ecological change. Genetic variation at nine polymorphic microsatellite loci revealed little population differentiation in SRB snails compared with those from natural habitats in Zimbabwe, where Schistosoma mansoni transmission is much lower. 'Open' SRB habitats are associated with greater water contact, smaller population sizes and less genetic diversity, with sites downstream of Richard-Toll showing greater inter- and intrapopulation variation, concomitant with less frequent human contact. These observations may be explained by rapid expansion into pristine habitat selecting for high fecundity genotypes at the expense of schistosome resistance, presenting S. mansoni with genetically homogenous highly fecund susceptible populations around the focal point, promoting development of a highly compatible host-parasite relationship. Longitudinal study of such systems may prove important in predicting public health risks engendered by future environmental engineering projects.

Size-dependent growth of individual Atlantic salmon Salmo salar alevins from hatch to first feeding.

Variation in egg size, hatch timing and size at hatch, and their influence on individual growth rates of Atlantic salmon Salmo salar alevins up to first feeding were examined in pure strain and hybrid crosses of fish from Scotland and Canada. At the intra-female, intra-cross type and inter-cross type levels, specific growth rates prior to first feed were strongly size dependent, with smaller and later hatching alevins growing significantly faster. The magnitude of this size-dependent growth was greatest in the hybrid crosses. This resulted in a 40% reduction in the coefficient of variation (c.v.) in alevin size from post-hatch to first feeding at the intra-female level, and a reduction of both intra- and inter-cross differences in alevin sizes in the same period.

Communication skills training in postgraduate medicine: the development of a new course.

It has long been accepted that communication is of central importance in healthcare, and a core aspect of clinical competence. Many educational institutions and Royal Colleges now reflect this and consider communication skills a priority in postgraduate examination. The new examination "Practical Assessment of Clinical and Examination Skills" has replaced the Royal College of Physicians MRCP part 2 clinical and oral examination. This examination now consists of five clinical stations, two of which focus on communication skills. A short course for postgraduate trainees has been designed to address the communication skills requirements of the part 2 clinical examination. The aims, development, and content of the course are described. Emphasis is placed on candidates practising skills with patients and receiving feedback during the course. Evidence suggests that practice with feedback is an essential ingredient of communication skills courses, and is more effective than other methods such as observing experts or video examples, or simply discussing issues in communication. Results of a preliminary evaluation indicate that the course was perceived as valuable by candidates and that the aims, format, and content were appropriate. Although the preliminary evaluation was largely positive, it could be argued that the acid test of the effectiveness of a course is an objective evaluation of skills, observed before and after the course, a development that is being considered for future evaluation of the course. Recommendations for applying this type of training to postgraduate trainees in any branch of medicine are given.

Breeding system and demography shape population genetic structure across ecological and climatic zones in the African freshwater snail, Bulinus forskalii (Gastropoda, Pulmonata), intermediate host for schistosomes.

The role of breeding system and population bottlenecks in shaping the distribution of neutral genetic variation among populations inhabiting patchily distributed, ephemeral water bodies was examined for the hermaphroditic freshwater snail Bulinus forskalii, intermediate host for the medically important trematode Schistosoma guineensis. Levels of genetic variation at 11 microsatellite loci were assessed for 600 individuals sampled from 19 populations that span three ecological and climatic zones (ecozones) in Cameroon, West Africa. Significant heterozygote deficiencies and linkage disequilibria indicated very high selfing rates in these populations. Despite this and the large genetic differentiation detected between populations, high levels of genetic variation were harboured within these populations. The high level of gene flow inferred from assignment tests may be responsible for this pattern. Indeed, metapopulation dynamics, including high levels of gene flow as well as extinction/contraction and recolonization events, are invoked to account for the observed population structuring, which was not a consequence of isolation-by-distance. Because B. forskalii populations inhabiting the northern, Sahelian area are subject to more pronounced annual cycles of drought and flood than the southern equatorial ones, they were expected to be subject to population bottlenecks of increased frequency and severity and, therefore, show reduced genetic variability and elevated population differentiation. Contrary to predictions, the populations inhabiting the most northerly ecozone exhibited higher genetic diversity and lower genetic differentiation than those in the most southerly one, suggesting that elevated gene flow in this region is counteracting genetic drift.

