Alternative splicing associated with phenotypic plasticity in the bumble bee Bombus terrestris.

Phenotypic plasticity is when one genome can produce more than one phenotype. The caste system found in many social insects is an important example of plasticity. Several studies have examined gene expression in social insect developmental and caste differences. Changes in gene expression, however, are not the only source of phenotypic plasticity. Here, we investigate the role of alternative splicing in the buff-tailed bumble bee Bombus terrestris. We found that 5,458 genes in B. terrestris (40%) express more than one isoform. Larvae have the lowest level of splicing events, followed by adults and then pupae. We found that when an isoform is expressed in a given caste in the larval stage, it tends to be expressed in all castes at the larval stage. The same is true at the pupal stage. However, we see more complicated interactions between the adult castes with reproductive females showing different isoform expression compared to nonreproductive females and male adults showing the most distinct patterns. We found 455 isoform switching genes, that is genes, where one developmental stage, sex or caste uses a specific isoform and another type uses a different isoform. Among genes displaying isoform switching are some involved in the ecdysteriod pathway, an important system in insect behaviour.

Short-term outcomes of inborn v. outborn very-low-birth-weight neonates (<1 500 g) in the neonatal nursery at Groote Schuur Hospital, Cape Town, South Africa.

BACKGROUND: The Groote Schuur Hospital (GSH) neonatal nursery provides level 3 care for the Metro West Health District in the Western Cape Province of South Africa. Worldwide, very-low-birth-weight (VLBW) neonates delivered in level 3 neonatal units have better outcomes than those transported from other facilities. OBJECTIVES: To identify the characteristics and outcomes of VLBW neonates at GSH, with emphasis on differences between inborns and outborns. METHODS: This was a retrospective cohort study. VLBW neonates admitted to the GSH neonatal nursery between 1 January 2012 and 31 December 2013 were enrolled on the Vermont Oxford Network database and reviewed. RESULTS: Of 1 032 VLBW neonates enrolled, 906 (87.8%) were delivered at GSH and 126 (12.2%) were outborn. Access to antenatal care, antenatal steroids and inborn status were statistically significant predictors of mortality and survival without morbidity. The mothers of inborn patients were more likely than those of outborn patients to have received antenatal care (89.1% v. 57.9%; p<0.0001) and antenatal steroids (64.2% v. 15.2%; p<0.0001). Inborns required less ventilatory support (16.2% v. 57.9%; p<0.0001) and surfactant administration than outborns (25.3% v. 65.1%; p<0.0001), and developed less late infection (8.8% v. 23.4%; p<0.0001), severe intraventricular haemorrhage (3.7% v. 13.9%; p<0.0001) and chronic lung disease (5.3% v. 13.4%; p=0.003). The incidence of necrotising enterocolitis was similar in the two groups (5.9% v. 8.7%; p=0.227). The mortality rate was 18.4% for inborns and 33.3% for outborns (p<0.0001). Mortality declined as birth weight increased. Of the survivors, 85.0% of inborns and 70.2% of outborns did not develop serious morbidity (p=0.003). CONCLUSIONS: VLBW neonates delivered at GSH had better outcomes than their outborn counterparts. Perinatal regionalisation is beneficial to our patients, with antenatal care, timeous transfer in utero and antenatal steroids contributing to excellent outcomes.

Short-term outcomes of inborn v. outborn very-low-birth-weight neonates (<1 500 g) in the neonatal nursery at Groote Schuur Hospital, Cape Town, South Africa

