Isquemia aguda por trombosis aórtica en COVID-19: A propósito de un caso

Objetivo: Presentar un caso de isquemia aguda por trombosis aórtica en paciente con infección por COVID-19 y exponer la importancia del diagnóstico y manejo oportuno. Introducción: El coronavirus (COVID-19) afecta principalmente al tracto respiratorio, pero presenta predisposición a fenómenos trombóticos y sus complicaciones, siendo una de las más graves la isquemia aguda por trombosis aórtica. Caso clínico: Paciente masculino de 68 años, que cursa con cuadro clínico de neumonía grave por COVID-19, presenta de forma concomitante episodio de trombosis aórtica aguda, resultando con isquemia aguda de extremidades inferiores. Se realizó trombectomía, post procedimiento y asociado a reperfusión, presentó paro cardiorrespiratorio con asistolia sostenida, falleciendo pese a maniobras de reanimación. Conclusión: Pese a las medidas de profilaxis con heparina de bajo peso molecular (HBPM), se deben sospechar y buscar las complicaciones tromboembólicas en pacientes que cursan con esta infección para dar un manejo oportuno y vigilar las complicaciones post quirúrgicas que pueden ser mortales.

Aim: To present a case of acute ischemia due to aortic thrombosis in a patient with COVID-19 infection and explain the importance of diagnosis and timely management. Introduction: The coronavirus (COVID-19) mainly affects the respiratory tract, but it has a predisposition to thrombotic phenomena and its complications, one of the most serious being acute ischemia due to aortic thrombosis. Clinical case: 68-year-old man, coronary heart disease with severe pneumonia due to COVID-19, presents aortic thrombosis, resulting in acute lower extremity ischemia. Thrombectomy was performed, post procedure and associated with reperfusion, presented cardiorespiratory arrest with sustained asystole, died despite resuscitation maneuvers. Conclusion: Despite prophylaxis measures with low molecular-weight heparins (LMWH), thromboembolic complications should be sought in patients with this infection to provide timely management and monitor post-surgical complications that can be fatal.

A scoping review of the analytical literature concerning nonambulatory dairy cattle.

Nonambulatory dairy cattle pose a complex problem due to the challenges associated with prevention, appropriate treatment and management, and arriving at an accurate prognosis. There is a breadth of literature regarding this topic, of which there is currently no formal synthesis. The objective of this scoping review was to describe and characterize the literature investigating risk factors, sequela, preventions, treatments, and prognostic factors for nonambulatory conditions in dairy cattle, with the intent of qualitatively synthesizing knowledge of the topic and identifying gaps in the literature. A literature search was conducted in 6 databases and 2 conference proceeding archives, which returned 7,568 unique articles. Initial screening of abstracts resulted in 1,544 articles reviewed at the full-text stage, of which 379 were included for data extraction. Over 75% of the included literature was published after 1980, and the most common countries in which these studies took place were the United States (n = 72), Canada (18), Sweden (17), and Germany (17). Common eligibility criteria used for inclusion were geographic region (97) and parity (92). Of the 379 studies included in this review, 144 were randomized controlled trials and 235 were observational studies. The majority of the controlled trials assessed prevention of nonambulatory conditions (116), most commonly through supplementation of vitamin D (27) and calcium (25) or the provision of anionic salts (22). Of the 28 studies focusing on treatment of nonambulatory conditions, 26 focused on calcium administration. Becoming nonambulatory was evaluated as an outcome in 165 of the observational studies. Frequently measured risk factors for becoming nonambulatory included hematological variables, such as blood calcium (73), phosphorus (53) and magnesium (42), and other factors such as parity (35) and breed (22). Recovery from a nonambulatory condition was the outcome in 31 of the observational studies, with commonly measured prognostic indicators being calcium (9), phosphorus (9), and duration of recumbency (7). Nonambulatory disorders were measured as risk factors in 53 of the observational studies, with the most commonly assessed outcomes including disorders of the transition period (11), and death or euthanasia (11). The most common terms used to describe nonambulatory conditions were "milk fever" (199) and "parturient paresis" (147). These terms were only further defined with explicit symptomatic criteria in 193 of the 379 studies in this review. Recumbency was the most commonly used of these criteria (144), followed by inability to rise (55). Potential gaps in the literature concerning nonambulatory dairy cattle that were identified in the present review included investigation of prognostic indicators for recovery from nonambulatory conditions that are applicable on farm, treatment alternatives to calcium administration, and guidance regarding the appropriate usage of terms meant to categorize nonambulatory dairy cattle.

