Prenatal visual experience induces postnatal motor laterality in Japanese quail chicks (Coturnix coturnix japonica).
Species-typical prenatal visual stimulation in avian species is a necessary component in the development of population level lateralized behaviors. This relationship suggests that species-typical developmental outcomes result from organismic and environmental constraints and experiences shared by members of a species. We examined the effects of prenatal visual experience on the development of turning bias and footedness in Japanese quail chicks, a species which does not demonstrate a naturally occurring level of population laterality and only weak individual laterality. Chicks (n=167) were exposed to one of four prenatal conditions: both eye systems exposed to enhanced visual experience, right eye system exposed/left eye system occluded, left eye system exposed/right eye system occluded, or no enhanced visual experience. When subjects were exposed to prenatal visual stimulation, individual and population level laterality was induced. These results suggest that unilateral prenatal visual experience to the right eye or left eye system is sufficient to induce and influence the direction of individual and population laterality in a species that does not normal demonstrate such biases. The results also provide further evidence that prenatal sensory experiences can elicit the development of postnatal lateralization.


Beauty in the eye of the beholder: the two blue opsins of lycaenid butterflies and the opsin gene-driven evolution of sexually dimorphic eyes.
Although previous investigations have shown that wing coloration is an important component of social signaling in butterflies, the contribution of opsin evolution to sexual wing color dichromatism and interspecific divergence remains largely unexplored. Here we report that the butterfly Lycaena rubidus has evolved sexually dimorphic eyes due to changes in the regulation of opsin expression patterns to match the contrasting life histories of males and females. The L. rubidus eye contains four visual pigments with peak sensitivities in the ultraviolet (UV; lambdamax=360 nm), blue (B; lambdamax=437 nm and 500 nm, respectively) and long (LW; lambdamax=568 nm) wavelength range. By combining in situ hybridization of cloned opsin-encoding cDNAs with epi-microspectrophotometry, we found that all four opsin mRNAs and visual pigments are expressed in the eyes in a sex-specific manner. The male dorsal eye, which contains only UV and B (lambdamax=437 nm) visual pigments, indeed expresses two short wavelength opsin mRNAs, UVRh and BRh1. The female dorsal eye, which also has the UV and B (lambdamax=437 nm) visual pigments, also contains the LW visual pigment, and likewise expresses UVRh, BRh1 and LWRh mRNAs. Unexpectedly, in the female dorsal eye, we also found BRh1 co-expressed with LWRh in the R3-8 photoreceptor cells. The ventral eye of both sexes, on the other hand, contains all four visual pigments and expresses all four opsin mRNAs in a non-overlapping fashion. Surprisingly, we found that the 500 nm visual pigment is encoded by a duplicate blue opsin gene, BRh2. Further, using molecular phylogenetic methods we trace this novel blue opsin gene to a duplication event at the base of the Polyommatine+Thecline+Lycaenine radiation. The blue opsin gene duplication may help explain the blueness of blue lycaenid butterflies.


Effectiveness of a simple Internet-based disaster triage educational tool directed toward Latin-American EMS providers.
A previous survey demonstrated a lack of standardization related to disaster triage among Latin-American providers. To assess the effectiveness of a short Internet-based educational intervention in disaster and mass-casualty triage. Using three Spanish Internet emergency medical services (EMS) forums, Latin-American providers were invited to participate in the study. The tool consisted of two educational modules: an introduction to disaster triage module and a START (simple triage and rapid treatment) module. Pre- and post-intervention tests were administered, each consisting of five standardized scenarios. Factorial analysis was used to measure the weight of each scenario. The first and fifth scenarios were identical for intraclass correlation. Skill retention was assessed through a one-month follow-up survey. Statistical analysis was performed using chi-square and Fisher's exact test. A total of 55 EMS providers participated in the study. Five of 55 (9.1%) participants correctly answered four or more scenarios on the pretest intervention, compared with 53 of 55 (96.4%) on the posttest [p < 0.001, relative risk 10.60 (95% CI 4.59-24.49)]. Similar findings were obtained for those accurately triaging all five scenarios, with zero of 55 (0%) in the pretest compared with 49 of 55 in the posttest (p < 0.001). Follow-up at one month was 69%. Four or more scenarios were correctly answered at follow-up by 34 of 38 (89.5%) respondents. No significant difference was noted compared with the immediate post-course survey (p = 0.18). Although initial ability of the cohort to accurately triage patients was suboptimal, a short Internet-based educational tool significantly impacted the cohort's ability to perform triage in a simulated patient environment. This improvement was maintained after one month.


Is enflurane hepatotoxic?
We evaluated 88 cases of hepatic injury that followed, and were attributed to, enflurane anesthesia. In 30 of the cases, data were insufficient to assess the role of enflurane vs other variables as causal factors. In 43 ("unlikely") patients, factors known to produce hepatic injury were clearly present; in the remaining 15 ("possible"), such factors were not evident. No consistent pathologic change was found in liver specimens from either the unlikely or the possible group of cases. A syndrome suggested to be associated with enflurane-induced hepatic injury was present in both groups and did not differ between groups. We conclude that the data do not demonstrate a causal relationship between enflurane anesthesia and subsequent liver injury and that if severe injury is caused by enflurane anesthesia, it is an extremely rare event.


Nursing Graduates' Preparedness for Practice: Substantiating the Call for Competency-Evaluated Nursing Education.
Practice readiness continues to be a challenge in healthcare. This was especially evident during the COVID-19 pandemic. This focused descriptive-correlational study examined nurses' perceived preparedness for practice during the pandemic. One hundred and eighty-four registered nurses (RN) responded to Qualtrics survey questions addressing the competencies they perceived they had and the competencies they felt they needed that would have better prepared them to care for patients during the COVID-19 pandemic. The results demonstrated that although these nurses felt competent in certain areas, they perceived that they needed more education in those same areas to feel better prepared. Bivariate correlations and linear regression analysis indicated that institutional competency development, education, and work experience influenced perceived competency.


Urinary continence after radical prostatectomy: the patient perspective.
To compare the commonly used 0-1 pad definition of urinary continence for postoperative functional outcome after radical prostatectomy and the correlation with self-reported urinary continence and to determine whether a patient questionnaire can deliver more accurate continence status rates. We evaluated a cohort of 873 men who underwent radical prostatectomy (RP) at the General Hospital in Vienna between 1998 and 2006. Patients were surveyed with a questionnaire regarding their postoperative outcome and postoperative urinary incontinence. Baseline and pathological factors were examined to determine whether or not they had an impact on the continence status. A total of 65.2% of men (n = 337) reported themselves to be continent, in contrast 85.1% were continent if the pad definition was applied. Of those using no pads, 93.4% considered themselves continent, while 24.5% of patients using one pad/day did. Overall, 86.5%, 9.8% and 3.7% of continent patients regained continence within 6 months, 6 to 12 months and after 1 year of RP, respectively. A total of 71.5% of men under 65 years old reported full urinary continence, while only 57.0% of men older than 65 considered themselves continent. Men < 65 years recovered full urinary control significantly faster than men older than 65 years- 3.6 versus 4.7 months. Neurovascular bundle resection has a negative effect on continence. The ultimate continence status should be measured with self-administered disease specific questionnaires at 24 months after RP, as it differs from standard physician reported methods. Age and neurovascular bundle resection are variables affecting continence. We believe that patients' subjective reports of their continence are crucial and that multiple outcomes should be objectively measured. Therefore we suggest that validated questionnaires dealing with the patients' perspective postoperatively should be included in routine follow up.


