Bayesian QTL analyses using pedigreed families of an outcrossing species, with application to fruit firmness in apple.

KEY MESSAGE: Proof of concept of Bayesian integrated QTL analyses across pedigree-related families from breeding programs of an outbreeding species. Results include QTL confidence intervals, individuals' genotype probabilities and genomic breeding values. Bayesian QTL linkage mapping approaches offer the flexibility to study multiple full sib families with known pedigrees simultaneously. Such a joint analysis increases the probability of detecting these quantitative trait loci (QTL) and provide insight of the magnitude of QTL across different genetic backgrounds. Here, we present an improved Bayesian multi-QTL pedigree-based approach on an outcrossing species using progenies with different (complex) genetic relationships. Different modeling assumptions were studied in the QTL analyses, i.e., the a priori expected number of QTL varied and polygenic effects were considered. The inferences include number of QTL, additive QTL effect sizes and supporting credible intervals, posterior probabilities of QTL genotypes for all individuals in the dataset, and QTL-based as well as genome-wide breeding values. All these features have been implemented in the FlexQTL(™) software. We analyzed fruit firmness in a large apple dataset that comprised 1,347 individuals forming 27 full sib families and their known ancestral pedigrees, with genotypes for 87 SSR markers on 17 chromosomes. We report strong or positive evidence for 14 QTL for fruit firmness on eight chromosomes, validating our approach as several of these QTL were reported previously, though dispersed over a series of studies based on single mapping populations. Interpretation of linked QTL was possible via individuals' QTL genotypes. The correlation between the genomic breeding values and phenotypes was on average 90 %, but varied with the number of detected QTL in a family. The detailed posterior knowledge on QTL of potential parents is critical for the efficiency of marker-assisted breeding.

The investigation of congenital infection by Trypanosoma cruzi in an endemic area of Chile: three protocols explored in a pilot project.

Given the increasing travel of pregnant women from areas were Trypanosoma cruzi is endemic, the congenital transmission of the parasite has become a global public-health problem. In a recent pilot study, which ran in Chile from 2006 to 2010, three strategies for exploring and managing T. cruzi-infected mothers and their infected or uninfected neonates were investigated. Any protocols applied to the investigation of such mother-and-child pairs need to include the detection of infection in pregnant women, the detection of infection, if any, in the children born to the women, the appropriate treatment of the infected neonates, and the serological-parasitological follow-up of all of the neonates until their medical discharge.

Apple and peach consumption habits across European countries.

The aim of this study was to gain information concerning apple and peach consumption frequency within different European countries in relation to age and gender. The survey was a part of a complex experiment with the aim of evaluating consumers' preferences towards new varieties, and the data is based on the self-reported declarations of respondents, male and female, between 15 and 70 years old. 4271 consumers from 7 European countries were invited to supply information about their apple consumption habits, whereas 499 respondents from 5 countries answered questions relating to frequency of peach and nectarine consumption. In both, the apple and the peach surveys, data analysis of declared intake showed significant differences between nationalities. The highest apple consumption was in Poland, where over 55% declared a consumption of more than 5 apples per week. In comparison, Italian consumers most often indicated eating 3-5 apples per week (39.3%). The lowest apple consumption was in the Netherlands and Spain. In the case of peaches, the highest consumption was indicated in France where 48% of respondents declared a peach consumption of 3-5 per week with 40% eating more than 5 fruits per week. The lowest peach intake was declared in Germany. Irrespective of country women were shown to eat more apples that men. Furthermore, the group of older people (61-70 years) consume apples more often than the adult group (36-60), while within the youngest group of consumers (16-35) eating apples was not at all popular. As with apples females declared a higher peach consumption, and again significantly lower fruit consumption by the youngest group (16-35) was indicated. Although the availability of fruit at the market remains a prime factor in determining apple and peach consumption, our survey confirmed the trends of declining this popular fruit intake by the younger generation, as well as the persistent tendency of lower frequency of fruit consumption among men than women.

Multiple sulfatase deficiency: clinical, neuropathological, ultrastructural and biochemical studies.