Lateral condylar fractures of the humerus in children: does the type of fixation matter?

Aims: Displaced fractures of the lateral condyle of the humerus are frequently managed surgically with the aim of avoiding nonunion, malunion, disturbances of growth and later arthritis. The ideal method of fixation is however not known, and treatment varies between surgeons and hospitals. The aim of this study was to compare the outcome of two well-established forms of surgical treatment, Kirschner wire (K-wire) and screw fixation. Patients and Methods: A retrospective cohort study of children who underwent surgical treatment for a fracture of the lateral condyle of the humerus between January 2005 and December 2014 at two centres was undertaken. Pre, intraoperative and postoperative characteristics were evaluated. A total of 336 children were included in the study. Their mean age at the time of injury was 5.8 years (0 to 15) with a male:female patient ratio of 3:2. A total of 243 (72%) had a Milch II fracture and the fracture was displaced by > 2 mm in 228 (68%). In all, 235 patients underwent K-wire fixation and 101 had screw fixation. Results: There was a higher rate of nonunion with K-wire fixation (p = 0.02). There was no difference in Baumann's angle, carrying angle or the rate of major complications between the two groups. No benefit was obtained by immobilizing the elbow for more than four weeks in either group. No short-term complications were seen when fixation crossed the lateral ossific nucleus. Conclusion: Fixation of lateral condylar humeral fractures in children using either K-wires or screws gives satisfactory results. Proponents of both techniques may find justification of their methods in our data, but prospective, randomized trials with long-term follow-up are required to confirm the findings, which suggest a higher rate of nonunion with K-wire fixation. Cite this article: Bone Joint J 2018;100-B:387-95.

The balancing act of foraging: mammalian herbivores trade-off multiple risks when selecting food patches.

Animals face multiple risks while foraging such as the risk of acquiring inadequate energy from food and the risk of predation. We evaluated how two sympatric rabbits (pygmy rabbits, Brachylagus idahoensis, and mountain cottontail rabbits, Sylvilagus nuttallii) that differ in size, use of burrows, and habitat specialization in the sagebrush-steppe of western North America respond to different types and levels of perceived risks (i.e., fitness cost × probability of occurrence), including fiber and toxins in food, exposure to predation, and distance from a refuge. We measured food intake by the rabbits at paired food patches that varied in these risks and used the method of paired comparisons to create a relative ranking of habitat cues, which revealed an animal's perceived risk on a single scale representing an integrated response to a variety of risks. Pygmy rabbits perceived exposure to predation risk and distance from a burrow as riskier than did cottontails, whereas cottontails perceived dietary toxin as riskier. Pygmy rabbits consumed lower quality food, containing higher fiber or toxins, thereby avoided feeding in exposed patches or traveling far from their burrow to forage. In contrast, cottontails fed in exposed patches and traveled farther from the burrow to obtain higher quality food. We have shown how risks can be integrated into a single model that allows animals to reveal their perceptions of risks on a single scale that can be used to create a spatially explicit landscape of risk.

Proximal femoral osteotomy in children with cerebral palsy: the perspective of the trainee.

BACKGROUND: There are a range of implants for fixation of proximal femoral osteotomies (PFOs) in children. We investigated the training experiences and preferences of orthopaedic residents and fellows who were learning PFO, using a fixed angled blade plate (ABP) or a locking, cannulated blade plate (LCBP). We also studied short-term technical and radiographic outcomes. METHODS: This was a prospective, parallel-group, cohort study of 90 consecutive children and adolescents with cerebral palsy who underwent bilateral PFOs with ABP or LCBP. Surgical trainees completed a questionnaire to document the ease or difficulty of each operative step. RESULTS: There were 48 boys and 42 girls, with a mean age of eight years and a mean follow-up of 25 months. Trainees preferred the LCBP system for: insertion of the guidewire, the seating chisel and the blade plate, as well as overall technical ease of use (p < 0.001). Radiographic outcomes were similar with no between-group differences for migration percentage (p = 0.996) or neck shaft angle (p = 0.849), but there was a higher prevalence of technical errors in the ABP group. CONCLUSIONS: Trainee surgeons expressed a preference for LCBPs when learning PFO in children with cerebral palsy. Radiographic outcomes were similar in both groups, with close attending surgeon supervision.