Development of hydrophilic nanocarriers for the charged form of the local anesthetic articaine.
One of the current challenges in drug encapsulation concerns the development of carrier systems for hydrophilic compounds. Potential carriers include nanocapsules prepared with amphiphilic polymers, which consist of a polymeric coating surrounding an aqueous nucleus, or dense matrices such as nanospheres of alginate/chitosan, where the drug may be dispersed in the matrix or adsorbed on the surface. The development of new formulations of nanocarriers, for example the poly(ethylene glycol)-poly(ɛ-caprolactone) (PEG-PCL) nanocapsules and alginate/chitosan (AG/CS) nanospheres described in this work, is needed in the case of ionized drugs such as articaine. This amino amide local anesthetic is the drug of choice in dentistry for regional anesthesia as well as the relief of acute and chronic pain. Here, the physico-chemical properties of suspensions of the nanoparticles (considering diameter, polydispersion, and zeta potential) were determined as a function of time, in order to establish the stability of the systems. The formulations did not show any substantial changes in these parameters, and were stable for up to 120 days of storage at ambient temperature. Satisfactory encapsulation efficiencies were obtained for the PEG-PCL nanocapsules (60%) and the AG/CS nanospheres (45%). Cytotoxicity assays confirmed that the encapsulation of articaine reduced its toxicity, relative to the free drug. The most promising results were obtained using the vesicular system (PEG-PCL nanocapsules), which not only altered the release profile of the drug, but also resulted in the lowest toxicity. This carrier system therefore holds promise for use in future practical applications.


Local, transient tensile stress on the nuclear membrane causes membrane rupture.
Cancer cell migration through narrow constrictions generates compressive stresses on the nucleus that deform it and cause rupture of nuclear membranes. Nuclear membrane rupture allows uncontrolled exchange between nuclear and cytoplasmic contents. Local tensile stresses can also cause nuclear deformations, but whether such deformations are accompanied by nuclear membrane rupture is unknown. Here we used a direct force probe to locally deform the nucleus by applying a transient tensile stress to the nuclear membrane. We found that a transient (∼0.2 s) deformation (∼1% projected area strain) in normal mammary epithelial cells (MCF-10A cells) was sufficient to cause rupture of the nuclear membrane. Nuclear membrane rupture scaled with the magnitude of nuclear deformation and the magnitude of applied tensile stress. Comparison of diffusive fluxes of nuclear probes between wild-type and lamin-depleted MCF-10A cells revealed that lamin A/C, but not lamin B2, protects the nuclear membranes against rupture from tensile stress. Our results suggest that transient nuclear deformations typically caused by local tensile stresses are sufficient to cause nuclear membrane rupture.


Adding Rapid-Acting Insulin or GLP-1 Receptor Agonist to Basal Insulin: Outcomes in a Community Setting.
To evaluate real-world outcomes in patients with type 2 diabetes mellitus (T2DM) receiving basal insulin who initiate add-on therapy with a rapid-acting insulin (RAI) or a glucagon-like peptide 1 (GLP-1) receptor agonist. Data were extracted retrospectively from a U. S. health claims database. Adults with T2DM on basal insulin who added an RAI (basal + RAI) or GLP-1 receptor agonist (basal + GLP-1) were included. Propensity score matching (with a 1 up to 3 ratio) was used to control for differences in baseline demographics, clinical characteristics, and health resource utilization. Endpoints included prevalence of hypoglycemia, pancreatic events, all-cause and diabetes-related resource utilization, and costs at 1-year follow-up. Overall, 6,718 matched patients were included: 5,013 basal + RAI and 1,705 basal + GLP1. Patients in both groups experienced a similar proportion of any hypoglycemic event (P = .4079). Hypoglycemic events leading to hospitalization were higher in the basal + RAI cohort (2.7% vs. 1.8%; P = .0444). The basal + GLP-1 cohort experienced fewer all-cause (13.55% vs. 18.61%; P<.0001) and diabetes-related hospitalizations (11.79% vs. 15.68%; P<.0001). The basal + GLP-1 cohort had lower total all-cause health care costs ($18,413 vs. $20,821; P = .0002) but similar diabetes-related costs ($9,134 vs. $8,985; P<.0001) compared with the basal + RAI cohort. Add-on therapy with a GLP-1 receptor agonist in T2DM patients receiving basal insulin was associated with fewer hospitalizations and lower total all-cause costs compared with add-on therapy using an RAI and could be considered as an alternative to an RAI in certain patients with T2DM who do not achieve effective glycemic control with basal insulin.


IFNL4 and IFNL3 associated polymorphisms strongly influence the spontaneous IFN-alpha receptor-1 expression in HCV-infected patients.
Single-nucleotide polymorphism in IFNL3 gene (rs12979860) predicts spontaneous and therapy-induced HCV clearance. In a previous study from our group PBMC from patients with favourable rs12979860 genotype showed higher levels of IFNAR-1 mRNA. Recently, a dinucleotide polymorphism, ss469415590 (TT or ΔG), has been discovered in the region upstream IFNL3 gene, which is in high linkage disequilibrium with rs12979860. ss469415590[ΔG] is a frameshift variant that creates a novel gene, designed IFNL4, encoding the interferon-lambda 4 protein (IFNL4). The aim of the present study was to extend the analysis of IFNAR-1 mRNA levels to the ss469415590 variants. Our results highlight that the difference of IFNAR-1 mRNA levels between favourable and unfavourable genotype combinations, at both rs12979860 and ss469415590 loci, is stronger than that observed for single polymorphisms at each locus. These findings suggest may represent the biological basis for the observed association between IFNL3 CC and IFNL4 TT/TT genotypes and favourable outcome of either natural HCV infection (clearance vs chronic evolution) or IFN-based therapy.


Uroporphyrinogen 3 cosynthetase in human congenital erythropoietic porphyria.
Activity of the enzyme uroporphyrinogen III cosynthetase in hemolysates from five patients with congenital erythropoietic porphyria was much lower than the activity in control samples. The low cosynthetase activity in patients was not due to the presence of a free inhibitor or some competing enzymatic activity, because hemolysates from porphyric subjects did not interfere either with the cosynthetase activity of hemolysates from normal subjects or with cosynthetase prepared from hematopoietic mouse spleen. This partial deficiency of cosynthetase in congenital erythropoietic porphyria corresponds to that shown previously in the clinically similar erythropoietic porphyria of cattle and explains the overproduction of uroporphyrin I in the human disease.


Expression of vasoactive intestinal peptide receptor messenger RNA in the hypothalamus and pituitary throughout the turkey reproductive cycle.
Vasoactive intestinal peptide (VIP) has been implicated in the regulation of avian reproductive activity and appears to act at the level of the hypothalamus and pituitary. This in situ hybridization histochemistry study describes the distribution of VIP receptor mRNA expression in the hypothalamus and the pituitary of reproductively active (laying) and quiescent (nonphotostimulated, incubating, and photorefractory) female turkeys and characterizes the differences observed in VIP receptor gene expression. VIP receptor mRNA, while expressed throughout the hypothalamus, was specifically expressed in areas known to contain GnRH-I neurons in the chicken, i.e., the lateral septum, medial preoptic area, anterior hypothalamus, and paraventricular nucleus. Significant differences in VIP receptor mRNA expression between different reproductive states was observed only within the infundibular nuclear complex. VIP receptor mRNA was markedly less in nonphotostimulated and photorefractory hens as compared with laying and incubating hens. The most dense VIP receptor mRNA was found in the anterior pituitary, where it was 2.4- and 3.0-fold greater in laying and incubating hens, respectively, as compared with that in nonphotostimulated ones. Hens that stopped incubating and became photorefractory displayed pituitary VIP receptor mRNA levels similar to those of nonphotostimulated birds. The changes in pituitary VIP receptor mRNA expression were positively correlated with known changes in pituitary prolactin (PRL) mRNA expression and PRL content and release. These findings indicate that the variations in PRL secretion observed across the turkey reproductive cycle are, in part, regulated by changes in VIP receptors at the pituitary level.