Background. The Groote Schuur Hospital (GSH) neonatal nursery provides level 3 care for the Metro West Health District in the Western Cape Province of South Africa. Worldwide, very-low-birth-weight (VLBW) neonates delivered in level 3 neonatal units have better outcomes than those transported from other facilities.Objectives. To identify the characteristics and outcomes of VLBW neonates at GSH, with emphasis on differences between inborns and outborns. Methods. This was a retrospective cohort study. VLBW neonates admitted to the GSH neonatal nursery between 1 January 2012 and 31 December 2013 were enrolled on the Vermont Oxford Network database and reviewed.Results. Of 1 032 VLBW neonates enrolled, 906 (87.8%) were delivered at GSH and 126 (12.2%) were outborn. Access to antenatal care, antenatal steroids and inborn status were statistically significant predictors of mortality and survival without morbidity. The mothers of inborn patients were more likely than those of outborn patients to have received antenatal care (89.1% v. 57.9%; p<0.0001) and antenatal steroids (64.2% v. 15.2%; p<0.0001). Inborns required less ventilatory support (16.2% v. 57.9%; p<0.0001) and surfactant administration than outborns (25.3% v. 65.1%; p<0.0001), and developed less late infection (8.8% v. 23.4%; p<0.0001), severe intraventricular haemorrhage (3.7% v. 13.9%; p<0.0001) and chronic lung disease (5.3% v. 13.4%; p=0.003). The incidence of necrotising enterocolitis was similar in the two groups (5.9% v. 8.7%; p=0.227). The mortality rate was 18.4% for inborns and 33.3% for outborns (p<0.0001). Mortality declined as birth weight increased. Of the survivors, 85.0% of inborns and 70.2% of outborns did not develop serious morbidity (p=0.003).Conclusions. VLBW neonates delivered at GSH had better outcomes than their outborn counterparts. Perinatal regionalisation is beneficial to our patients, with antenatal care, timeous transfer in utero and antenatal steroids contributing to excellent outcomes

Newborns should be receiving premedication before elective intubation.

BACKGROUND: Intubation is a common neonatal procedure. Premedication is accepted as a standard of care, but its use is not universal and wide variations exist in practice. OBJECTIVE: To evaluate current practices for premedication use prior to elective neonatal intubation in South Africa (SA). METHOD: We invited 481 clinicians to participate in a cross-sectional web-based survey. RESULTS: We received responses from 28.3% of the clinicians surveyed; 54.1% were from the private sector and 45.9% from the state sector. Most respondents worked in medium-sized neonatal units with six to ten beds. Most paediatricians (76.0%) worked in the private sector, and 78.6% of neonatologists in the state sector. Premedication was practised by 71.9% of the respondents, but only 38.5% of neonatal units had a written policy. Sedatives were used for premedication by 63.2% of the respondents. Midazolam (41.5%), morphine (34.0%) and ketamine (20.8%) were most commonly used. Muscle relaxants and atropine were not routinely administered. Suxamethonium was the muscle relaxant of choice. Varied combinations of agents or single agents were used. Midazolam used alone was the preferred option. CONCLUSION: This first survey of premedication for neonatal intubation in SA revealed variations in practice, with a minority of clinicians following a written policy. The findings can be used to benchmark practice and inform the design of local collaborative trials aimed at determining optimal premedication prior to neonatal intubation. The survey demonstrates clinicians' reluctance to participate in surveys, suggesting a need for a national collaborative network to obtain representative data.

The structured communication tool SBAR (Situation, Background, Assessment and Recommendation) improves communication in neonatology.

BACKGROUND: Effective communication, co-operation and teamwork have been identified as key determinants of patient safety. SBAR (Situation, Background, Assessment and Recommendation) is a communication tool recommended by the World Health Organization and the UK National Health Service. SBAR is a structured method for communicating critical information that requires immediate attention and action, contributing to effective escalation of management and increased patient safety. To our knowledge, this is the first study showing use of SBAR in South Africa (SA). OBJECTIVE: To determine the effectiveness of adopting the SBAR communication tool in an acute clinical setting in SA. METHODS: In the first phase of this study, neonatal nurses and doctors at Groote Schuur Hospital, Cape Town, were gathered in a focus group and given a questionnaire asking about communication in the neonatal department. Neonatal nurses and doctors were then trained to use SBAR. RESULTS: A telephone audit demonstrated an increase in SBAR use by registrars from 29% to 70% when calling consultants for help. After training, the majority of staff agreed that SBAR had helped with communication, confidence, and quality of patient care. There was qualitative evidence that SBAR led to greater promptness in care of acutely ill patients. CONCLUSIONS: Adopting SBAR was associated with perceived improvement in communication between professionals and in the quality and safety of patient care. It is suggested that this simple tool be introduced to many other hospitals in SA.