Timing and duration of nursing from birth affect neonatal porcine uterine matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1.

Nursing for 2 d from birth supports neonatal porcine uterine and cervical development. However, it is not clear how timing or duration of lactocrine signaling from birth (postnatal day = PND 0) affects development of neonatal female reproductive tract tissues. Therefore, studies were conducted to determine effects of age at first nursing and duration of nursing from birth on specific elements of the matrix metalloproteinase (MMP)/tissue inhibitor of metalloproteinase (TIMP) system in uterine and cervical tissues at PND 2. When nursing was initiated at 0 h or 30 min of age, targeted proteins, including proMMP9 and MMP9, were detected in uterine and cervical tissues on PND 2, as was uterine TIMP1. However, these proteins were undetectable when nursing was delayed for 12 h and when gilts were fed milk replacer for 48 h from birth. Increasing the duration of nursing from 30 min to 12 h from birth increased uterine (P < 0.05) and cervical (P < 0.001) MMP9 levels to those observed in gilts nursed for 48 h. Similarly, uterine TIMP1 levels increased with duration of nursing. Uterine MMP2 levels were detectable but unaffected by age at first nursing or duration of nursing from birth. Uterine MMP2 and MMP9 activities, monitored by zymography, reflected immunoblotting data. Results provide evidence for the utility of MMP9 and TIMP1 as markers of age- and lactocrine-sensitive porcine female reproductive tract development.

Reducing resource utilization during non-operative treatment of pediatric proximal humerus fractures.

INTRODUCTION: The majority of proximal humeral fractures in the skeletally immature are treated non-operatively. Operative indications vary but are largely based on degree of displacement. Non-union is rare. Non-operatively treated fractures are typically monitored radiographically to assess healing. HYPOTHESIS: We hypothesize that the decision to treat fractures operatively is made at the time of first imaging and that follow-up X-rays do not lead to a change in management. MATERIAL AND METHODS: We retrospectively reviewed the records of 239 patients treated for proximal humerus fractures over a 5-year period. There were 225 who were treated non-operatively. Records were reviewed for the number of clinic visits and radiographs, as well as any change to operative management based on follow-up X-rays. RESULTS: The primary outcome of the study was the proportion of proximal humerus fractures, initially treated non-operatively, for which displacement or angulation on follow-up radiographs led to a change to operative treatment. Secondary outcomes were the number of follow-up radiographs obtained after the initial diagnosis and initiation of non-operative treatment. Of the 225 patients that were initially managed non-operatively, only 1 patient required subsequent surgical management. This patient underwent a proximal humerus epiphysiodesis 365 days from injury after development of a partial growth arrest. The mean number of fracture clinic visits for patients managed non-operatively was 2.67 (±1.24). The mean number of radiology department visits and radiographs obtained was 3.57 (±1.44) and 8.36 (±3.89) respectively. No clinical or radiographic non-unions were identified in these patients. No patients suffered a refracture during the review period. DISCUSSION: This study shows that of the 239 uncomplicated pediatric proximal humerus fractures treated at our hospital over a 5-year period, only 1 had a change in treatment plan, from non-operative to operative, based on follow-up radiographs. These data suggest that non-operative treatment of proximal humerus fractures seldom results in displacement that warrants operative intervention. Moreover, they suggest that there is little utility to the routine use of postoperative radiographs in follow-up of these patients. STUDY DESIGN: Retrospective case series. LEVEL OF EVIDENCE: IV.

Observations of turkey eggs stored up to 27 days and incubated for 8 days: embryo developmental stage and weight differences and the differentiation of fertilized from unfertilized germinal discs.