The clouded crystal ball: a 35-year follow-up of psychiatrists' predictions.
In 1946-1949 psychiatrists examined in depth more than 200 students from four first-year medical school classes and predicted their future adjustment. Judging by the former students' replies to a questionnaire in 1981-1982, the psychiatrists' favorable predictions were for the most part borne out, whereas the unfavorable predictions were much less likely to have been realized. The psychiatrists appeared to have overemphasized the significance of the psychopathology they discovered and to have underestimated the potential of many of these young adults for spontaneous personality change.


Five-year incidence of type 2 diabetes mellitus among cardiovascular disease-free Greek adults: findings from the ATTICA study.
We evaluated the 5-year incidence of diabetes in an adult population from Greece. 3042 individuals (>18 years), free of cardiovascular disease, participated in the baseline examination (during 2001-2002). Of this sample, 1012 men and 1035 women were found alive at the time of follow-up, while 32 (2.1%) men and 22 (1.4%) women died during this period. The rest were lost to follow-up. Incidence of type 2 diabetes mellitus was evaluated in 1806 participants who did not have diabetes at baseline. The age-adjusted 5-year incidence of diabetes was 5.5% (men, 5.8%; women, 5.2%). A linear trend was observed between diabetes incidence and age (5.6% increases in incidence per 1-year difference in age, p<0.001). Multiple logistic regression analysis revealed that age (OR per 1 yr=1.04, 95% CI 1.02-1.06), waist (OR per 1 cm=1.02, 95% CI 1.01-1.003), physical activity (OR=0.62, 95% CI 0.35-1.02) and family history of diabetes (OR=2.65, 95% CI 1.58-4.53), as well as fasting glucose levels (OR per 1 mg/dl=1.05, 95% CI 1.03-1.07), were the most significant baseline predictors for diabetes, after adjusting for various potential confounders. Additionally, presence of metabolic syndrome at baseline evaluation 2.95-fold the risk of diabetes (95% CI 1.89-4.61), and showed better classification ability than the model that contained the components of the syndrome (ie, correct classification rate: 94.5% vs. 92.3%). Our findings show that a 5.5% incidence rate of diabetes within a 5-year period, which suggests that the prevalence of this disorder in Greece is rising. Aging, heredity, and metabolic syndrome were the most significant determinants of diabetes.


Reward prediction error signaling in posterior dorsomedial striatum is action specific.
Neural correlates of reward prediction errors (RPEs) have been found in dorsal striatum. Such signals may be important for updating associative action representations within striatum. In order that the appropriate representations can be updated, it might be important for the RPE signal to be specific for the action that led to that error. However, RPEs signaled by midbrain dopamine neurons, which project heavily to striatum, are not action-specific. Here we tested whether RPE-like activity in dorsal striatum is action-specific; we recorded single-unit activity in posterior dorsomedial and dorsolateral striatum as rats performed a task in which the reward predictions associated with two different actions were repeatedly violated, thereby eliciting RPEs. We separately analyzed fast firing neurons (FFNs) and phasically firing neurons (total n = 1076). Only among FFNs recorded in posterior dorsomedial striatum did we find a population with RPE-like characteristics (19 of all 196 FFNs, 10%). This population showed a phasic increase in activity during unexpected rewards, a phasic decrease in activity during unexpected omission of rewards, and a phasic increase in activity during cues when they predicted high-value reward. However, unlike a classical RPE signal, this signal was linked to the action that elicited the prediction error, in that neurons tended to signal RPEs only after their anti-preferred action. This action-specific RPE-like signal could provide a mechanism for updating specific associative action representations in posterior dorsomedial striatum.


Reciprocal selection causes a coevolutionary arms race between crossbills and lodgepole pine.
Few studies have shown both reciprocal selection and reciprocal adaptations for a coevolving system in the wild. The goal of our study was to determine whether the patterns of selection on Rocky Mountain lodgepole pine (Pinus contorta spp. latifolia) and red crossbills (Loxia curvirostra complex) were concordant with earlier published evidence of reciprocal adaptations in lodgepole pine and crossbills on isolated mountain ranges in the absence of red squirrels (Tamiasciurus hudsonicus). We found that selection (directional) by crossbills on lodgepole pine where Tamiasciurus are absent was divergent from the selection (directional) exerted by Tamiasciurus on lodgepole pine. This resulted in divergent selection between areas with and without Tamiasciurus that was congruent with the geographic patterns of cone variation. In the South Hills, Idaho, where Tamiasciurus are absent and red crossbills are thought to be coevolving with lodgepole pine, crossbills experienced stabilizing selection on bill size, with cone structure as the agent of selection. These results show that crossbills and lodgepole pine exhibit reciprocal adaptations in response to reciprocal selection, and they provide insight into the traits mediating and responding to selection in a coevolutionary arms race.


Plantar Fasciitis: Diagnosis and Conservative Management.
Plantar fasciitis is a common cause of heel pain, which frustrates patients and practitioners alike because of its resistance to treatment. It has been associated with obesity, middle age, and biomechanical abnormalities in the foot, such as tight Achilles tendon, pes cavus, and pes planus. It is considered to be most often the result of a degenerative process at the origin of the plantar fascia at the calcaneus. However, neurogenic and other causes of subcalcaneal pain are frequently cited. A combination of causative factors may be present, or the true cause may remain obscure. Although normally managed with conservative treatment, plantar fasciitis is frequently resistant to the wide variety of treatments commonly used, such as nonsteroidal anti-inflammatory drugs, rest, pads, cups, splints, orthotics, corticosteroid injections, casts, physical therapy, ice, and heat. Although there is no consensus on the efficacy of any particular conservative treatment regimen, there is agreement that nonsurgical treatment is ultimately effective in approximately 90% of patients. Since the natural history of plantar fasciitis has not been established, it is unclear how much of symptom resolution is in fact due to the wide variety of commonly used treatments.


Measurement of photosystem I activity with photoreduction of recombinant flavodoxin.
Flavodoxin can function as an alternative electron acceptor for photosystem I (PSI) in place of ferredoxin under iron-limiting conditions. The isiB gene, encoding the flavodoxin in Synechococcus sp. PCC 7002, was overexpressed in Escherichia coli. Under the conditions employed, most recombinant flavodoxin (rFlvd) was in soluble form with cofactor correctly inserted. The absorption spectrum of rFlvd was identical to that of the native flavodoxin of the cyanobacteria. Photoreduction of rFlvd by PSI particles and thylakoid membranes was determined directly by monitoring the absorption change at 467 nm. The optimal conditions for rFlvd photoreduction were determined. Compared to other methods currently employed to measure PSI activity such as oxygen uptake in the presence of methyl viologen and NADP+ photoreduction in the presence of ferredoxin and ferredoxin:NADP+ oxidoreductase, measurement of PSI activity with flavodoxin as an electron acceptor has several advantages. It measures the full-chain electron transfer chain of PSI since flavodoxin accepts electrons from FA/FB and it is much simpler than the method with NADP+ photoreduction. With this method, we found that the affinity of wild-type PSI for rFlvd was 35% higher than that of the PsaE-less PSI, showing that this method is sensitive to structural changes of PSI. Our results demonstrate that rFlvd photoreduction is an effective and simple method for PSI activity measurement.