Resource implications of adopting a restrictive neonatal blood transfusion policy.

BACKGROUND: Blood transfusions (BTFs) are not without risk and pose a significant financial burden on resource-limited services. In line with current international evidence, the nursery at Groote Schuur Hospital (GSH), Cape Town, South Africa, introduced a restrictive BTF protocol to minimise transfusions and manage costs. OBJECTIVE: To determine whether adopting a restrictive BTF policy results in fewer transfusions. METHODS: Data were retrospectively collected on all infants who received BTFs in the GSH nursery over a 6-month period following adoption of a restrictive BTF policy in 2010. BTF figures for a similar time period before the restrictive policy, during 2008, were obtained for comparison. RESULTS: After introduction of the restrictive BTF policy, 42 of 1 097 infants admitted (3.8%) received a total of 64 BTFs. In comparison, 102 of a total of 940 infants (10.9%) admitted during a period of the same length before introduction of the restrictive BTF policy received a total of 121 transfusions. Comparison between the number of BTFs administered before and after the restrictive policy showed a highly statistically significant difference (p<0.001). The total cost of the blood products used in the two 6-month periods was R91 870 v. R48 640, based on current prices. CONCLUSIONS: By adopting a restrictive policy, we were able to halve the number of BTFs, reduce risks associated with transfusions, and achieve significant cost benefits. Following evidence-based guidelines results in high standards of care, while also making the most effective use of resources.

Enteral Feeding Practices in Preterm Infants in South Africa

Background. Optimal feeding regimens in babies weighing 1 000 g have not been established; and wide variations occur. In South Africa (SA) this situation is complicated by varied resource constraints.Objective. To determine the preterm enteral feeding practices of paediatricians in SA.Methods. We invited 288 paediatricians to participate in a cross-sectional web-based survey. Results. We received responses from 31.2 of the paediatricians; 43.6 were from the state sector and 56.4 from the private sector. Most participants worked in medium-sized neonatal units with 6 - 10 beds. The proportions commencing feeds within the first 24 hours were 24 in infants of 25 weeks' gestational age; 36 in infants 25 - 27 weeks; and 65 in infants 28 - 31 weeks. Feed volumes were routinely advanced daily in 47 of infants 25 weeks; 68 of infants 25 - 27 weeks; and 90 of infants 28 - 31 weeks. Forty-five per cent of infants 25 weeks received continuous intragastric feeds; while 50 of those in the 28 - 31 weeks group were on 3-hourly bolus feeds. The majority of the participants targeted full enteral feeds of 161 - 180 ml/kg/d; 66.7 had access to donor milk; and 77 used breastmilk fortifier.Conclusion. This is the first study to survey feeding practices in SA. The survey did not highlight differences in feeding practices among paediatricians. These data could be valuable in the design of local collaborative trials to determine optimal feeding strategies

A reduction of necrotising enterocolitis at Groote Schuur Hospital nursery.

Necrotising enterocolitis (NEC) is an gastro-intestinal emergency occurring almost solely in preterm, low birth weight infants. Mortality, morbidity and the complication rate are high. An increase in NEC at the Groote Schuur Hospital nursery in 2008 prompted a change of practice, resulting in a significant decrease in the condition.

Evaluating a simple method of neuroprotective hypothermia for newborn infants.

This study describes and evaluates a simple method of neuroprotective hypothermia for infants with hypoxic-ischaemic encephalopathy (HIE). Five term infants with HIE were cooled by applying soft, cold gel bags to the head. A radiant warmer, set to 34 degrees C, servo-controlled the temperature measured at a probe between the infant's back and the mattress. The infants' heads were shielded from the warmer. After 72 h, the infants were re-warmed by 0.2 degrees C per hour, by adjusting the radiant warmer. A rectal temperature of 34 degrees C was attained in a median time of 45 min. Mean rectal temperatures during cooling were 33.9 +/- 0.3 degrees C. There was good correlation between insulated back temperatures and deep rectal temperatures (r = 0.76). There were no major or irreversible adverse events during cooling. This method of cooling achieved rectal temperatures within the target range of 33-34 degrees C and re-warming was effective.