For logistical reasons, egg storage prior to incubation is a growing practice in the commercial turkey industry. Yet the consequence of increasing egg storage over 7 d is a progressive increase in embryo mortality. The objective of this study was to provide the information necessary to differentiate an early dead embryo from an unfertilized egg after 8 days of incubation (DOI). Five groups of eggs each from inseminated and virgin hens were stored for progressively increasing periods of time (5-d or less, 6 to 10 d, 11 to 15 d, 16 to 20 d, and 21 to 27 d) and incubated. At 8 DOI, eggs were examined and the stage of development (Hamburger and Hamilton, 1951) and embryo weights in normally developed eggs were determined. There was a significant negative correlation between the stage of development and embryo weight with increasing storage periods. All remaining eggs from the inseminated and virgin hens were broken-out and the appearance of the yolk and the fertilized and unfertilized germinal discs examined. The yolks of both hen groups with unfertilized ova maintained a homogeneous uniform yellow-orange color. In contrast, yolks of ova that had been fertilized, with or without early-dead embryos, and yolks from virgin hens that showed evidence of parthenogenetic development (3%) had a heterogeneous appearance. Using fluorescence microscopy, the heterogeneous appearance was due to sheets of aberrant cells and less frequently dispersed cells and folds of the perivitelline layer. It was concluded that clear egg breakouts need to be performed to more accurately assess the impact of egg storage on embryonic mortality. Furthermore, such breakouts should be performed with a high intensity light directed across the surface of the germinal disc to clearly differentiate the subtle differences between an early-dead embryo and an unfertilized germinal disc.

Durable fear memories require PSD-95.

Traumatic fear memories are highly durable but also dynamic, undergoing repeated reactivation and rehearsal over time. Although overly persistent fear memories underlie anxiety disorders, such as posttraumatic stress disorder, the key neural and molecular mechanisms underlying fear memory durability remain unclear. Postsynaptic density 95 (PSD-95) is a synaptic protein regulating glutamate receptor anchoring, synaptic stability and certain types of memory. Using a loss-of-function mutant mouse lacking the guanylate kinase domain of PSD-95 (PSD-95(GK)), we analyzed the contribution of PSD-95 to fear memory formation and retrieval, and sought to identify the neural basis of PSD-95-mediated memory maintenance using ex vivo immediate-early gene mapping, in vivo neuronal recordings and viral-mediated knockdown (KD) approaches. We show that PSD-95 is dispensable for the formation and expression of recent fear memories, but essential for the formation of precise and flexible fear memories and for the maintenance of memories at remote time points. The failure of PSD-95(GK) mice to retrieve remote cued fear memory was associated with hypoactivation of the infralimbic (IL) cortex (but not the anterior cingulate cortex (ACC) or prelimbic cortex), reduced IL single-unit firing and bursting, and attenuated IL gamma and theta oscillations. Adeno-associated virus-mediated PSD-95 KD in the IL, but not the ACC, was sufficient to impair recent fear extinction and remote fear memory, and remodel IL dendritic spines. Collectively, these data identify PSD-95 in the IL as a critical mechanism supporting the durability of fear memories over time. These preclinical findings have implications for developing novel approaches to treating trauma-based anxiety disorders that target the weakening of overly persistent fear memories.

Nursing supports neonatal porcine testicular development.

The lactocrine hypothesis suggests a mechanism whereby milk-borne bioactive factors delivered to nursing offspring affect development of neonatal tissues. The objective of this study was to assess whether nursing affects testicular development in neonatal boars as reflected by: (1) Sertoli cell number and proliferation measured by GATA-4 expression and proliferating cell nuclear antigen immunostaining patterns; (2) Leydig cell development and steroidogenic activity as reflected by insulin-like factor 3 (INSL3), and P450 side chain cleavage (scc) enzyme expression; and (3) expression of estrogen receptor-alpha (ESR1), vascular endothelial growth factor (VEGF) A, and relaxin family peptide receptor (RXFP) 1. At birth, boars were randomly assigned (n = 6-7/group) to nurse ad libitum or to be pan fed porcine milk replacer for 48 h. Testes were collected from boars at birth, before nursing and from nursed and replacer-fed boars at 50 h on postnatal day (PND) 2. Sertoli cell proliferating cell nuclear antigen labeling index increased (P < 0.01) from birth to PND 2 in nursed, but not in replacer-fed boars. Sertoli cell number and testicular GATA-4 protein levels increased (P < 0.01) from PND 0 to PND 2 only in nursed boars. Neither age nor nursing affected testicular INSL3, P450scc, ESR1, or VEGFA levels. However, testicular relaxin family peptide receptor 1 (RXFP1) levels increased (P < 0.01) with age and were greater in replacer-fed boars on PND 2. Results suggest that nursing supports neonatal porcine testicular development and provide additional evidence for the importance of lactocrine signaling in pigs.

Lactation Biology Symposium: lactocrine signaling and developmental programming.