Malondialdehyde and protein carbonyl as biomarkers for oxidative stress and disease progression in patients with chronic myeloid leukemia.
Oxidative stress, a pervasive condition of an increased amount of free radicals, is now recognized to be prominent feature of various diseases and their progression. However, evidence for this association has often been lacking because of a lack of specific biomarkers and methods available to evaluate oxidative stress status in humans with disease conditions. Emphasis is now being placed on biomarkers of oxidative stress, which can be objectively measured and evaluated as indicators of normal biological and pathogenic processes. The aim of this study was to investigate the plasma levels of malondialdehyde (MDA) and protein carbonyl (PC) as biomarkers for oxidative stress and disease progression in patients with chronic myeloid leukemia (CML). The study included 20 CML patients and 10 age-and sex-matched healthy control volunteers. The mean age of CML patients was 37.11+/-11.36 years and that of controls was 31.07+/-7.60 years. There was a significant increase (p<0.05) in plasma MDA and PC levels in CML patients as compared to healthy volunteers. Our results also showed that plasma MDA and PC levels were significantly higher (p<0.001) in both chronic phase (CML-CP) and accelerated phase (CML-AP) as compared to healthy volunteers. During the follow-up of 12 months, two patients of CML-CP progressed to the accelerated phase. The mean plasma levels of MDA and PC in patients with CML-CP who progressed to CML-AP were found to be higher than in patients with CML-CP who did not progress to the accelerated phase. Plasma MDA and PC appears to reflect the oxidative stress status and disease progression in CML and can be used as biomarkers for oxidative stress and disease progression.


Synergistic interactions between carotene ring hydroxylases drive lutein formation in plant carotenoid biosynthesis.
Plant carotenoids play essential roles in photosynthesis, photoprotection, and as precursors to apocarotenoids. The plastid-localized carotenoid biosynthetic pathway is mediated by well-defined nucleus-encoded enzymes. However, there is a major gap in understanding the nature of protein interactions and pathway complexes needed to mediate carotenogenesis. In this study, we focused on carotene ring hydroxylation, which is performed by two structurally distinct classes of enzymes, the P450 CYP97A and CYP97C hydroxylases and the nonheme diiron HYD enzymes. The CYP97A and HYD enzymes both function in the hydroxylation of β-rings in carotenes, but we show that they are not functionally interchangeable. The formation of lutein, which involves hydroxylation of both β- and ε-rings, was shown to require the coexpression of CYP97A and CYP97C enzymes. These enzymes were also demonstrated to interact in vivo and in vitro, as determined using bimolecular fluorescence complementation and a pull-down assay, respectively. We discuss the role of specific hydroxylase enzyme interactions in promoting pathway flux and preventing the formation of pathway dead ends. These findings will facilitate efforts to manipulate carotenoid content and composition for improving plant adaptation to climate change and/or for enhancing nutritionally important carotenoids in food crops.


The colovescical fistula in diverticular disease: Laparoscopic approach in two different cases.
The colovescical fistula is one of the complications of diverticular disease. It can cause significant symptoms like pneumaturia and fecaluria affecting the quality of life and sometimes leading to death, usually secondary to sepsis. We describe two cases of colovescical fistula treated by laparoscopic approach in patients with diagnosis of complicated acute diverticulitis. We studied two patients with clinical, radiological and endoscopic diagnosis of colovescical fistula as a consequence of diverticular disease. We performed a totally laparoscopic treatment with colonic resection and colo-proctoanastomosis after the closure of the fistula with intracorporeal sutures. Colovescical fistula should be suspected in patients who present fever with persistent dysuria, pneumaturia or fecaluria. The diagnosis is confirmed by a CT abdominal scan, a colonoscopy in order to rule out a colon cancer and a cystoscopy to assess the grade of bladder involvement. Although colovescical fistulas caused by diverticular disease were once considered a contraindication to laparoscopic resection, nowadays they are increasingly treated by experienced surgeons using laparoscopic techniques. Compared with laparoscopic surgery for uncomplicated diverticulitis the mini-invasive treatment of colovescical fistulas requires a longer operative time and advanced surgical skills.


Experts reviews of the multidisciplinary consensus conference colon and rectal cancer 2012: science, opinions and experiences from the experts of surgery.
The first multidisciplinary consensus conference on colon and rectal cancer was held in December 2012, achieving a majority of consensus for diagnostic and treatment decisions using the Delphi Method. This article will give a critical appraisal of the topics discussed during the meeting and in the consensus document by well-known leaders in surgery that were involved in this multidisciplinary consensus process. Scientific evidence, experience and opinions are collected to support multidisciplinary teams (MDT) with arguments for medical decision-making in diagnosis, staging and treatment strategies for patients with colon or rectal cancer. Surgery is the cornerstone of curative treatment for colon and rectal cancer. Standardizing treatment is an effective instrument to improve outcome of multidisciplinary cancer care for patients with colon and rectal cancer. In this article, a review of the following focuses; Perioperative care, age and colorectal surgery, obstructive colorectal cancer, stenting, surgical anatomical considerations, total mesorectal excision (TME) surgery and training, surgical considerations for locally advanced rectal cancer (LARC) and local recurrent rectal cancer (LRRC), surgery in stage IV colorectal cancer, definitions of quality of surgery, transanal endoscopic microsurgery (TEM), laparoscopic colon and rectal surgery, preoperative radiotherapy and chemoradiotherapy, and how about functional outcome after surgery?


Prospective study of aspirin use and risk of stroke in women.
In secondary prevention, aspirin reduces risk of ischemic stroke. In primary prevention of stroke, however, the role of aspirin is uncertain, especially in women. In 1980, 79 319 women in the Nurses' Health Study cohort, 34 to 59 years of age and free of diagnosed cardiovascular disease, cancer, and rheumatoid arthritis, completed questionnaires that included information on aspirin use. Data on aspirin use were updated in 1982, 1984, and 1988. By 1994, after 994 231 person-years of follow-up, 503 incident strokes (295 ischemic strokes, 100 subarachnoid hemorrhages, 52 intraparenchymal hemorrhages, and 56 strokes of undetermined type) were documented. There was no clear relationship between aspirin use and risk of total stroke; risk was slightly reduced among women who took 1 to 6 aspirin per week and slightly increased among women who took 7 or more aspirin per week. Women who took 1 to 6 aspirin per week had a lower risk of large-artery occlusive infarction compared with women who reported no aspirin use; after simultaneous adjustment for other cardiovascular risk factors and selected nutrients, the multivariate relative risk was 0.50 (95% CI 0.29 to 0.85, P=0.01). Women who took 15 or more aspirin per week had an excess risk of subarachnoid hemorrhage; the multivariate relative risk was 2.02 (95% CI 1.04 to 3.91, P for trend=0.02). The reduction in large-artery occlusive infarction with aspirin was of greater magnitude for older, hypertensive, or smoking women than for younger, nonhypertensive, or nonsmoking women; the elevation in subarachnoid hemorrhage with aspirin was also more apparent for older or hypertensive women than for younger or nonhypertensive women. Aspirin use was not associated with risk of other subtypes of stroke. These prospective data indicate that women who take 1 to 6 aspirin per week have a reduced risk of large-artery occlusive infarction, but those who use 15 or more aspirin per week have an increased risk of subarachnoid hemorrhage. This observational study suggests benefits of aspirin for ischemic stroke with low frequency of use and hazards for hemorrhagic stroke with high frequency of use, particularly among older or hypertensive women. Thus, the effect on total stroke will depend on the dose of aspirin and the distribution of stroke subtypes and risk factors in the population.


