An Investigation of the Relationship Between the Second-to-Fourth Digit Ratio and Sagittal Synostosis.

BACKGROUND: The most common presentation of nonsyndromic craniosynostosis is that of the sagittal suture. Amongst this subgroup there is a significant male preponderance. Although the etiology is largely unknown, androgen exposure in utero has been suggested as a contributing factor. The second-to-fourth digit ratio (2D:4D) is a sexually dimorphic trait, reflective of the levels of androgen and estrogen exposure in utero, with a lower 2D:4D ratio associated with higher androgen exposure.This study aimed to examine the difference in 2D:4D ratio between participants with sagittal synostosis (SS) and gender- matched controls, hypothesizing that alterations in androgen exposure would be reflected in participants' 2D:4D ratio. METHOD: Participants with nonsyndromic SS and gender-matched controls were prospectively recruited from outpatients clinics. Photographs were taken of the right hand, and 3 independent researchers measured the length of the fingers and 2D:4D ratio, with the mean 2D:4D ratio then calculated. RESULTS: Fifty-six participants were recruited to both groups, with 35 males and 21 females in each. The mean age of the study and control groups were 5.6 and 6.3 years, respectively. There was no difference in the 2D:4D ratio between groups overall ( P = 0.126). However, males with SS had a significantly higher 2D:4D ratio in comparison to male controls (0.969 ± 0.379 versus 0.950 ± 0.354, P = 0.038). CONCLUSIONS: Our results suggest that 1 single hormonal pathway is not responsible for suture fusion. Subsequently we consider that an imbalance between testosterone and estrogen signaling may contribute to the development of sagittal craniosynostosis.

Risk factors for the occurrence of Escherichia coli virulence genes eae, stx1 and stx2 in wild bird populations.

Shiga toxin-producing Escherichia coli (STEC) can cause serious disease in human beings. Ruminants are considered to be the main reservoir of human STEC infections. However, STEC have also been isolated from other domestic animals, wild mammals and birds. We describe a cross-sectional study of wild birds in northern England to determine the prevalence of E. coli-containing genes that encode Shiga toxins (stx1 and stx2) and intimin (eae), important virulence determinants of STEC associated with human disease. Multivariable logistic regression analysis identified unique risk factors for the occurrence of each virulence gene in wild bird populations. The results of our study indicate that while wild birds are unlikely to be direct sources of STEC infections, they do represent a potential reservoir of virulence genes. This, coupled with their ability to act as long-distance vectors of STEC, means that wild birds have the potential to influence the spread and evolution of STEC.

New and underutilised technologies to reduce maternal mortality and morbidity: what progress have we made since Bellagio 2003?

In 2003, maternal health experts met in Bellagio, to consider new and underutilised technologies vital to pregnancy-related health services in low-resource settings. Five years later, we examine what progress has been made and what new opportunities may be on the horizon. Based on a review of literature and consultation with experts, we consider technologies addressing the five leading causes of maternal mortality: postpartum haemorrhage, eclampsia, obstructed labour, puerperal sepsis, and unsafe abortion (pregnancy termination and miscarriage). In addition, we consider technologies related to obstetric fistula, which has received more attention in recent years.

Long-term preservation of cortically dependent visual function in RCS rats by transplantation.

Cell transplantation is one way of limiting the progress of retinal degeneration in animal models of blinding diseases such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD). Here we transplanted a human retinal pigment epithelial (RPE) cell line into the subretinal space of one such model, the Royal College of Surgeons (RCS) rat, and showed, using head tracking to moving stripes and pattern discrimination in conjunction with single-unit cortical physiology, that cortically mediated vision can be preserved with this treatment.

Equestrian Injury Presentations to a Regional Trauma Centre in Ireland.