Lactocrine signaling is defined as transmission of bioactive factors from mother to offspring as a consequence of nursing. Lactocrine transmission of signaling molecules may be an evolutionarily conserved process through which bioactive factors necessary for support of neonatal development are delivered postnatally. Dependence on maternal resources for development in eutherian mammals extends into neonatal life for at least that period of time when nutrition is obtained solely from first milk (i.e., colostrum). Data for the pig (Sus scrofa domesticus) provide evidence of lactocrine mediated effects on development of the female reproductive tract and other somatic tissues. Porcine uterine gland development, an estrogen receptor-alpha (ESR1)-dependent process, begins within 2 d of birth [postnatal day (PND) 0]. A lactocrine-driven, ESR1-mediated process was proposed as a regulatory mechanism governing onset of uterine gland development and endometrial maturation in the neonatal pig. Gilts maintained in a lactocrine-null state for 2 d from birth by milk-replacer feeding displayed altered patterns of endometrial gene expression and retarded uterine gland development by PND 14. In lactocrine-null gilts, inhibition of endometrial and cervical ESR1 and vascular endothelial growth factor (VEGFA) expression observed on PND 2 persisted to PND 14, even after gilts were returned to nursing on PND 2. Collectively, data support a role for lactocrine signaling in regulation of critical neonatal developmental events. Maternal lactocrine programming of postnatal development may help to insure healthy developmental outcomes. A systems biology approach will be required to define and understand mechanistic dynamics of lactocrine signaling events that may ultimately connect genotype to phenotype and establish the parameters of reproductive potential.

[Pre-washing catheter dramatically improves the post intrauterine insemination pregnancy rate]. / Le rinçage des cathéters avant insémination intra-utérine augmente considérablement les taux de grossesses.

OBJECTIVE: To analyze the effectiveness of pre-washing the intrauterine insemination catheters on IUI outcome. PATIENTS AND METHODS: Infertile couples (n=322) involved in a IUI program were included in the study. IUI indications were cervical factors, ovulation dysfunction, cryopreserved semen and unexplained infertility. Every other week for two years, IUI catheters were washed with culture medium prior to intrauterine sperm insemination. RESULT(S): Only the first IUI for each couple were analyzed. Washing the catheter, prior to use, resulted in a 49.7% increase in clinical pregnancy rate (22.0% vs 14.7% P<0.05). This result is observed with fresh sperm (15.7% vs 11.1%) and frozen-thawed sperm as well (31.1% vs 19.8%). The early pregnancy termination rate was similar in all groups. DISCUSSION AND CONCLUSION: Pre-washing the catheter before IUI should be recommended in Good Laboratory Practice Guidelines as it is already the case for embryo transfer catheters. This raises the problem of washing all single-use devices, in contact with gametes or embryos during IVF.

Use of zero-valent iron biosand filters to reduce Escherichia coli O157:H12 in irrigation water applied to spinach plants in a field setting.

AIMS: Zero-valent iron (ZVI) filters may provide an efficient method to mitigate the contamination of produce crops through irrigation water. METHODS: A field-scale system was utilized to evaluate the effectiveness of a biosand filter (S), a biosand filter with ZVI incorporated (ZVI) and a control (C, no treatment) in decontaminating irrigation water. An inoculum of c.8·5log CFU100ml(-1) of Escherichia coli O157:H12 was introduced to all three column treatments in 20-l doses. Filtered waters were subsequently overhead irrigated to 'Tyee' spinach plants. Water, spinach plant and soil samples were obtained on days 0, 1, 4, 6, 8, 10, 13 and 15 and analysed for E. coli O157:H12 populations. RESULTS: ZVI filters inactivated c.6logCFU100ml(-1) E. coli O157:H12 during filtration on day 0, significantly (P<0·05) more than S filter (0·49CFU100ml(-1)) when compared to control on day 0 (8·3log CFU100ml(-1)). On day 0, spinach plants irrigated with ZVI-filtered water had significantly lower E. coli O157 counts (0·13logCFUg(-1)) than spinach irrigated with either S-filtered (4·37logCFUg(-1)) or control (5·23logCFUg(-1)) water. Soils irrigated with ZVI-filtered water contained E. coli O157:H12 populations below the detection limit (2logCFUg(-1)), while those irrigated with S-filtered water (3·56logCFUg(-1)) were significantly lower than those irrigated with control (4·64logCFUg(-1)). CONCLUSIONS: ZVI biosand filters were more effective in reducing E. coli O157:H12 populations in irrigation water than sand filters. SIGNIFICANCE AND IMPACT OF THE STUDY: Zero-valent ion treatment may be a cost-effective mitigation step to help small farmers reduce risk of foodborne E. coli infections associated with contamination of leafy greens.