Effects of 5'-uridylic acid feeding on postprandial plasma concentrations of metabolites and metabolic hormones in pre-weaning goats.
5'-Uridylic acid (UMP), which is present at high concentrations in cow's colostrum, has been shown to cause a reduction in increased plasma levels of insulin and glucose after ingestion of milk replacer in pre-weaning calves. However, the precise mechanisms of UMP action have not been investigated, and its action has not been investigated in other pre-weaning ruminants. In order to demonstrate whether UMP causes changes in postprandial metabolic and hormonal parameters in pre-weaning goats, 11 Saanen kids were given milk replacer (twice a day) without (n = 5) or with (n = 6) UMP (1 g for each meal, 2 g/day for each head) for 14 days. Analysis of blood samples taken in the morning of day 14 demonstrated that the feeding of milk replacer with UMP abolished the significant changes in postprandial plasma glucose, NEFA, GH and insulin concentrations induced by feeding of milk replacer alone, and demonstrated a tendency to increase IGF-I levels. However, there was no significant difference between the two groups at any sampling time. We conclude that UMP feeding with milk replacer showed a tendency to blunt the postprandial changes in levels of some plasma metabolites and hormones that are induced by replacer alone in pre-weaning goats.


MiR-200c/FUT4 axis prevents the proliferation of colon cancer cells by downregulating the Wnt/β-catenin pathway.
MicroRNA (miR)-200c has been widely reported to be involved in colon cancer progress. However, the mechanisms of miR-200c in regulating tumor metastasis and growth remain to be fully elucidated. This study aimed to investigate the mechanism of miR-200c targets fucosyltransferase 4 (FUT4) on the proliferation of colon cancer. The miR-200c and FUT4 mRNA levels in LoVo and SW480 cells were measured by real-time quantitative polymerase chain reaction. Further, miR-200c mimic, FUT4 siRNA and FUT4 mimic were transfected into cells, separately. Cell counting kit-8, plate colony formation and transwell assays were used to analyse the cells biological behaviour.. Immunofluorescence was used to analyse the Ki-67 expression Moreover, the Wnt/β-catenin pathway-related proteins were detected by western blots. A double luciferase experiment was performed to confirm the relationship between miR-200c and FUT4. In vivo, tumour growth and Wnt/β-catenin pathway-related proteins were also analysed. In vitro, the expression of miR-200c and FUT4 were negatively correlated in LoVo and SW480 cells (correlation coefficients were - 0.9046 and - 0.9236, respectively). MiR-200c overexpression inhibited the proliferation, migration and invasion of LoVo and SW480 cells by downregulating FUT4. The Ki67-positive cells and Wnt/β-catenin signalling pathway-related proteins were reduced in the miR-200c overexpression and FUT4 silencing groups. A dual luciferase reporting system identified FUT4 as the target of miR-200c. The results in vivo were further confirmed the foundation of cells study. In summary, miR-200c overexpression inhibits proliferation of colon cancer targeting FUT4 to downregulate the Wnt/β-catenin pathway, which promises molecular targets to inhibit metastasis for colon cancer therapy.


Longitudinal analysis of the behavioral phenotype in a novel transgenic rat model of early stages of Alzheimer's disease.
Intraneuronal accumulation of amyloid β (iAβ) has been linked to mild cognitive impairment that may precede Alzheimer's disease (AD) onset. This neuropathological trait was recently mimicked in a novel animal model of AD, the hemizygous transgenic McGill-R-Thy1-APP (Tg(+/-)) rat. The characterization of the behavioral phenotypes in this animal model could provide a baseline of efficacy for earlier therapeutic interventions. The aim of the present study was to undertake a longitudinal study of Aβ accumulation and a comprehensive behavioral evaluation of this transgenic rat model. We assessed exploratory activity, anxiety-related behaviors, recognition memory, working memory, spatial learning and reference memory at 3, 6, and 12 months of age. In parallel, we measured Aβ by ELISA, Western blots and semiquantitative immunohistochemistry in hippocampal samples. SDS-soluble Aβ peptide accumulated at low levels (~9 pg/mg) without differences among ages. However, Western blots showed SDS-resistant Aβ oligomers (~30 kDa) at 6 and 12 months, but not at 3 months. When compared to wild-type (WT), male Tg(+/-) rats exhibited a spatial reference memory deficit in the Morris Water Maze (MWM) as early as 3 months of age, which persisted at 6 and 12 months. In addition, Tg(+/-) rats displayed a working memory impairment in the Y-maze and higher anxiety levels in the Open Field (OF) at 6 and 12 months of age, but not at 3 months. Exploratory activity in the OF was similar to that of WT at all-time points. Spatial learning in the MWM and the recognition memory, as assessed by the Novel Object Recognition Test, were unimpaired at any time point. The data from the present study demonstrate that the hemizygous transgenic McGill-R-Thy1-APP rat has a wide array of behavioral and cognitive impairments from young adulthood to middle-age. The low Aβ burden and early emotional and cognitive deficits in this transgenic rat model supports its potential use for drug discovery purposes in early AD.


An exploration of lesbian maternal bereavement.
Research on parental bereavement has focused historically on single or partnered cross-gendered (heterosexual) bereaved parents. No previous studies have examined the unique experiences of same-gendered bereaved parents. This multiple-case study focused on child death in same-gendered-parent families. The goal of this study was to yield information that will expand the existing body of knowledge regarding parental bereavement and add to the scant literature on lesbian parenthood and the challenges that lesbians may face as a marginalized group. The study used in-depth interviews with six self-identified lesbian mothers who had experienced the death of a child at various ages and from various causes. Results suggest that lesbian bereaved mothers experience a type of double-disenfranchisement after their losses and that social support is often insufficient to meet their psychological needs. Because previous research has not been published on this specific population, the findings may be worthwhile for the lesbian and gay parenting community, community advocacy groups, and the clinicians who serve them.


Job strain and risk indicators for cardiovascular disease in young female nurses.
This study examined the possible effects of job demands, decision latitude, and job-related social support on risk indicators for cardiovascular disease (CVD) in 165 female nurses. Job strain was measured with the Job Content Questionnaire; CVD risk was measured with insulin, total cholesterol, triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), fibrinogen, tissue-type plasminogen activator (tPA) antigen, tPA activity, plasminogen activator inhibitor-1 antigen, and blood pressure. Multivariate analysis of covariance and regression analyses revealed no effects of either job strain or social support on these risk indicators. All risk indicators deteriorated with age and body mass index. Oral contraceptive use improved fibrinolytic potential and increased HDL-C but had adverse effects on TG levels. Results suggest that in healthy young women job strain is not associated with an unfavorable metabolic or fibrinolytic risk profile.


Polycystic Kidney Disease without an Apparent Family History.
The absence of a positive family history (PFH) in 10%-25% of patients poses a diagnostic challenge for autosomal dominant polycystic kidney disease (ADPKD). In the Toronto Genetic Epidemiology Study of Polycystic Kidney Disease, 210 affected probands underwent renal function testing, abdominal imaging, and comprehensive PKD1 and PKD2 mutation screening. From this cohort, we reviewed all patients with and without an apparent family history, examined their parental medical records, and performed renal imaging in all available parents of unknown disease status. Subsequent reclassification of 209 analyzed patients revealed 72.2% (151 of 209) with a PFH, 15.3% (32 of 209) with de novo disease, 10.5% (22 of 209) with an indeterminate family history, and 1.9% (four of 209) with PFH in retrospect. Among the patients with de novo cases, we found two families with germline mosaicism and one family with somatic mosaicism. Additionally, analysis of renal imaging revealed that 16.3% (34 of 209) of patients displayed atypical PKD, most of which followed one of three patterns: asymmetric or focal PKD with PFH and an identified PKD1 or PKD2 mutation (15 of 34), asymmetric and de novo PKD with proven or suspected somatic mosaicism (seven of 34), or focal PKD without any identifiable PKD1 or PKD2 mutation (eight of 34). In conclusion, PKD without an apparent family history may be due to de novo disease, missing parental medical records, germline or somatic mosaicism, or mild disease from hypomorphic PKD1 and PKD2 mutations. Furthermore, mutations of a newly identified gene for ADPKD, GANAB, and somatic mosaicism need to be considered in the mutation-negative patients with focal disease.