Background: The Irish Equestrian industry provides over 12,500 full time job equivalents contributing in excess of €454 million to the Irish economy annually. For such an important industry there is a paucity of information relating to equestrian injuries. Aims: The aim of this study was to determine the demographics, characteristics, and outcomes of equestrian related injuries presenting to the emergency department of a regional trauma centre in Ireland over the course of one year. Methods: Retrospective analysis of all 30,700 presentations to the emergency department (ED) of the Midland Regional Hospital (MRH) Tullamore in 2013 was performed to identify equestrian related presentations. Patient demographics, mechanism of injury, radiology results, management, and follow-up data were collected and analysed using Microsoft Excel software. Results: A total of 149 equestrian related presentations were identified during the study period. There were significantly more females involved in equestrian injuries than males (58% versus 42%). Falling from a horse contributed to significantly more presentations and admissions than any other cause. 36% of presentations were associated with a radiological abnormality. Types of injuries identified included skeletal fractures (27.5%), joint dislocation/subluxation (5%), concussion (12.5%), and splenic laceration/intraperitoneal haemorrhage (1%). Admission or transfer to tertiary care was required for 18% of equestrian injuries. Only 43% of presentations were discharged back to primary care from the emergency department. Conclusion: This study identifies a high incidence of morbidities associated with equestrian presentations. In addition we recognised populations at risk of specific injuries and described high-risk mechanisms of injury.

Constant illumination causes spatially discrete dopamine depletion in the normal and degenerate retina.

A fully competent retinal dopamine system underpins normal visual function. Although this system is known to be compromised both prior to and during retinal degeneration, the spatial dynamics of dopamine turnover within the degenerate retina are at present unknown. Here, using immunohistochemistry for dopamine in combination with quantitative optical density measurements, we reveal a global decline in retinal dopamine levels in the light adapted RCS dystrophic rat, which is restricted to plexiform layers in the dark. Pharmacological blockade of dopamine production with the drug alpha-methyl-p-tyrosine (AMPT) allows the direct visualisation of dopamine depletion in normal and degenerate retina in response to constant illumination. In normal retinae this effect is spatially discrete, being undetectable in perikarya and specific to amacrine cell fibres in sublamina 1 of the inner plexiform layer. A similar response was observed in the retinae of dystrophic rats but with a reduction in amplitude of approximately 50%. It is suggested that the pattern of dopamine depletion observed in rat retina may reflect an AMPT-resistant pool of perikaryal dopamine and/or a reduction in extrasynaptic release of this neurotransmitter in response to illumination in vivo. We conclude that the visualisation of dopamine depletion reported here represents a release of this neurotransmitter in the response to light. Turnover of dopamine in the dystrophic retina is discussed in the context of surviving photoreceptors, including the intrinsically photosensitive melanopsin ganglion cells of the inner retina.

Validation of accuracy and community acceptance of the BIRTHweigh III scale for categorizing newborn weight in rural India.

OBJECTIVE: To determine the accuracy and acceptability of a handheld scale prototype designed for nonliterate users to classify newborns into three weight categories (>or=2,500 g; 2,000 to 2,499 g; and <2,000 g). STUDY DESIGN: Weights of 1,100 newborns in Uttar Pradesh, India, were measured on the test scale and validated against a gold standard. Mothers, family members and community health stakeholders were interviewed to assess the acceptability of the test scale. RESULT: The test scale was highly sensitive and specific at classifying newborn weight (normal weight: 95.3 and 96.3%, respectively; low birth weight: 90.4 and 99.2%, respectively; very low birth weight: 91.7 and 98.4%, respectively). It was the overall agreement of the community that the test scale was more practical and easier to interpret than the gold standard. CONCLUSION: The BIRTHweigh III scale accurately identifies low birth weight and very low birth weight newborns to target weight-specific interventions. The scale is extremely practical and useful for resource-poor settings, especially those with low levels of literacy.

A retrospective review of farm injuries presenting to an Irish hospital emergency department in 2013.