Xq28-linked noncompaction of the left ventricular myocardium: prenatal diagnosis and pathologic analysis of affected individuals.

Isolated noncompaction of the left ventricular myocardium (INVM) is characterized by the presence of numerous prominent trabeculations and deep intertrabecular recesses within the left ventricle, sometimes also affecting the right ventricle and interventricular septum. Familial occurrence of this disorder was described previously. We present a family in which 6 affected individuals demonstrated X-linked recessive inheritance of this trait. Affected relatives presented postnatally with left ventricular failure and arrhythmias, associated with the pathognomonic echocardiographic findings of INVM. The usual findings of Barth syndrome (neutropenia, growth retardation, elevated urinary organic acids, low carnitine levels, and mitochondrial abnormalities) were either absent or found inconsistently. Fetal echocardiograms obtained between 24-30 weeks of gestation in 3 of the affected males showed a dilated left ventricle in one heart, but were not otherwise diagnostic of INVM in any of the cases. Four of the affected individuals died during infancy, one is in cardiac failure at age 8 months, and one is alive following cardiac transplant at age 9 months. The hearts from infants who died or underwent transplantation appeared, on gross examination, to be enlarged, with coarse, deep ventricular trabeculations and prominent endocardial fibroelastosis. Histologically, there were loosely organized fascicles of myocytes in subepicardial and midmyocardial zones of both ventricles, and the myocytes showed thin, often angulated fibers with prominent central clearing and reduced numbers of filaments. Markedly elongated mitochondria were present in some ventricular myocytes from one specimen, but this finding was not reproducible. Genetic linkage analysis has localized INVM to the Xq28 region, where other myopathies with cardiac involvement have been located.

Very long chain acyl-CoA dehydrogenase deficiency: successful treatment of acute cardiomyopathy.

Very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is a severe defect of mitochondrial fatty acid oxidation characterized by hypertrophic cardiomyopathy, pericardial effusion, steatosis, and hypoglycemia, often resulting in death by 4-5 months of age. The onset of cardiomyopathy and pericardial effusion is insidious and sudden, necessitating early diagnosis and intervention to prevent death. A family affected with this defect is described in which dietary therapy with medium-chain triglycerides (MCT) was associated with rapid reversal of these severe clinical symptoms. Diagnosis by acylcarnitine analysis in the neonatal period can provide the opportunity for early clinical intervention. Prenatal diagnosis from amniocytes by enzymology or in vitro analysis of the fat oxidation pathway with deuterated fatty acid precursors has also been successful and permits intervention at birth. Of 10 affected children, 7 untreated cases died within the first several months while the remaining 3 cases survived when treated with medium-chain triglycerides as the major source of dietary fat.

The prevalence of women with breast implants in the United States--1989.

Most estimates of the number of women with breast implants appear to be extrapolations of industry or clinical data. While both provide valuable information, the former about the total number of devices ever produced or sold and the latter about the cumulative number of surgeries performed, neither can be used to directly estimate the prevalence of women with silicone gel or saline implants. In 1989, Market Facts, Inc., conducted a mail survey of 40,000 households chosen as representative of the population of the United States and received responses from 70.7%. Overall, the prevalence was 8.08 per 1,000 women with about 60% of the devices reportedly implanted for cosmetic reasons. The procedure was more common among Whites of the higher socio-economic classes. Based upon the results of this survey, the total number of US women in 1989 with breast implants was estimated to be 815,700 (95% confidence interval: 715,757-924,729).

The breast implant controversy.