We describe the clinical, pathological, ultrastructural and biochemical features in the case of a 15-year-old boy with multiple sulfatase deficiency. Clinical abnormalities included hypotonia, retarded psychomotor development, hepatosplenomegaly, pigmentary degeneration of the retina, myoclonic seizures, aortic insufficiency and quadriplegia. Urinalysis revealed increased heparan sulfate. At necropsy, aortic and mitral valves revealed nodular thickening and periodic acid-Schiff (PAS)-positive, metachromatic granules in renal proximal tubules. The brain weighed 400 g and demonstrated cerebral and cerebellar atrophy with a retrocerebellar meningeal cyst. Cortical neurons contained periodic acid-Schiff-positive and cresyl violet-reactive granules. White matter demonstrated brown metachromasia and intense fibrillary gliosis. Conjunctival fibroblasts contained amorphous vacuoles with dense osmiophilic nucleoid cores. Pleomorphic extracellular, intraneural and intraglial inclusions were noted in the brain. Activities of arylsulfatase A, B and C were diminished markedly in autopsied tissue from brain, liver, and kidney (0, 0 and less than 10% of control activities, respectively). Partial deficiencies of iduronate sulfatase and heparan sulfatase were noted in different tissues. Variable decreased enzyme activities were expressed in leukocytes: arylsulfatase A, less than 33%; B, 40%; and C, 90%; heparan sulfatase, 2%; and iduronate sulfatase was not detectable. Near normal activities were found in cultured fibroblasts.

Surgical decompression for traumatic brain swelling: indications and results.

OBJECT: Decompressive craniectomy has been performed since 1977 in patients with traumatic brain injury. The authors assess the efficacy of this treatment and the indications for its use. METHODS: The clinical status of the 57 patients, their computerized tomography (CT) scans, and intracranial pressure (ICP) levels were documented prospectively in a standard protocol. At the beginning of the study, all patients older than 30 years were excluded. As of 1989 patients older than 40 years were excluded until 1991; since that time patients older than 50 years have been excluded. Primary brain or brainstem injury with fully developed bulbar brain syndrome, loss of auditory evoked potentials (AEPs), and/or oscillation flow in a transcranial Doppler ultrasound examination were contraindications to decompressive craniectomy. A positive indication for decompression was given in the case of progressive therapy-resistant intracranial hypertension in correlation with clinical (Glasgow Coma Scale [GCS] score, decerebrate posturing, dilating of pupils) and electrophysiological (electroencephalography, somatosensory evoked potentials, and AEPs) parameters and with findings on CT scans. Unilateral decompressive craniectomy was performed in 31 patients and bilateral craniectomy in 26 patients. In all cases, a wide frontotemporoparietal craniectomy was followed by a dura enlargement covered with temporal muscle fascia. The outcomes of the treatment were surprisingly good. Only 11 patients (19%) died, three of whom died of acute respiratory disease syndrome. Five patients (9%) survived, but remained in a persistent vegetative state; six patients (11%) survived with a severe permanent neurological deficit, and 33 patients (58%) attained social rehabilitation. Two patients (3.5%) did not have a follow-up examination. The GCS score on the 1st day posttrauma and the mean ICP turned out to be the best predictors for a good prognosis. The results demonstrate the importance of decompressive craniectomy in the treatment of traumatic brain swelling. CONCLUSIONS: Surgical decompression should be routinely performed when indicated before irreversible ischemic brain damage occurs.

Ionic modulation of triethyllead neurotoxicity in cerebellar granule cell culture.

While the molecular mechanism underlying triethyllead (TEL) neurotoxicity is unknown, we hypothesize that triethyllead mediates an accelerated Cl-/OH exchange across neuronal membranes leading to prolonged depolarization and neuronal cell injury. As a test of this hypothesis we have investigated the effect of external ion modulation on triethyllead neurotoxicity in cerebellar granule cell culture. Cultures were prepared from neonatal rats and used 10-20 days in vitro. Cytotoxicity was assessed by lactate dehydrogenase (LDH) release and trypan blue exclusion. A slow, dose-dependent (1-30 microM TEL) release of LDH occurred after a variable latent period dependent upon [TEL]. External replacement of [Cl-]e by Na isothionate dramatically shifted the dose response curve to the left reflecting an accelerated stimulation of LDH release, while replacement of extracellular [Na+]e with equimolar choline chloride had a minimal protective effect. Similarly, high [Mg2+]e or low [Ca2+]e did not protect or potentiate TEL cytotoxicity. The low [Cl-]e accelerated TEL cytotoxicity was dependent on medium pH: alkaline pH potentiated the cytotoxicity. Low [Cl-]e had no significant effect on culture ATP over 5 hrs. ATP reduction was markedly stimulated by TEL in low Cl- medium in contrast to the minimal decline in [ATP] in the control medium. The reduction of ATP in the low [Cl-]e medium occurred prior to LDH or trypan blue staining release confirming that such reduction in [ATP] was not secondary to cell damage. Substituting K sulfate or Na sulfate for the Cl(-)-free medium revealed marked loss of ATP without LDH release in control and TEL supplemented cultures. These observations provide supporting evidence for the role of an abnormal Cl- flux in mediating TEL-induced neurotoxic injury. Specifically, the membrane depolarization is proportional to the gradient imposed by Cl- efflux/OH influx, stimulated by low [Cl-]e. The rapid loss in ATP appeared early, was not a secondary reflection of neuronal damage but a result of a combination of increased ion flux at the plasma membrane, stimulation of Na+/K+ ATPase and direct TEL-induced inhibition of mitochondrial oxidative phosphorylation.