Comparisons of sperm storage tubule distribution and number in 4 strains of mature broiler breeders and in turkey hens before and after the onset of photostimulation.

The biological basis of sustained fertility in broiler and turkey hens is their capacity to store sperm in the oviductal sperm storage tubules (SST) located in the uterovaginal junction. The objectives of this study were to determine if the numbers of SST varied between 4 strains of broiler breeders and determine the number of SST in the turkey before (less than 9 d of photostimulation) and after (up to 22 d of photostimulation and laying) photostimulation. No statistical differences were observed in SST numbers in the 4 strains of broilers examined or in turkey hens before and after the onset of egg production. The mean numbers of SST for broilers and turkeys were 4,893 and 30,566, respectively. We conclude that any differences between the fertility of the 4 broiler breeder strains examined cannot be explained by differences in SST numbers. However, differences in the duration of fertility between broilers and turkeys are, in part, related to their respective numbers of number of SST. Furthermore, we conclude that turkey SST are morphologically differentiated and functional before the onset of photostimulation and while the oviduct is morphologically undeveloped.

Impaired Pavlovian fear extinction is a common phenotype across genetic lineages of the 129 inbred mouse strain.

Fear extinction is impaired in psychiatric disorders such as post-traumatic stress disorder and schizophrenia, which have a major genetic component. However, the genetic factors underlying individual variability in fear extinction remain to be determined. By comparing a panel of inbred mouse strains, we recently identified a strain, 129S1/SvImJ (129S1), that exhibits a profound and selective deficit in Pavlovian fear extinction, and associated abnormalities in functional activation of a key prefrontal-amygdala circuit, as compared with C57BL/6J. The first aim of the present study was to assess fear extinction across multiple 129 substrains representing the strain's four different genetic lineages (parental, steel, teratoma and contaminated). Results showed that 129P1/ReJ, 129P3/J, 129T2/SvEmsJ and 129X1/SvJ exhibited poor fear extinction, relative to C57BL/6J, while 129S1 showed evidence of fear incubation. On the basis of these results, the second aim was to further characterize the nature and specificity of the extinction phenotype in 129S1, as an exemplar of the 129 substrains. Results showed that the extinction deficit in 129S1 was neither the result of a failure to habituate to a sensitized fear response nor an artifact of a fear response to (unconditioned) tone per se. A stronger conditioning protocol (i.e. five x higher intensity shocks) produced an increase in fear expression in 129S1, relative to C57BL/6J, due to rapid rise in freezing during tone presentation. Taken together, these data show that impaired fear extinction is a phenotypic feature common across 129 substrains, and provide preliminary evidence that impaired fear extinction in 129S1 may reflect a pro-fear incubation-like process.

Examination of bacteriophage as a biocontrol method for salmonella on fresh-cut fruit: a model study.

The preparation and distribution of fresh-cut produce is a rapidly developing industry that provides the consumer with convenient and nutritious food. However, fresh-cut fruits and vegetables may represent an increased food safety concern because of the absence or damage of peel and rind, which normally help reduce colonization of uncut produce with pathogenic bacteria. In this study, we found that Salmonella Enteritidis populations can (i) survive on fresh-cut melons and apples stored at 5 degrees C, (ii) increase up to 2 log units on fresh-cut fruits stored at 10 degrees C, and (iii) increase up to 5 log units at 20 degrees C during a storage period of 168 h. In addition, we examined the effect of lytic, Salmonella-specific phages on reducing Salmonella numbers in experimentally contaminated fresh-cut melons and apples stored at various temperatures. We found that the phage mixture reduced Salmonella populations by approximately 3.5 logs on honeydew melon slices stored at 5 and 10 degrees C and by approximately 2.5 logs on slices stored at 20 degrees C, which is greater than the maximal amount achieved using chemical sanitizers. However, the phages did not significantly reduce Salmonella populations on the apple slices at any of the three temperatures. The titer of the phage preparation remained relatively stable on melon slices, whereas on apple slices the titer decreased to nondetectable levels in 48 h at all temperatures tested. Inactivation of phages, possibly by the acidic pH of apple slices (pH 4.2 versus pH 5.8 for melon slices), may have contributed to their inability to reduce Salmonella contamination in the apple slices. Higher phage concentrations and/or the use of low-pH-tolerant phage mutants may be required to increase the efficacy of the phage treatment in reducing Salmonella contamination of fresh-cut produce with a low pH.

