Emergence of enhanced attention to fearful faces between 5 and 7 months of age

The adult brain is endowed with mechanisms subserving enhanced processing of salient emotional and social cues. Stimuli associated with threat represent one such class of cues. Previous research suggests that preferential allocation of attention to social signals of threat (i.e. a preference for fearful over happy facial expressions) emerges during the second half of the first year. The present study was designed to determine the age of onset for infants’ attentional bias for fearful faces. Allocation of attention was studied by measuring event-related potentials (ERPs) and looking times (in a visual paired comparison task) to fearful and happy faces in 5- and 7-month-old infants. In 7-month-olds, the preferential allocation of attention to fearful faces was evident in both ERPs and looking times, i.e. the negative central mid-latency ERP amplitudes were more negative, and the looking times were longer for fearful than happy faces. No such differences were observed in the 5-month-olds. It is suggested that an enhanced sensitivity to facial signals of threat emerges between 5 and 7 months of age, and it may reflect functional development of the neural mechanisms involved in processing of emotionally significant stimuli.     

Plasmin and plasminogen activator activities in tear fluid during corneal wound healing after anterior keratectomy

Plasmin can degrade fibronectin and laminin, two important components of the extracellular matrix facilitating cell sliding and healing following a wound. In this study we investigated the relationship between the tear fluid level of plasmin and plasminogen activator and the healing of a corneal wound. Anterior keratectomy (AKE) was performed for seven rabbits (11 eyes). Eight eyes were rewounded after re-epithelialization. Tear fluid samples were collected with capillaries before wounding and during wound healing. Plasmin and plasminogen activator (PA) activities were determined using radial caseinolysis procedures. After AKE the plasmin concentrations increased rapidly, from a mean (+/- SEM) of 3.9 +/- 0.9 micrograms/ml to a mean of 37.9 +/- 7.8 micrograms/ml (p less than 0.01), and decreased during wound healing. Rewounding also resulted in an increase in plasmin concentration in the tear fluid (from a mean of 2.9 +/- 0.6 micrograms/ml to a mean of 5.0 +/- 1.1 micrograms/ml; p greater than 0.05). The PA activity showed an inverse trend as it decreased after AKE from a mean of 2.0 +/- 0.6 IU/ml to a mean of 0.3 +/- 0.1 IU/ml (p less than 0.001). During wound healing and re-epithelialization, the PA activity increased again, to 2.1 +/- 0.3 IU/ml (p less than 0.001). Abrasion of the newly grown epithelium in eight eyes caused a second elevation of PA activity which was not significant. This study demonstrates a close association between the healing of corneal wounds and changes in the plasmin and PA activities in tear fluid. Determination of the activity of these enzymes may therefore be useful for monitoring corneal wound healing.     

Operative treatment of pelvic apophyseal avulsions in adolescent and young adult athletes: a follow-up study

Introduction

Pelvic apophyseal avulsion can limit young athletes’ performance for months and may result in permanent disability. Nonoperative treatment is most commonly preferred, while surgical management with reduction and fixation is reserved for selected cases. Our aim was to evaluate outcomes of operative management of pelvic apophyseal avulsions in a series of adolescents and young adult athletes.

Materials and methods

Operative room registries and medical records were reviewed to identify patients who received surgical treatment for pelvic apophyseal avulsions who were younger than 24 years and with a minimum of 12 month follow-up.

Results

Thirty-two patients (16.8 years ± 2.6) were identified. The most common avulsion sites were anterior inferior iliac spine (34.4%, N = 11) and ischial tuberosity (34.4%, N = 11). Other avulsions were five cases (15.6%) of the pubic apophysis, four cases (12.5%) of the anterior superior iliac spine apophysis and one case of the iliac crest apophysis. Seventeen cases (53.1%) underwent surgery early, i.e., during the first 3 months after the acute injury. Twenty-two cases (68.8%) involved reduction with internal fixation, and six cases (18.8%) involved resection of the fragment. Twenty-six athletes (81.3%, N = 26) reported good outcomes and were able to return to preinjury sports level. Six patients (18.8%) had moderate outcome and reported activity limitations during high-level sports. Large displacement (> 20 mm) or delayed (> 3 months) surgery was not associated with inferior outcomes (P = 0.690 and P = 0.392, respectively). Injury side (P = 0.61) or gender (P = 0.345) did not affect outcomes.