Long-term health-related quality of life after decompressive hemicraniectomy in stroke patients with life-threatening space-occupying brain edema.

BACKGROUND: Although randomized clinical trials have reported significant improvement in mortality and functional outcome as measured with modified Rankin Scale (mRS) or Barthel index (BI) in stroke patients with space-occupying anterior circulation infarctions treated with hemicraniectomy, many clinicians are still concerned about the long-term health-related quality of life (HRQoL). AIM: Assessment of HRQoL after hemicraniectomy to holistically reevaluate clinical outcome. METHODS: Eleven patients (6 men, 5 women; mean age 48 (SD 5.8) years) were examined at 9-51 months after hemicraniectomy. Test batteries comprised NIH stroke scale, BI, mRS, neuropsychological tests (Visual Object and Space Perception Battery and clock test), and HRQoL-scales (Short Form 36 Health Survey (SF-36), Nottingham Health Profile (NHP), Questions on Life Satisfaction, Hospital Anxiety and Depression Scale and EQ-5D). RESULTS: Median values for NIHSS, BI and mRS were 11.5, 55 and 3.5. In HRQoL-scales, subscales related to physical mobility and functioning were consistently severely impaired, while subscales related to psychological well-being were impaired to a lesser extent. Mean scores for physical functioning and physical role were 10.5 and 12.5 in the SF-36, and 61.3 and 43.3 for physical mobility and energy in the NHP; emotional role and mental health scored 63.3 and 66.4 (SF-36), scores for emotional reaction and social isolation were 18.9 and 16.0 (NHP), respectively. CONCLUSION: Although, physical components of HRQoL are highly impaired, these stroke patients achieved a satisfying level of psychological well-being which was endorsed by a nearly unanimous retrospective appraisal of life-saving hemicraniectomy.

Margen quirúrgico positivo de enfermedad neoplásica en conos cervical, según las técnicas de conización bajo visión directa o video colposcopía realizados en el INCAN / Positive surgical margins of neoplastic disease in cervical cones, according to techniques of conization under direct vision or video colposcopy performed in INCAN

En la Zona de Transformación del Cérvix, se produce las alteraciones epiteliales de las Neoplasias Cervicales por infección del Virus del Papiloma Humano (VPH), la conización cervical puede ser: terapéutico y diagnóstico...

There are two indications for cerviical conization: therapeutic and diagnostic neoplastic diseases It´s a challenge to get the piece of cervical cone without disease or positive margins at the edges especially when it is therapeutic...

Long-term results after microsurgical repair of traumatic nerve lesions of the upper extremities.

OBJECTIVE: Peripheral nerve injuries are still underestimated. This study examines the outcomes after surgical treatment of traumatic nerve lesions of the upper extremities. The different surgical techniques are analyzed with regard to the long-term outcome. METHODS: This retrospective study presents the data of 93 patients (female: 24; male: 69) who were operated on for peripheral nerve injuries of the upper extremities in our department between 1991 and 2003. Mean age was 31 years (range, 5-67 years). Altogether 100 traumatic nerve lesions (ulnar nerve: 20; radial nerve: 22; median nerve: 25; axillary nerve: 6; accessory nerve: 7; musculocutaneous nerve: 2; long thoracic nerve: 1; digital nerve: 3; combined nerves: 7) were surgically treated. Surgical management included primary nerve suture in 16, neurolysis in 25, and nerve grafting in 59 patients. RESULTS: 74 patients (80%) were available for follow-up examination. The mean follow-up period was 35 months (range, 18-132 months). All patients up to the age of 20 years demonstrated good or excellent sensorimotor recovery. A good functional outcome was observed in 79% of the patients older than 20 years. Overall, good to excellent improvements of motor function were achieved for lesions of the musculocutaneous, radial, accessory and axillary nerves (100%, 89%, 100%, 100% functional useful muscle innervation, muscle recovery grade 3 and more). The length of grafts, in cases of secondary nerve reconstruction, did not influence functional outcome. CONCLUSION: Generally, early surgical repair of a nerve lesion predicted a better outcome. A good functional motor recovery was dependent on the age of the patient. Traumatic nerve lesions, without signs of reinnervation, should be treated surgically within a period of three months after injury.