The breast implant issue is a "bad news/good news" story. For many women with implants, the controversy has caused a fair degree of anxiety which may or may not be resolved as further information becomes available. It has also taken its toll on Dow Corning. Whole lines of medical products have been eliminated or are being phase out. The development of new medical applications has been terminated. As a consequence, employees have lost their jobs. What the effect will be on the biomedical industry as a whole remains to be seen (11). While silicones have been an important component in various medical devices, it is likely that other materials can be used as replacements. However, suppliers of non-silicone materials are also reevaluating their role in this market. For example, Du Pont, the nation's largest chemical company, has determined that the unpredictable and excessive costs of doing business with manufacturers of implantable medical devices no longer justifies the unrestricted sale of standard raw materials into this industry. Other companies are quietly following suit. On the up side, it is possible that the research being driven by this controversy will result in a greater understanding of the immunologic implications of xenobiotics, of the importance of nonbiased observations, of the need for ready access to valid data sets, and of the opportunity for valid scientific information to guide legal decisions. Only time will tell.

Randomized study assessing the effect of digoxin withdrawal in patients with mild to moderate chronic congestive heart failure: results of the PROVED trial. PROVED Investigative Group.

OBJECTIVES: The purpose of this study was to determine whether digoxin is effective in patients with chronic, stable mild to moderate heart failure. BACKGROUND: Digoxin has been a traditional therapy in heart failure, but methodologic limitations in earlier studies have prevented definitive conclusions regarding its efficacy. METHODS: Withdrawal of digoxin (placebo group, n = 46) or its continuation (digoxin group, n = 42) was performed in a prospective, randomized, double-blind, placebo-controlled multicenter trial of patients with chronic, stable mild to moderate heart failure secondary to left ventricular systolic dysfunction who had normal sinus rhythm and were receiving long-term treatment with diuretic drugs and digoxin. RESULTS: Patients withdrawn from digoxin therapy showed worsened maximal exercise capacity (median change in exercise time -96 s) compared with that of patients who continued to receive digoxin (change in exercise time +4.5 s) (p = 0.003). Patients withdrawn from digoxin therapy showed an increased incidence of treatment failures (p = 0.039) (39%, digoxin withdrawal group vs. 19%, digoxin maintenance group) and a decreased time to treatment failure (p = 0.037). In addition, patients who continued to receive digoxin had a lower body weight (p = 0.044) and heart rate (p = 0.003) and a higher left ventricular ejection fraction (p = 0.016). CONCLUSIONS: These data provide strong evidence of the clinical efficacy of digoxin in patients with normal sinus rhythm and mild to moderate chronic heart failure secondary to systolic dysfunction who are treated with diuretics.

Novel spirosuccinimides with incorporated isoindolone and benzisothiazole 1,1-dioxide moieties as aldose reductase inhibitors and antihyperglycemic agents.

Compounds from two novel series of spirosuccinimides were prepared. Analogs of series 2 possessed a spiro-fused isoindolone moiety while those of series 3 contained a spiro-fused benzisothiazole S,S-dioxide group. These compounds were evaluated as aldose reductase inhibitors (ARI) in vitro by their ability to inhibit glyceraldehyde reduction using a partially purified bovine lens aldose reductase preparation and in vivo as inhibitors of galactitol accumulation in the lens, sciatic nerve, and diaphragm of galactose-fed rats. Many members from the isoindolone series 2, particularly those containing an isoindolone N-methyl moiety, showed good in vitro and in vivo potency. The most potent member, the 6-chloro analog 32, was resolved, and aldose reductase activity was found to reside almost exclusively in the (+)-enantiomer. Compound 32 was approximately equipotent in the sciatic nerve of the galactose-fed rat to other cyclic imide ARI's of similar in vitro activity, namely sorbinil and ADN-138 and also to tolrestat, an acetic acid-based ARI (ED50's 4-8 mg/kg). Compounds from both series, 2 and 3, were also found to lower plasma glucose levels of genetically obese db/db and ob/ob mice with potency similar to that of ciglitazone. However, members from these series failed to lower insulin levels of the ob/ob mouse at the doses tested.