BACKGROUND: The agricultural and equestrian businesses are an important source of employment in the Midlands. This is a retrospective study examining the demographics, characteristics, and outcomes of agricultural and equestrian related injuries presenting to the Midland Regional Hospital, Tullamore, Co. Offaly. There were a total of 30,700 attendances to the Emergency Department for 2013. AIMS: This study is an epidemiological review of agricultural injuries, their mechanisms, and consequences presenting to a rural regional hospital over a 1 year period. METHODS: Every presentation to the Accident and Emergency Department at the Midlands Regional Hospital in 2013 was assessed retrospectively to determine if an injury had been sustained in an agricultural environment. Patient demographics, month of occurrence, mechanism of injury, radiology results, management, and follow-up data were collected and analysed using Microsoft Excel. RESULTS: There were 144 agricultural-related presentations to the Accident and Emergency Department. 23% of the agricultural injuries were identified as having a radiological abnormality. There were significantly more males involved in agricultural injuries than females (97 vs 3%). 16% of presentations required admission or transfer to tertiary specialist care and 8% required surgical intervention. Farming machinery accidents contributed to more admissions than any other cause in the agricultural category and resulted in more surgical interventions. CONCLUSION: Our study has identified high-risk mechanisms of injury, which should alert clinicians to the potential for significant injury. In addition, our findings could be used to help policy makers promote safety and awareness through public health policies that target high-risk practices with appropriate training and legislation.

The impact of intracerebral retinal transplants on types of behavior exhibited by host rats.

Retinae transplanted over the midbrain of newborn rats establish functional connections with host brain centers, which provide a substrate for several distinct visual functions. These responses provide insight into the relationship between anatomy and behavior under normal conditions and after brain injury, as well as into the strategies used by an animal to extract significant information from its visual environment.

Cell transplantation as a treatment for retinal disease.

It has been shown that photoreceptor degeneration can be limited in experimental animals by transplantation of fresh RPE to the subretinal space. There is also evidence that retinal cell transplants can be used to reconstruct retinal circuitry in dystrophic animals. Here we describe and review recent developments that highlight the necessary steps that should be taken prior to embarking on clinical trials in humans.

Involving the community in cervical cancer prevention programs.

Underutilization of cervical cancer prevention services by women in the high-risk age group of 30-60 years can be attributed to health service factors (such as poor availability, poor accessibility, and poor quality of care provided), to women's lack of information, and to cultural and behavioral barriers. The Alliance for Cervical Cancer Prevention (ACCP) partners have been working to identify effective ways to increase women's voluntary participation in prevention programs by testing strategies of community involvement in developing countries. The ACCP experiences include developing community partnerships to listen to and learn from the community, thereby enhancing appropriateness of services; developing culturally appropriate messages and educational materials; making access to high-quality screening services easier; and identifying effective ways to encourage women and their partners to complete diagnosis and treatment regimens. Cervical cancer prevention programs that use these strategies are more likely to increase demand, ensure follow-through for treatment, and ultimately reduce disease burden.

A role for the outer retina in development of the intrinsic pupillary light reflex in mice.

Mice do not require the brain in order to maintain constricted pupils. However, little is known about this intrinsic pupillary light reflex (iPLR) beyond a requirement for melanopsin in the iris and an intact retinal ciliary marginal zone (CMZ). Here, we study the mouse iPLR in vitro and examine a potential role for outer retina (rods and cones) in this response. In wild-type mice the iPLR was absent at postnatal day 17 (P17), developing progressively from P21-P49. However, the iPLR only achieved ∼ 30% of the wild-type constriction in adult mice with severe outer retinal degeneration (rd and rdcl). Paradoxically, the iPLR increased significantly in retinal degenerate mice >1.5 years of age. This was accompanied by an increase in baseline pupil tone in the dark to levels indistinguishable from those in adult wild types. This rejuvenated iPLR response was slowed by atropine application, suggesting the involvement of cholinergic neurotransmission. We could find no evidence of an increase in melanopsin expression by quantitative PCR in the iris and ciliary body of aged retinal degenerates and a detailed anatomical analysis revealed a significant decline in melanopsin-positive intrinsically photosensitive retinal ganglion cells (ipRGCs) in rdcl mice >1.5 years. Adult mice lacking rod function (Gnat1(-/-)) also had a weak iPLR, while mice lacking functional cones (Cpfl5) maintained a robust response. We also identify an important role for pigmentation in the development of the mouse iPLR, with only a weak and transient response present in albino animals. Our results show that the iPLR in mice develops unexpectedly late and are consistent with a role for rods and pigmentation in the development of this response in mice. The enhancement of the iPLR in aged degenerate mice was extremely surprising but may have relevance to behavioral observations in mice and patients with retinitis pigmentosa.

Face processing impairments after encephalitis: amygdala damage and recognition of fear.