Plant-like mating in an animal: sexual compatibility and allocation trade-offs in a simultaneous hermaphrodite with remote transfer of sperm.

The importance of sexual compatibility between mates has only recently been realized in zoological research into sexual selection, yet its study has been central to botanical research for many decades. The reproductive characteristics of remote mating, an absence of precopulatory mate screening, internal fertilization and embryonic brooding are shared between passively pollinated plants and a phylogenetically diverse group of sessile aquatic invertebrates. Here, we further characterize the sexual compatibility system of one such invertebrate, the colonial ascidian Diplosoma listerianum. All 66 reciprocal pairings of 12 genetic individuals were carried out. Fecundities of crosses varied widely and suggested a continuous scale of sexual compatibility. Of the 11 animals from the same population c. 40% of crosses were completely incompatible with a further c. 20% having obvious partial compatibility (reduced fecundity). We are unaware of other studies documenting such high levels of sexual incompatibility in unrelated individuals. RAPD fingerprinting was used to estimate relatedness among the 12 individuals after a known pedigree was successfully reconstructed to validate the technique. In contrast to previous results, no correlation between genetic similarity and sexual compatibility was detected. The blocking of many genotypes of sperm is expected to severely modify realized paternity away from 'fair raffle' expectations and probably reduce levels of intra-brood genetic diversity in this obligatorily promiscuous mating system. One adaptive benefit may be to reduce the bombardment of the female reproductive system by outcrossed sperm with conflicting evolutionary interests, so as to maintain female control of somatic : gametic investment.

The expression of immune-regulatory genes in rainbow trout, Oncorhynchus mykiss, during a natural outbreak of proliferative kidney disease (PKD).

Proliferative kidney disease (PKD) is a parasitic infection of salmonid fish characterized by an apparently abnormal immune response to the presence of the myxozoan parasite, Tetracapsuloides bryosalmonae. In order to examine the nature of the immune response at the molecular level, the expression of a range of immune regulatory genes, including cytokines and cyclooxygenase (COX)-2 was examined in naive unexposed fish and in naive fish exposed to parasite-infected water at three points during the course of a natural outbreak of PKD. Since fish with advanced PKD pathology generally exhibit increased susceptibility to secondary infections which is typical of stress/cortisol-mediated immune suppression, a further aim of this work was to examine in vitro the influence of the glucocorticoid cortisol on the bacterial lipopolysaccharide (LPS)-induced expression of the trout cytokine genes studied. Two weeks after the initial sampling, naive exposed fish showed a specific profile of up-regulated tumor necrosis factor (TNF)-alpha2, COX-2 and, to a lesser extent, transforming growth factor (TGF)-beta1 expression. As the disease pathology increased, TNF-alpha2 and COX-2 expression returned to normal levels. Stress levels of cortisol suppressed the LPS inducibility of pro-inflammatory cytokine genes, although TGF-beta1 and TNF-alpha2 appeared to be refractory. These data demonstrate that specific immune responses at the molecular level are affected during PKD infection, with the cortisol suppression of cytokine expression in vitro providing a possible link to PKD-mediated cytokine down-regulation and immune suppression.

Frequency dependence in matings with water-borne sperm.

Negative frequency-dependent mating success--the rare male effect--is a potentially powerful evolutionary force, but disagreement exists as to whether previous work, focusing on copulating species, has robustly demonstrated this phenomenon. Noncopulating sessile organisms that release male gametes into the environment but retain their eggs for fertilization may routinely receive unequal mixtures of sperm. Although promiscuity seems unavoidable it does not follow that the resulting paternity obeys 'fair raffle' expectations. This study investigates frequency dependence in the mating of one such species, the colonial ascidian Diplosoma listerianum. In competition with an alternative sperm source males fathered more progeny if previously mated to a particular female than if no mating history existed. This suggests positive frequency-dependent selection, but may simply result from a mate order effect involving sperm storage. With fewer acclimation matings, separated by longer intervals, this pattern was not found. When, in a different experimental design, virgin females were given simultaneous mixtures of gametes at widely divergent concentrations, sperm at the lower frequency consistently achieved a greater than expected share of paternity--a rare male effect. A convincing argument as to why D. listerianum should favour rare sperm has not been identified, as sperm rarity is expected to correlate very poorly with ecological or genetic male characteristics in this pattern of mating. The existence of nongenetic female preferences at the level of colony modules, analogous in effect to fixed female preferences, is proposed. If visible to selection, indirect benefits from increasing the genetic diversity of a sibship appear the only likely explanation of the rare male effect in this system as the life history presents virtually no costs to multiple mating, and a near absence of direct (resource) benefits, whereas less controversial hypotheses of female promiscuity (e.g. trade up, genetic incompatibility) do not seem appropriate.