Interaction of two novel 14-epivitamin D3 analogs with vitamin D3 receptor-retinoid X receptor heterodimers on vitamin D3 responsive elements.

This study provides a detailed and exact evaluation of the interactions between vitamin D3 receptor (VDR), retinoid X receptor (RXR), and vitamin D3 responsive elements (VDREs) mediated by two novel 14-epianalogs of 1,25-dihydroxyvitamin D [1,25(OH)2D3], 19-nor-14-epi-23-yne-1,25(OH)2D3 (TX 522) and 19-nor-14,20-bisepi-23-yne-1,25(OH)2D3 (TX 527). Both analogs were more potent (14- and 75-fold, respectively) than 1,25(OH)2D3 in inhibiting cell proliferation and inducing cell differentiation. However, DNA-independent experiments indicated that both analogs had a lower affinity to VDR and that the stability of the induced VDR conformation, as measured by limited protease digestion assays, was similar (TX 527) or even weaker (TX 522) than that induced by the parent compound. However, DNA-dependent assays such as gel shift experiments revealed that those analogs were slightly more potent (3-7 times) than 1,25(OH)2D3 in enhancing binding of VDR-RXR heterodimers to a direct repeat spaced by three nucleotides (DR3) type VDRE. The functional consequences of the ligand-VDR-RXR-VDRE interactions observed in vitro were subsequently evaluated in transfection experiments. Both 14-epianalogs enhanced transcription of VDRE containing reporter constructs more efficiently than 1,25(OH)2D3 in COS-1 and MCF-7 cells regardless of the presence of ketoconazole. Transactivation activity is suggested to be a cell-specific process because maximal transcriptional induction and the half-maximal transactivation concentration for each reporter construct were different in both cell lines. The superagonistic transactivation activity closely resembled the biological potency of these analogs on the inhibition of MCF-7 cell proliferation. These data clearly indicate that superagonistic activity starts beyond the binding of the ligand-heterodimer (VDR-RXR) complex to VDRE and thus probably involves coactivator/corepressor molecules.

Synthesis and characterization of fluorinated and iodinated pyrrolopyrimidines as PET/SPECT ligands for the CRF1 receptor.

Fluorine-18 labeled fluorobutyl[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo [2,3-d] pyrimidin-4-yl]ethylamine (FBPPA) and iodine-123 labeled butyl[2,5-dimethyl-7-(4-iodo-2,6-dimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]ethyl-amine (IBPPA) were synthesized in the development of a CRF receptor ligand. The methods of synthesis, in vitro binding assays, radiolabeling and in vivo tissue distribution in rats are described. Fluorine-18 labeled FBPPA was prepared with high specific activity (3 x 10(4) Ci/mmol) by nucleophilic displacement with an average radiochemical yield of 6% (EOB). Iodine-123 labeled IBPPA was prepared by electrophilic iododestannylation with good yield (60%) and high specific activity (3.3 x 10(3) Ci/mmol). The retention of FBPPA and IBPPA in the pituitary was good (1.16% i.d./g and 2.35% i.d./g respectively at 60 min). However, the accumulation of radioactivity in the brain for both radiotracers was very low at all time points of the study, which demonstrated the difficulties for these radiopharmaceuticals to penetrate the blood brain barrier (BBB).

The use of service dogs as an adaptive strategy: a qualitative study.

OBJECTIVE: The purpose of this study was to describe, qualitatively the use of service dogs by persons with physical disabilities and the meaning of this experience. METHOD: Five service dog owners were observed and interviewed on multiple occasions through an ethnographic approach. RESULTS: Identified themes were increased community participation, "closer than family" increased social contact, personal skill development, having fun, responsibility, adjustment, challenges, independence, "someone to watch over me," and "feel like an able-bodied person." CONCLUSION: Service dogs are used to enhance independence in occupational performance areas and contribute to improvements in psychosocial functioning. Given these benefits, service dogs could be viewed as a form of assistive technology that occupational therapists may want to consider as an alternative to traditional devices for some clients.