Recent advances in molecular imprinting technology: current status, challenges and highlighted applications.
Molecular imprinting technology (MIT) concerns formation of selective sites in a polymer matrix with the memory of a template. Recently, molecularly imprinted polymers (MIPs) have aroused extensive attention and been widely applied in many fields, such as solid-phase extraction, chemical sensors and artificial antibodies owing to their desired selectivity, physical robustness, thermal stability, as well as low cost and easy preparation. With the rapid development of MIT as a research hotspot, it faces a number of challenges, involving biological macromolecule imprinting, heterogeneous binding sites, template leakage, incompatibility with aqueous media, low binding capacity and slow mass transfer, which restricts its applications in various aspects. This critical review briefly reviews the current status of MIT, particular emphasis on significant progresses of novel imprinting methods, some challenges and effective strategies for MIT, and highlighted applications of MIPs. Finally, some significant attempts in further developing MIT are also proposed (236 references).


[Endovascular and surgical treatment of a patient with traumatic rupture of the aorta and hepatic artery].
Traumatic rupture of the aorta is the second most common cause of death in closed chest injury. The latest findings of autopsy showed that 80% of lethal outcomes in aortic injury occur in the prehospital period. Taking into consideration the incidence and high rate of death prior to the diagnosis stage, aortic rupture in closed thoracic injury is an important problem. Due to the characteristic mechanism of the development (during sharp deceleration of the body) this type of traumatic lesion of the aorta became known as "deceleration syndrome". The most vulnerable to tension aortic portion is its neck where the mobile part of the thoracic aorta is connected to the fixed arch in the place of the arterial ligament attachment. Open surgical intervention in patients with severe closed chest injury (often concomitant injury) is associated with high mortality and complications. Currently endovascular prosthetic repair of the aorta is a method of choice at the primary stage of treatment of patients with aortic injury. In this article we present a rare case report of concomitant lesion of large vessels (the descending aortic portion and proper hepatic artery) in a patient with severe concomitant injury, as well as peculiarities of diagnosis and combined treatment (endovascular prosthetic repair of the aorta and hepatic artery with an aotovein).


Nectar Analysis Throughout the Genus Nicotiana Suggests Conserved Mechanisms of Nectar Production and Biochemical Action.
We have evaluated the floral nectars of nine species from different sections of the genus Nicotiana. These nine species effectively cover the genus. We found that the nectary glands from these different species showed similar developmental regulation with swelling of nectaries during the first half of development and a distinct color change in the nectary gland as development approaches anthesis. When we examined the composition of the nectar from these nine different species we found that they were similar in content. Carbohydrate compositions of these various nectars varied between these species with N. bonariensis showing the highest and N. sylvestris lowest level of sugars. Based upon the amount of carbohydrates, the nectars fell into two groups. We found that hydrogen peroxide accumulated in the nectars of each of these species. While all species showed the presence of hydrogen peroxide in nectar, the quantitative amounts of hydrogen peroxide which was very high in N. rustica and N. bonariensis, suggesting be a common characteristic in short flower Nicotiana species. We further found that the antioxidant ascorbate accumulated in nectar and β-carotene accumulated in nectaries. β-carotene was most high in nectaries of N. bonariensis. We also examined the presence of proteins in the nectars of these species. The protein profile and quantities varied significantly between species, although all species have showed the presence of proteins in their nectars. We performed a limited proteomic analysis of several proteins from these nectars and determined that each of the five abundant proteins examined were identified as Nectarin 1, Nectarin 3, or Nectarin 5. Thus, based upon the results found in numerous species across the genus Nicotiana, we conclude that the mechanisms identified are similar to those mechanisms found in previous studies on ornamental tobacco nectars. Further, these similarities are remarkably conserved, throughout the genus Nicotiana.


Comparison of growth characteristics of anaerobic fungi isolated from ruminant and non-ruminant herbivores during cultivation in a defined medium.
Anaerobic fungi were isolated from rumen fluid of a domestic sheep (Ovis aries; a ruminant) and from faeces of five non-ruminants: African elephant (Loxodonta africana), black rhinoceros (Diceros bicornis), Indian rhinoceros (Rhinoceros unicornis), Indian elephant (Elephas maximus) and mara (Dolichotis patagonum). The anaerobic fungus isolated from the sheep was a Neocallimastix species and the isolates from non-ruminants were all species similar to Piromyces spp. A defined medium is described which supported growth of all the isolates, and was used to examine growth characteristics of the different strains. For each fungus the lipid phosphate content was determined after growth on cellobiose and the resulting values were used to estimate fungal biomass after growth on solid substrates. The ability of isolates from ruminants and non-ruminants to digest both wheat straw and cellulose was comparable. More than 90% and 60%, respectively, of filter paper cellulose and wheat straw were digested by most strains within 60-78 h. Growth of two fungi, isolated from rumen fluid of a sheep (Neocallimastix strain N1) and from faeces of an Indian rhinoceros (Piromyces strain R1), on cellobiose was studied in detail. Fungal growth yields on cellobiose were 64.1 g (mol substrate)-1 for N1 and 34.2 g mol-1 for R1. The major fermentation products of both strains were formate, lactate, acetate, ethanol and hydrogen.


Risk factors for erosive reflux esophagitis: a case-control study.
It is presently not fully understood which risk factors contribute to the occurrence of reflux esophagitis and how such factors might influence the severity of the disease. The aim of this study was to delineate the clinical epidemiology of erosive reflux esophagitis. Outpatients from a medicine and gastroenterology clinic who underwent upper GI endoscopy were recruited into a case-control study. A total of 1,533 patients with and 3,428 patients without endoscopically diagnosed reflux esophagitis were categorized as case and control subjects, respectively. Using multivariate logistic regressions for statistical analysis, the presence of esophageal erosions, ulcers or strictures, served as three separate outcome variables. Demographic characteristics, intake of nonsteroidal anti-inflammatory drugs (NSAIDs), consumption of alcohol and cigarettes, and the presence of hiatus hernia or peptic ulcer served as predictor variables. Erosive reflux esophagitis tended to occur more frequently in Caucasian male patients. Hiatus hernia was associated with a strong risk for developing esophageal erosions, ulcers, and strictures. Although statistical significance was demonstrated only for esophageal erosions, in all grades of reflux esophagitis alike, gastric and duodenal ulcer exerted a protective influence. Consumption of NSAIDs increased the risk for esophageal ulcers only. Smoking and alcohol were not associated with an increased risk of developing any type of erosive reflux esophagitis. The results stress the critical role played by hiatus hernia in all grades of erosive reflux esophagitis. NSAIDs may act through a mechanism of topically induced esophageal injury. Our data also suggest that the presence of either gastric or duodenal ulcer exerts a protective influence against the development of reflux disease.