Regional vulnerability after traumatic brain injury: gender differences in mice that overexpress human copper, zinc superoxide dismutase.

Neuronal loss was quantified in both cortical and subcortical brain regions after traumatic brain injury in male and female nontransgenic (nTg) and transgenic (Tg) mice that overexpress human copper, zinc superoxide dismutase. Mice were euthanized at 7 days after a controlled cortical impact injury. Sections of brain were processed for immunolocalization of NeuN, a neuronal nuclear antigen, and the complement type 3 receptor, a marker of microglia/macrophages, and stained for iron. Cortical lesion volume and neuronal loss in the medial and/or lateral ventroposterior thalamic nuclei were significantly less in the nTg female compared to the nTg male (P = 0.0373 and P = 0.0023, respectively). In contrast, in CA3 of the hippocampus and laterodorsal thalamic nucleus (LD), there were no gender differences in neuronal loss between these nTg groups. Cortical lesion volume was significantly reduced in Tg males compared to nTg males (P = 0.0137) and was unchanged in the Tg females compared to the nTg females. Neuronal loss was attenuated in the CA3 and LD in the Tg females compared to the nTg females (P = 0.0252 and P = 0.0244, respectively). A similar protection was not observed in the Tg males. Microglial activation paralleled the pattern of neuronal loss and was most consistently aligned with iron deposition in the cortex and hippocampus. No overt differences were found in the pattern of microglial activation or iron staining between nTg and Tg mice nor between genders. Our findings demonstrate that neuroprotection, afforded by overexpression of copper, zinc superoxide dismutase, exhibits both regional and gender specificity.

The effects of intrauterine cocaine exposure on the respiratory status of the very low birth weight infant.

OBJECTIVES: This study examined the effects of intrauterine cocaine exposure on very low birth weight infants with respect to their surfactant requirement and need for ventilatory support. STUDY DESIGN: A retrospective cohort study was conducted on infants with birth weight between 750 and 1500 g admitted to the neonatal intensive care unit between January 1992 and January 1995. RESULTS: Of the 149 infants studied, 48 infants were exposed only to cocaine and 101 infants had no drug exposure. There were no significant differences between the two groups for gestational age, sex, abruptio placenta, prolonged rupture of membranes, and antenatal steroid usage. The cocaine-exposed group had a significantly greater birth weight (1190 vs. 1109, p<0.02), less prenatal care (48% vs. 14%, p<0.00007), older maternal age (30 vs. 24, p<0.00002), more black race (79% vs. 57%, p<0.01), and more rapid plasma reagin (RPR) positivity (25% vs. 2%, p<0.00006). There were no significant differences in median APGAR scores, or incidence of necrotizing enterocolitis, retinopathy of prematurity (ROP), intraventricular hemorrhage (IVH), and bronchopulmonary dysplasia (BPD) between the two groups. Cocaine-exposed infants received surfactant treatment less often (73% vs. 48%, p<0.0035), received fewer mean doses of surfactant (0.4 vs. 10.0, p<0.0014), and were intubated less frequently (44% vs. 65%, p<0.012). There was no significant difference between groups for intubation at 24 and 48 hours and for the development of bronchopulmonary dysplasia. CONCLUSION: Perinatal cocaine exposure appears to have some significant short-term effects on the need for surfactant replacement therapy and need for initial intubation in respiratory distress syndrome (RDS) but no overall effect on the development of BPD.