Conclusions

Operative management of pelvic apophyseal avulsion results in return to the preinjury sports level in more than 80% of the cases. However, while both acute surgery for large displacement and delayed intervention for failed nonoperative treatment are generally successful in improving sports function in these cases, comparative studies are required to refine criteria for surgery.

Level of evidence

Case series, IV.

     

Beta-blockers, diuretics and physical fitness as determinants of serum lipids in myocardial infarction patients

Serum lipid levels were followed in myocardial infarction patients for one year after the infarction and related to their drug use and physical performance. Serum triglyceride concentrations were significantly elevated in patients using diuretics or diuretics and beta-blockers together both 3 and 12 months after the infarction when compared to patients not having drugs. The beta-blockers alone did not change triglycerides. No differences were found in total cholesterol concentration between any of the drug groups. The HDL cholesterol levels were significantly lower in all the drug groups 12 months after the infarction in comparison with the group using no drugs, but 3 months after the infarction these differences were not present. Total work in the exercise stress test correlated negatively with serum triglycerides and total cholesterol and positively with HDL/total cholesterol ratio in the group using no drugs 12 months after the infarction. In beta-blocker users, total work correlated negatively with triglyceride and total cholesterol concentrations. In all drug groups no correlation between total work and HDL/total cholesterol ratio could be found. These data suggest that despite differences in the physical working capacity between the groups, the drugs themselves are major determinants of differences in serum lipids.     

Prevalence and characteristics of pressure ulcers. A one-day patient population in a Finnish city

This article discusses the prevalence and characteristics of pressure ulcers in a one-day patient population in a Finnish city. The data was collected using two questionnaires. Data analysis was based on percentage distributions; statistical significances were tested with the Chi-square test. The measurement identified 186 patients with a total of 300 pressure ulcers. The majority (90%) of these patients were hospitalized and 10% were in outpatient care. The main causes for the development of pressure ulcers were inadequate turning and positioning and the patient's primary illness. Most of the ulcers were grade II. Only a few patients had ulcers that exposed bone. The preventive effort should extend from the nursing unit level, through the organizational level, to the level of society as a whole. It should consist of the identification of people at high risk for pressure ulcers and the provisions of quality care for these people.     

Role of pulmonary diseases and physical condition in the regulation of vasoactive hormones

Summary. Lungs have many non-respiratory metabolic functions, of which some take place in the capillary endothelium, while others are in parenchymal lung tissue. We have studied the role of the lungs in the metabolism of vasoactive and some other hormones by comparing patients who have undergone lung resection to those having various obstructive or fibrotic lung diseases. We have also compared these groups with persons in good physical health. The data suggested that lung resection patients had low angiotensin II levels in plasma but the response of angiotensin II to exercise was normal. Also adrenalin concentration was low in the lung resection group while dopamine did not show any significant difference between the groups. When hormone levels were correlated to the exercise data, renin levels were especially related to physical condition. Serum post-exercise renin values were inversely related to the uneven distribution of lung perfusion, possibly thus reflecting the diminished pulmonary vascularization. A negative association was found between angiotensin II and diffusion capacity. Thus, the angiotensin II levels may preferably be controlled by the non-circulatory functions of the lungs.     

Prenatal Origins of Poor Sleep in Children

Study Objectives:

We examined whether small body size at birth and prenatal tobacco or alcohol exposure predict poor sleep and more sleep disturbances in children.