C-F activation of fluorinated arenes using NHC-stabilized nickel(0) complexes: selectivity and mechanistic investigations.
The reaction of [Ni2((i)Pr2Im)4(COD)] 1a or [Ni((i)Pr2Im)2(eta(2)-C2H4)] 1b with different fluorinated arenes is reported. These reactions occur with a high chemo- and regioselectivity. In the case of polyfluorinated aromatics of the type C6F5X such as hexafluorobenzene (X = F) octafluorotoluene (X = CF3), trimethyl(pentafluorophenyl)silane (X = SiMe3), or decafluorobiphenyl (X = C6F5) the C-F activation regioselectively takes place at the C-F bond in the para position to the X group to afford the complexes trans-[Ni((i)Pr2Im)2(F)(C6F5)]2, trans-[Ni((i)Pr2Im)2(F)(4-(CF3)C6F4)] 3, trans-[Ni((i)Pr2Im)2(F)(4-(C6F5)C6F4)] 4, and trans-[Ni((i)Pr2Im)2(F)(4-(SiMe3)C6F4)] 5. Complex 5 was structurally characterized by X-ray diffraction. The reaction of 1a with partially fluorinated aromatic substrates C6H(x)F(y) leads to the products of a C-F activation trans-[Ni((i)Pr2Im)2(F)(2-C6FH4)] 7, trans-[Ni((i)Pr2Im)2(F)(3,5-C6F2H3)] 8, trans-[Ni((i)Pr2Im)2(F)(2,3-C6F2H3)] 9a and trans-[Ni((i)Pr2Im)2(F)(2,6-C6F2H3)] 9b, trans-[Ni((i)Pr2Im)2(F)(2,5-C6F2H3)] 10, and trans-[Ni((i)Pr2Im)2(F)(2,3,5,6-C6F4H)] 11. The reaction of 1a with octafluoronaphthalene yields exclusively trans-[Ni((i)Pr2Im)2(F)(1,3,4,5,6,7,8-C10F7)] 6a, the product of an insertion into the C-F bond in the 2-position, whereas for the reaction of 1b with octafluoronaphthalene the two isomers trans-[Ni((i)Pr2Im)2(F)(1,3,4,5,6,7,8-C10F7)] 6a and trans-[Ni((i)Pr2Im)2(F)(2,3,4,5,6,7,8-C10F7)] 6b are formed in a ratio of 11:1. The reaction of 1a or of 1b with pentafluoropyridine at low temperatures affords trans-[Ni((i)Pr2Im)2(F)(4-C5NF4)] 12a as the sole product, whereas the reaction of 1b performed at room temperature leads to the generation of trans-[Ni((i)Pr2Im)2(F)(4-C5NF4)] 12a and trans-[Ni((i)Pr2Im)2(F)(2-C5NF4)] 12b in a ratio of approximately 1:2. The detection of intermediates as well as kinetic studies gives some insight into the mechanistic details for the activation of an aromatic carbon-fluorine bond at the {Ni((i)Pr2Im)2} complex fragment. The intermediates of the reaction of 1b with hexafluorobenzene and octafluoronaphthalene, [Ni((i)Pr2Im)2(eta(2)-C6F6)] 13 and [Ni((i)Pr2Im)2(eta(2)-C10F8)] 14, have been detected in solution. They convert into the C-F activation products. Complex 14 was structurally characterized by X-ray diffraction. The rates for the loss of 14 at different temperatures for the C-F activation of the coordinated naphthalene are first order and the estimated activation enthalpy Delta H(double dagger) for this process was determined to be Delta H(double dagger) = 116 +/- 8 kJ mol(-1) (Delta S(double dagger) = 37 +/- 25 J K(-1) mol(-1)). Furthermore, density functional theory calculations on the reaction of 1a with hexafluorobenzene, octafluoronaphthalene, octafluorotoluene, 1,2,4-trifluorobenzene, and 1,2,3-trifluorobenzene are presented.


Perioperative Outcomes of Thoracic Outlet Syndrome Surgical Repair in a Nationally Validated Database.
We evaluated the occurrence of thoracic outlet syndrome (TOS) and 30-day postoperative outcomes. Patients undergoing cervical/first rib resection surgery were identified in the American College of Surgeons National Surgical Quality Improvement Program database (2005-2013). Thoracic outlet syndrome types were then examined. Propensity score matching was performed to account for potential confounders; 1180 patients were explored during the study period, 1007 (85.3%) were of the neurogenic TOS (NTOS), 32 (2.7%) patients had arterial TOS (ATOS), and 141 (12.0%) patients had venous TOS (VTOS). Patients with ATOS were significantly older (median age [interquartile range, IQR]-NTOS: 34 [25-44], ATOS: 49.5 [42.5-57], VTOS: 34 [23-43]; P < .001). Median operating time was significantly longer for patients with ATOS. Median in-hospital stay was also longer for patients with ATOS (median length of in-hospital stay [LOS; IQR]-NTOS: 2 [1-4]; ATOS: 6 [3-7]; and VTOS: 5 [2-7] days; P < .001). Patients with VTOS showed twice longer LOS when compared to NTOS after matching. Presentation and treatment of TOS have been studied extensively at highly experienced centers.


LET versus EMLA for pretreating lacerations: a randomized trial.
To compare the anesthetic efficacy of EMLA cream (eutectic mixture of local anesthetics) with that of LET solution (lidocaine, epinephrine, tetracaine) for pretreating lacerations prior to lidocaine injection. This was a randomized, double-blind clinical trial in a convenience sample of 60 patients aged 1 to 59 years with traumatic lacerations. Eligible wounds were uncomplicated, clean lacerations < or = 6 hours old. Finger and toe lacerations were excluded. At the time of initial presentation to triage, patients were randomized to LET or EMLA. A nurse applied the topical anesthetic into the laceration with a 5-mL syringe. A physician assessed the laceration edges for the presence of blanching and adequacy of anesthesia to a 27-gauge needlestick. Supplemental lidocaine was then infiltrated through the wound edges and the pain of infiltration was recorded by the patient (or guardian) on a 100-mm visual analog scale marked "most pain" at the high end. A sample of 44 patients had 90% power to detect a 20-mm difference in injection pain (two-tailed alpha = 0.05). Sixty patients were randomized to LET (29) or EMLA (31). Median age was 8.5 years; 23% were female. Most lacerations were facial and closed with sutures. There was no difference in baseline characteristics between groups. More wounds treated with LET were anesthetic to a needlestick than wounds treated with EMLA (73% vs 40%, p = 0.01); however, there was no between-group difference in the median pain of lidocaine infiltration (LET-12 mm vs EMLA-13 mm, p = 0.89). Pretreatment of simple lacerations with LET or EMLA at the time of patient presentation results in similar amounts of pain of subsequent local infiltration of lidocaine


Non-traumatic gas gangrene presenting as left buttock and thigh pain in a patient with metastatic non-small cell lung cancer.
We report a case of Clostridium septicum myonecrosis in a patient with metastatic non-small cell lung cancer receiving palliative chemotherapy. This is a rare but important differential diagnosis in patients with known malignancy presenting with acute pain. It is critical that the diagnosis is considered and confirmed promptly due to rapid deterioration and a potentially fatal outcome in the absence of aggressive treatment.


Perimalleolar and pedal thromboembolectomy and bypasses to treat distal embolization during aortoiliac aneurysm repairs.
Lower extremity embolization occurs during aortoiliac aneurysm repair and may require major amputation when distal arteries are occluded. Because nonoperative treatments are often ineffective, we evaluated an aggressive operative approach. In the past 11 years, we performed 328 endovascular and 350 open aortoiliac aneurysm repairs. Excluding cases of embolization to iliac, femoral, popliteal, and more proximal tibial vessels, which were treated in a standard fashion, foot ischemia severe enough to produce cadaveric, pregangrenous, or gangrenous skin changes occurred from more distal embolization after seven endovascular and three open aortoiliac aneurysm repairs. Six of these 10 patients underwent thromboembolectomies of both their dorsalis pedis and perimalleolar posterior tibial arteries < or =4 hours of their original operation. In the other four patients, treatment was delayed 7 to 10 days. Because of progressive foot ischemia, arteriography was performed. From these results, four bypasses (3 autologous vein, 1 polytetrafluoroethylene graft) were performed to the transverse metatarsal arch, dorsalis pedis, perimalleolar peroneal artery, or perimalleolar anterior tibial artery. Patency and limb-salvage rates for both thromboembolectomy and bypass procedures were 100% at a mean follow-up of 3.0 years (range, 5 months-8 years). Perimalleolar and foot artery thromboembolectomy and bypasses to arteries as distal as the metatarsal arch can be effective treatment for distal embolization from aortoiliac aneurysm repair. Even when cadaveric, pregangrenous, or gangrenous lesions are present, distal arteriography and operative treatment (thromboembolectomy or bypass) may be indicated to successfully salvage the foot.