Face processing and facial emotion recognition were investigated in five post-encephalitic people of average or above-average intelligence. Four of these people (JC, YW, RB and SE) had extensive damage in the region of the amygdala. A fifth post-encephalitic person with predominantly hippocampal damage and relative sparing of the amygdala (RS) participated, allowing us to contrast the effects of temporal lobe damage including and excluding the amygdala region. The findings showed impaired recognition of fear following bilateral temporal lobe damage when this included the amygdala. For JC, this was part of a constellation of deficits on face processing tasks, with impaired recognition of several emotions. SE, YW and RB, however, showed relatively circumscribed deficits. Although they all had some problems in recognizing or naming famous faces, and had poor memory for faces on the Warrington Recognition Memory Test, none showed a significant impairment on the Benton Test of Facial Recognition, indicating relatively good perception of the face's physical structure. In a test of recognition of basic emotions (happiness, surprise, fear, sadness, disgust and anger), SE, YW and RB achieved normal levels of performance in comparison to our control group for all emotions except fear. Their results contrast with those of RS, with relative sparing of the amygdala region and unimpaired recognition of emotion, pointing clearly toward the importance of the amygdala in the recognition of fear.

Basal increase in c-Fos-like expression in superior colliculus of Royal College of Surgeons dystrophic rats can be abolished by intraocular injection of tetrodotoxin.

In normal rats maintained in the dark, very few cells in the primary visual centers, including the superior colliculus, show Fos-like immunoreactivity. By contrast, in rats presented with flashing lights many Fos-like immunoreactivity cells are observed distributed throughout the visual centers. In the dystrophic Royal College of Surgeons rat, in which there is major loss of photoreceptors over the first 3 months of life, similar numbers of Fos-like immunoreactivity cells are seen on light presentation, but in marked contrast, cell densities in the rats maintained in the dark are many times higher than in non-dystrophic rats maintained under similar conditions. Here we show that this elevated dark response can be abolished by intravitreal injection of the sodium channel blocker tetrodotoxin, indicating that this effect results from changed retinal activity, rather than being centrally generated. We suggest that since Fos-like immunoreactivity is not usually elicited by steady state conditions, the elevated levels in the superior colliculus in these animals reflect the return of waves of activity, first seen in development coursing across the retina, but lost with photoreceptor maturation.

An investigation into the early stages of the inflammatory response following ibotenic acid-induced neuronal degeneration.

Injection of the excitatory neurotoxin ibotenic acid into the septum produces rapid destruction of neuronal cell bodies and accompanying gliosis. We have previously shown that following ibotenate-induced cell death this may also result in damage to healthy axons en passage (Coffey et al., Neurosci. Lett. 84, 178-184, 1988). We suggested that the axonal damage resulted from non-specific damage by recruited inflammatory cells. In this study we have further examined the phenotype of the cells involved in the inflammatory response in the rat. Immunocytochemical identification of cells in the region of the lesion site identifies them as being of haematopoitic origin and most of them have the phenotype of macrophages. The dramatic increase in their number following an ibotenate lesion is sensitive to irradiation of the body providing evidence that the majority are blood derived. The inflammatory response is accompanied by a loss of myelin and a breakdown of the blood-brain barrier in the region of the lesion site. We have shown that these two effects are consequences of the inflammatory response since reduction in the inflammatory response by prior irradiation will abrogate these two effects.

Sensory capacity of the royal college of surgeons rat.

PURPOSE: To apply noninvasive tests for examining visual and other sensory functions of pigmented Royal College of Surgeons (RCS) rats compared with pigmented and albino control animals. METHODS: Rats aged 3 and 7 months were tested with a general neurologic examination that assessed visual, auditory, tactile, and whisker displacement responses. Photophobic responses and visual discrimination were also measured. RESULTS: Dystrophic RCS rats failed the visual presentation tests, even at 3 months of age, and showed diminished performance on tactile tests. Auditory and whisker displacement performances were normal. Albino rats also showed diminished performance on the visual test, particularly to stimuli presented in the upper visual field. Photophobic responses were diminished in the dystrophic RCS rats compared with the pigmented control animals. Albino animals showed heightened photophobia. The dystrophic rats failed to reach criterion levels of performance on the visual discrimination test even with gratings of 0.045 cyc/deg. CONCLUSIONS: The tests used discriminate deteriorated complex visual functions in RCS rats at ages when some simple reflexes can still be demonstrated. As such, they provide easily executed tests for screening for the effects of reparative treatments such as transplantation, administration of growth factors, and gene transfer technology. The integrity of whisker and auditory function are important when using tests requiring polysensory inputs. The somatosensory defect is surprising but may be useful in searching for the gene locus of the retinal disorder. The aberrations seen in the albino rats may be attributable to the effects of light damage and unfiltered light.