Patient satisfaction and diagnostic accuracy with ultrasound by emergency physicians.

In recent years, there has been considerable interest and controversy concerning the performance of ultrasound by emergency physicians (ED Sono), but patient satisfaction with ED Sono has not been well studied. The primary purpose of this investigation was to assess the level of patient satisfaction with ED Sono and to compare satisfaction with ED Sono with ultrasound by the Medical Imaging Department (MI Sono). A secondary objective was to assess the accuracy of ED Sono at our facility. During a 5-month period, which included the startup phase of a program for ED Sono, emergency physicians prospectively identified patients who were candidates for ultrasound as a part of their workup. Patients were contacted by telephone after their ED visit and asked to rate satisfaction on a 0 to 10 scale for various aspects of their care, including the ultrasound if one was done. The accuracy of ED Sono was determined by comparing ED ultrasound interpretations with surgical pathology, repeat imaging studies, or clinical follow-up. Two hundred forty patients were entered into the study, and 186 (78%) responded to the satisfaction survey. Satisfaction ratings were similarly high for ED Sono (mean, 8.9; 95% Cl, 8.6 to 9.2) and for MI Sono (mean, 8.8; 95% Cl, 8.2 to 9.4). Eighteen percent of ultrasounds performed by emergency physicians were indeterminate. Excluding indeterminate scans and scans for which confirmation was not possible, the accuracy of ED Sono was 99.1% (95% Cl, 95.1% to >99.9%). We conclude that during the startup phase of our ED Sono program, patient satisfaction was high, and the error rate was very low.

The neuropathology of AIDS. UCLA experience and review.

The central nervous system (CNS) has been examined at autopsy in 89 patients who died of the acquired immune deficiency syndrome (AIDS), including 14 patients who died primarily of neurologic complications of the disease. A total of 66 brains (74%) showed significant pathologic abnormalities, with opportunistic infections including cytomegalovirus (14) and cryptococcal (11) infections, progressive multifocal leukoencephalopathy (6), toxoplasmosis (6), and histoplasma microabscesses (1). Incidental Mycobacterium avium-intracellulare infection was found in 4 cases. Simultaneous CNS infection by more than one microorganism was encountered in 5 patients. Subacute (microglial nodule) encephalitis-related to cytomegalovirus infection or possibly brain infection by the causative agent of AIDS was present in 56 cases. Primary CNS lymphoma was noted in 3 patients. Secondary CNS deposits of lymphoma were found in 1 patient, and another patient had lymphomatoid granulomatosis. Vascular complications were not infrequently seen, and included infarcts secondary to vessel occlusion and disseminated intravascular coagulation in 4 patients and intracranial hemorrhage of variable severity in 13. White matter changes included vacuolar myelopathy (3 cases), central pontine myelinolysis (1 case), and foci of calcified, necrotizing leukoencephalopathy in pontocerebellar fibers of the basis pontis (2 cases). These findings highlight the variety of CNS complications in AIDS, some of which are not associated with clinical manifestations. Nevertheless, characterization of all lesions may be important in understanding the neurologic sequelae of AIDS.

Ultrasound availability in the evaluation of ectopic pregnancy in the ED: comparison of quality and cost-effectiveness with different approaches.

The liberal use of ultrasonography has been advocated in patients with first trimester cramping or bleeding to avoid misdiagnosis of ectopic pregnancy in the emergency department (ED). The cost-effectiveness of different approaches to ultrasound availability has not been previously reported. In this study, we investigated measures of quality and cost-effectiveness in detecting ectopic pregnancy in the ED over a 6-year period, divided into three approximately equal epochs with three distinct approaches to ultrasound availability. The study retrospectively identified 120 cases of ectopic pregnancy seen in the ED over 6 years. There was significant improvement in the percentage of patients with ectopic pregnancy who were documented to have absence of intrauterine pregnancy (IUP) at the first visit from 76% during Epoch 1, when there was limited availability of ultrasound through medical imaging (MI Sono), to 88% in Epoch 2, when MI Sono was readily available, to 96% in Epoch 3, when both MI Sono and ultrasound by emergency physicians (ED Sono) were readily available (P = .02). The estimated number of MI Sonos ordered by emergency physicians in patients at risk for ectopic pregnancy increased from 5.2 per ectopic pregnancy in Epoch 1 to 11.8 per ectopic pregnancy in Epoch 2, and declined to 5.5 per ectopic pregnancy in Epoch 3, when 19.9 ED Sonos per ectopic pregnancy were also done. The cost of ED Sono in Epoch 3 was more than offset by savings from avoiding calling in ultrasound technicians after regular medical imaging department hours. The specificity of ED Sono in ruling in an IUP was 100% (95% CI 98.3 to 100%), but analysis of secondary quality indicators reflecting times from first ED visit to treatment in Epoch 3 raised the possibility that an adnexal mass or signs of tubal rupture may have been missed on some ED Sonos. We conclude that increased availability of ultrasonography leads to improved quality in the detection of ectopic pregnancy in the ED, but at the expense of a disproportionate increase in the number of ultrasound studies done per ectopic pregnancy detected. Our study suggests that the most cost-effective strategy is for emergency physicians to screen all patients with first trimester cramping and bleeding with ED Sonos, and to obtain MI Sonos at the time of the initial ED visit in all cases in which the ED Sono is indeterminate or shows no IUP.