Design:

An epidemiologic cohort study of 289 eight-year-old children born at term.

Measurements and results:

Sleep duration and efficiency were measured by actigraphy for 7 consecutive nights (mean = 7.1, SD = 1.2). We used both continuous measures of poor sleep and binary variables of short sleep and low sleep efficiency ( ≤ 10^th percentiles). Parents completed the Sleep Disturbance Scale for Children. Lower birth weight and shorter length at birth were associated with lower sleep efficiency. For every 1-SD decrease in weight and length at birth, the odds for low sleep efficiency increased by 1.7 fold (95% confidence interval [CI]: 1.1 to 2.7) and 2.2 fold (95% CI: 1.3 to 3.7), respectively. For every 1-SD decrease in ponderal index at birth, the risk of parent-reported sleep disorders increased by 1.4 fold (95% CI: 1.0 to 2.0). Moreover, children exposed prenatally to alcohol had a 2.9-fold (95% CI: 1.1 to 7.6) and 3.6-fold (95% CI: 1.3 to 10.0) increased risk for having short sleep and low sleep efficiency, respectively. The associations were not confounded by sex, gestational length, prenatal and perinatal complications, body mass index at 8 years, asthma, allergies, or parental socioeconomic status.

Conclusions:

Poor sleep in children may have prenatal origins. Possible mechanisms include alcohol consumption during pregnancy and other conditions associated with small body size at birth.

Citation:

Pesonen AK; Röaikköonen K; Matthews K; Heinonen K; Paavonen JE; Lahti J; Komsi N; Lemola S; Jöarvenpöaöa AL; Kajantie E; Strandberg T. Prenatal origins of poor sleep in children. SLEEP 2009;32(8):1086-1092.     

Loa loa Microfilariae Evade Complement Attack In Vivo by Acquiring Regulatory Proteins from Host Plasma