Schwann cell grafting into the retina of the dystrophic RCS rat limits functional deterioration. Royal College of Surgeons.

PURPOSE: To examine whether congenic Schwann cells grafted into the subretinal space of dystrophic Royal College of Surgeons (RCS) rats can prevent photoreceptor loss and maintain visual function. METHODS: Purified neonatal Schwann cells derived from congenic rats were grafted into the subretinal space of 3- to 4-week-old dystrophic RCS rats. Graft placement was confirmed using Schwann cells labeled in vitro with the fluorescent dye Hoechst 33342 or in grafted eyes processed for electron microscopy (48-hour to 1-month survival). At longer intervals, up to 9 months after surgery, animals were examined for photoreceptor survival; preservation of a visual reflex, head-tracking to moving stripes; and preservation of visual receptive fields associated with the region of graft placement. RESULTS: One week after the graft was performed, Schwann cells had integrated into the subretinal space with little evidence of a reactive response. When screened for head-tracking to moving stripes, Schwann cell-grafted animals performed better than sham-treated or control dystrophic animals. Threshold sensitivity measurements and visual field assessment made by recording from the superior colliculus also showed a significant level of preserved function compared with control animals. Functional rescue was correlated with photoreceptor survival and could be observed for at least 9 months after grafting. CONCLUSIONS: Schwann cells injected into the subretinal space limit functional deterioration and prolong photoreceptor survival. It is suggested that they act by local release of growth factors that either support photoreceptors directly and/or stimulate phagocytosis in RPE cells.

Pseudo-random procedures for rapid presentation rates using optical imaging and spectroscopy.

Optical imaging of rat barrel cortex has provided detailed spatio-temporal maps of functional cortical architecture. We describe an event-related procedure (ERP) for optical imaging based on selective signal averaging as reported by Burock et al., using an anti-correlative pseudo-random event sequence. The sequence used 1 s vibrissal stimulation at 5 Hz, with an interevent interval of 2 s. This rapid presentation rate allows for greater statistical power per unit time, and allows for direct comparison of event-related studies with other imaging modalities. The spatio-temporal characteristics of single wavelength and spectrographic results were found to be comparable with those obtained by standard techniques, although a general lessening of haemodynamic response function (HRF) was noted. We also describe a method of locating barrel activity by spectral analysis of summed event data. Using this technique, the power spectrum of remitted light from the barrel region was found to peak within +/- 0.12 Hz of the inter-event interval frequency.

beta-peptides as catalysts: poly-beta-leucine as a catalyst for the Juliá-Colonna asymmetric epoxidation of enones.

Poly-beta-leucines have been evaluated as catalysts for the Juliá-Colonna asymmetric epoxidation of enones; the beta 3-isomer was found to be an effective catalyst for the epoxidation of chalcone (70% ee) and some analogues.

Prepulse facilitation of auditory startle response in hamsters.

A visual prepulse was applied just before a burst of white noise with various lead intervals ranging from 50 to 400 ms in hamsters. After habituation each hamster received 120 trials of the auditory noise with or without the prepulse. Amplitude of startle response increased significantly at 100 ms and 200 ms (n = 10). This enhancement disappeared in blind controls (n = 6). The amplitude of startle response decreased during exploratory behavior, grooming, sniffing or other movements. However, the facilitatory effects of the visual prepulse were consistent, regardless of the animal's behavioral states, except sniffing. The authors conclude that visual prepulse task is useful for studying the ability to detect visual signals in hamsters, and that further study is necessary to elucidate the factors affecting the enhancement of startle response in hamsters.