Necrotizing vasculitis of the nervous system in a patient with AIDS-related complex.

A patient with AIDS-related complex (ARC) presented with a fulminant neurologic syndrome suggestive of ascending myelopathy, and died approximately 48 h after admission to hospital. At necropsy, there was evidence of a severe necrotizing vasculitis affecting the nervous system most severely, with multifocal haemorrhagic necroses of the spinal cord and cauda equina. Although a rare intranuclear inclusion suggestive of herpesvirus infection was seen in the predominantly lympho-histiocytic infiltrate in and around blood vessel walls, the precise aetiology of the angiitis was not apparent. It may represent a response to AIDS virus infection of one or more components of the blood vessel wall.

Comparison of quality and cost-effectiveness in the evaluation of symptomatic cholelithiasis with different approaches to ultrasound availability in the ED.

Ultrasound is the imaging study of choice for the detection of gallstones, but ultrasound through medical imaging departments (MI Sono) is not readily available on an immediate basis in many emergency departments (EDs). Several studies have shown that emergency physicians can perform ultrasound themselves (ED Sono) to rule out gallstones with acceptable accuracy after relatively brief training periods, but there have been no studies to date specifically addressing the effect of ED Sono of the gallbladder on quality and cost-effectiveness in the ED. In this study, we investigated measures of quality and cost-effectiveness in evaluating patients with suspected symptomatic cholelithiasis during three different years with distinctly different approaches to ultrasound availability. The study retrospectively identified a total of 418 patients who were admitted for cholecystectomy or for a complication of cholelithiasis within 6 months of an ED visit for possible biliary colic. The percentage of patients who had gallstones documented at the first ED visit improved from 28% in 1993, when there was limited availability of ultrasound through the Medical Imaging Department (MI Sono), to 56% in 1995, when MI Sono was readily available, to 70% in 1997, when both MI Sono and ED Sono were readily available (P <.001). There were also significant differences over the 3 years in the mean number of days from the first ED visit to documentation of gallstones (19.7 in 1993, 10.7 in 1995, 7.4 in 1997, P <.001); the mean number of return visits for possible biliary colic before documentation of gallstones (1.67 in 1993, 1.24 in 1995, and 1.25 in 1997, P <.001); and the incidence of complications of cholelithiasis in the interval between the first ED visit for possible biliary colic and the date of documentation of cholelithiasis (6.8% in 1993, 5.9% in 1995, 1.5% in 1997, P =.049). The number of MI Sonos ordered by emergency physicians per case of symptomatic cholelithiasis identified increased from 1.7 in 1993 to 2.5 in 1995 and dropped back to 1.7 in 1997, when 4.2 ED Sonos per study case were also done. The cost of ED Sonos was more than offset by savings in avoiding calling in ultrasound technicians after regular Medical Imaging Department hours. The indeterminate rate for ED Sonos was 18%. Excluding indeterminates, the sensitivity of ED Sono for detection of gallstones was 88.6% (95% CI 83.1-92.8%), the specificity 98.2% (95% CI 96.0-99.3%), and the accuracy 94.8% (95% CI 92.5-96.5%). We conclude that greater availability of MI Sono in the ED was associated with improved quality in the evaluation of patients with suspected symptomatic cholelithiasis but also with increased ultrasound costs. The availability of ED Sono in addition to readily available MI Sono was associated with further improved quality and decreased costs. The indeterminate rate for ED Sono was relatively high, but excluding indeterminates, the accuracy of ED Sono was comparable with published reports of MI Sono.