Loa loa is a filarial nematode that infects humans. The adults live in subcutaneous tissues and produce microfilariae that live for several weeks in the blood circulation in order to be transmitted to another person via blood meals of a dipterian vector. As microfilariae live in continuous contact with plasma, it is obvious that they evade the complement system. We studied markers of complement activation and signs of complement regulation on Loa loa microfilariae in vivo. The microfilariae were isolated from anticoagulated blood samples of a Loa loa-infected Caucasian patient. C1q and some mannose-binding lectin but only a limited amount of C3b or C4b fragments and practically no C5 or C5b-9 were present on the microfilariae. The covalently microfilaria-bound C3 and C4 depositions were mainly inactive iC3b, C3c, and iC4b fragments indicating that microfilariae had regulated complement activation in vivo. Also, in vitro deposition of C3b onto the microfilariae upon serum exposure was limited. The patient-isolated microfilariae were found to carry the host complement regulators factor H and C4b-binding protein on the outermost layer, so called sheath. The microfilaria-bound factor H was functionally active. Binding of the complement regulators to the microfilariae was confirmed in vitro using ¹²⁵I-labeled factor H and C4b-binding protein. In conclusion, our study shows that Loa loa microfilariae block complement activation and acquire the host complement regulators factor H and C4b-binding protein in blood circulation. This is the first time that binding of complement regulators onto nonviral pathogens has been demonstrated to occur in humans in vivo.Loa loa is a filarial parasite and the causative agent of human loiasis. This nematode has adapted well to its human host, as the adults can migrate in subcutaneous tissues for at least 15 years (15). During its whole adult life this helminth can produce microfilariae (MF) in peripheral blood, and these can circulate in blood for several weeks before transmission to the vector. Loiasis is transmitted by a dipteran vector (Chrysops spp.). The infective larvae can enter human subcutaneous tissues through a bite wound when the vector feeds again after the first blood meal. The larvae develop into adults and mate in subcutaneous tissues, resulting in production of sheathed MF after a minimum of 5 months. The MF are found mainly in peripheral blood (34).The prevalence of loiasis is high in the regions of endemicity in western and central Africa, where 20 to 40% of the population is microfilaremic (10). The majority of the infected individuals are asymptomatic, but a significant proportion of patients have symptoms such as calabar swellings, pruritis, secondary dermal lesions, and a subconjunctival eye passage of the adult worm (33, 37). In addition, serious sequelae such as endomyocardial fibrosis, renal complications, and encephalitis have also been reported (1).The main functions of the complement system are to eliminate foreign organisms that come in contact with plasma or other body fluids, either by direct effects or by enhancement of the acquired humoral immune response. Depending on the activator, complement can be activated through three pathways: the classical pathway (CP), the alternative pathway (AP), and the lectin pathway (LP). Upon activation, these pathways lead to the terminal pathway and formation of membrane attack complexes on the target cell (31).Complement activation is regulated by a variety of complement regulatory proteins. Most of the regulators are membrane bound, while two major regulators, complement factor H (CFH) and C4b-binding protein (C4BP), are plasma proteins found in high concentrations (12, 17, 47). All the three pathways lead to activation of C3, the central molecule of the complement cascade (8). Activation of C3 to C3b results in release of an anaphylatoxin, C3a (20, 21), while the C3b fragment can attach covalently to the target surface to start the AP amplification or to promote activation of the CP or LP (32). Inactivation of C3b to inactive C3b (iC3b) is carried out by serine protease factor I (FI), which needs a cofactor such as CFH (6, 8). In addition to the cofactor activity, CFH can also downregulate generation of C3b by two other means (11, 46).In the CP and LP, activation of the component C4 is essential. Upon activation, C4b is attached covalently to the target surface (27, 45) and can form an active C3-convertase, C4b2a, which is essential for propagation of the CP and LP (5). This step is regulated in plasma by complement regulatory protein C4BP, which acts as a cofactor for FI in degradation of C4b to inactive C4b (iC4b) or as an accelerator of the decay of C4b2a (23, 40, 44).Since MF of Loa loa are able to live and migrate in blood for weeks, they are obviously able to resist elimination by complement, but the mechanisms are largely unknown. One immune evasion mechanism of Loa loa is known to be induction of T-cell anergy (25), but nothing is known about evasion of innate or humoral immunity. A few complement resistance mechanisms have been reported for other helminths. Most of these are associated with physical barriers of macroscopic worms, but some helminths are known to have specific molecules mediating complement evasion or ligands that acquire host complement regulators on their surfaces (22). So far, two human helminth parasite structures have been shown to acquire host CFH on their surfaces, the echinococcal cyst wall and MF of a filarial nematode, Onchocerca volvulus (7, 30). So far there are no reports of acquisition of C4BP onto any pathogenic helminth. Several pathogenic bacteria and yeasts and a few viruses are known to utilize acquisition of host CFH or C4BP to evade complement attack (49). Four of these microbes, Streptococcus pyogenes, Borrelia burgdorferi, relapsing fever Borrelia, and Candida albicans, can acquire both CFH and C4BP on their surface (3, 28, 29). So far, all the reports where CFH or C4BP acquisition on microbes has been reported have been based on in vitro experiments only.The aim of our study was to analyze whether patient-derived Loa loa MF carry any markers of complement attack or signs of cessation of the complement cascade. The MF showed C1q deposits, as was expected since the patient had antifilarial antibodies. Despite that, however, only limited amounts of C3 or C4 fragments and practically no C5 or C5b-9 could be detected on MF. The covalently bound C3 or C4 fragments were mainly iC3b, C3c, or iC4b. Most importantly we show that MF had acquired CFH and C4BP on their surfaces in vivo. In conclusion, for the first time we show acquisition of soluble complement regulators on pathogenic microbes in the human body. Our results suggest that acquisition of complement regulators CFH and C4BP from human plasma on MF could at least partially explain the prolonged survival of MF in circulation.