Are mean platelet volume and platelet distribution width useful parameters in children with acute rheumatic carditis?
Rheumatic fever (RF) is an inflammatory disease caused by autoimmune response to a preceding group A streptococcal infection. Mean platelet volume (MPV) reflects the platelet size and the rate of platelet production in bone marrow, and it may be used as an indicator of platelet activation and severity of inflammation. Fifty-three consecutive patients diagnosed with acute rheumatic carditis and 53 control subjects were enrolled into this study. Leukocyte and platelet counts were significantly higher in patients with acute carditis before treatment compared with controls, whereas MPV and platelet distribution width (PDW) values were not significantly different between groups. Platelet counts, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) values were decreased significantly in patients with RF after treatment. There was not a significant difference in terms of platelet count between the controls and the patient group after treatment. ESR was found to be correlated with CRP in patients before and after treatment. In conclusion, the results of our study showed that MPV and PDW levels do not change during acute rheumatic carditis before and after treatment.


Extended unambiguous range interferometry.
Phase measuring interferometers generally measure phase modulo 2pi. We present a system which uses fringe contrast to help determine the absolute phase in the interference image within the limits of the coherence length of the illumination. This approach obviates the need for phase unwrapping and is unaffected by surface discontinuities or by data dropout. Since the phase is determined on a point-by-point basis, the processing could be pipelined. The system is set up on a microscope interferometer and produces surface profiles over an array of 512 x 512 points. The measurement range is related to the coherence length of the source and can easily be varied from 0.5 to 2.5 microm. The resolution is limited by the 8-bit quantization of the output.


Developmental changes produced in the retinofugal pathways of rats and ferrets by early monocular enucleations: the effects of age and the differences between normal and albino animals.
Early monocular enucleations were done in rats, either at embryonic day 16 (E16) or on the day of birth, and the surviving uncrossed pathway was studied either at birth for some of the animals enucleated prenatally, or in the adult for all of the other animals. The uncrossed pathways were studied by using HRP as a retrograde tracer. The neonatal enucleations showed the increase of the surviving uncrossed component previously documented by others. In contrast to this, a prenatal enucleation produced a significant reduction in the surviving uncrossed pathway at birth. If these animals survived to be adults, then the surviving uncrossed pathway was slightly increased relative to normal. We conclude that two quite distinct mechanisms have been exposed by these experiments, one acting prenatally and producing a reduction in the uncrossed pathway, and the other acting postnatally and producing an increase. The postnatal effect, which is due to a decrease of the normally occurring ganglion cell death, thus neutralizes the prenatal effect, so that the most effective demonstration of the prenatal effect is to be seen before the period of cell death (early postnatal in rats and ferrets). The same methods were applied to prenatal ferrets at E26-E28 and, in order to see the maximum prenatal effects, the uncrossed pathways were studied at birth in all of these animals. There was a severe reduction of the uncrossed pathway throughout, and this was greatest in the animals with the earliest enucleations. Since the uncrossed pathway in normally reared albino animals is abnormally small, the effects of an early prenatal enucleation in albino rats and ferrets were compared with the effects in normally pigmented animals in order to determine whether the early enucleation was producing an abnormality comparable to the albino abnormality. Prenatal enucleations reduced the uncrossed pathway not only in normally pigmented but also in albino neonatal rats and ferrets. Further, the characteristic position of the nasal border of the temporal retina, which is abnormal in albino animals, was unaffected by the enucleation in either the albino or the pigmented animals, except where, in ferrets, enucleations produced a complete loss of the temporal concentration of ipsilaterally projecting ganglion cells (the temporal crescent). The earlier enucleations showed a greater tendency to produce such a complete loss of the temporal crescent. We conclude that the developmental mechanisms affected by the early enucleations are distinct from those that act to produce the albino abnormality even though both produce an abnormally small uncrossed pathway.(ABSTRACT TRUNCATED AT 400 WORDS)


Executive Dysfunction Related to Binge Drinking in Ischemic Stroke.
Recent evidence has shown that cognitive dysfunction is associated with a history of binge drinking in adolescents who do not have an alcohol use disorder. Most previous studies with adults, however, have failed to show a link between cognitive dysfunction and subdiagnostic binge drinking, nor have any studies investigated the additive cognitive effect of binge drinking to ischemic stroke. To examine whether a pattern of cognitive dysfunction, especially executive and memory dysfunction, in patients with a first-ever ischemic stroke is associated with a history of subdiagnostic binge drinking. We studied 206 first-ever ischemic stroke patients (18-65 years) and 50 healthy, demographically comparable adults-both groups with no alcohol use disorder. After exclusion by matching, 189 patients and 39 healthy participants were included in our study (228 participants). The binge-drinking group included 76 participants; the non-binge-drinking group included 152. A multivariate analysis of covariance was used to compare nine cognitive functions between the two groups, with age, education, and stroke severity used as covariates. Binge drinking had a significant negative effect on executive functions (P<0.001). The non-binge-drinking group outperformed the binge-drinking group on the Stroop Test (P=0.001), Trail Making Test (P=0.002), and a phonemic fluency test (P=0.005). The Binge×Stroke Severity interaction (P=0.037) indicated that a history of binge drinking increased the negative effect of stroke on executive functions. Subdiagnostic binge drinking may exacerbate the adverse effects of ischemic stroke on executive dysfunction.


Effects of alpha- and beta-adrenergic receptor stimulation and oxytocin receptor blockade on milking characteristics in dairy cows before and after removal of the teat sphincter.
Alpha (alpha)- and beta (beta)-adrenergic receptors in the bovine mammary gland are mainly present in the teat muscles and in the region where large milk ducts reach the cisternal cavities. The aim of the study was to test the hypothesis that the region of the large mammary ducts is the most important location of alpha- and beta-adrenergic receptor stimulation affecting milk ejection and milk removal. Effects of alpha- and beta-adrenergic receptor stimulation and of oxytocin (OT) receptor blockade on milking characteristics were tested in six cows. Milk flow was measured before and after the distal part of one teat, including the teat canal and teat sphincter, had been partly amputated. Before the operation, milk yield and peak flow rate decreased during alpha-adrenergic receptor stimulation and during the OT receptor blockade, and increased during beta-adrenergic stimulation. After removal of the teat tip, relations of milk yield and peak flow rates after administration of alpha- and beta-agonists and after application of an OT receptor blocking agent were similar to those before operation. Only total milk yield had decreased in the teat-amputated quarter owing to unhindered flow of cisternal milk before cluster attachment. Since responses to alpha- and beta-adrenergic receptor stimulation as well as to OT receptor blockade do not differ with or without the teat sphincter, it is concluded that milk flow is mainly influenced by the muscle tone of the large mammary ducts.


Zopiclone: sleep and performance studies in healthy man.
Effects of 2.5, 5.0, 7.5, and 10.0 mg zopiclone on sleep and on performance the next day were studied in 6 healthy adult males aged between 21 and 33 years. The experiment was double-blind and placebo controlled. 5.0 and 10.0 mg zopiclone decreased the amount of awake activity and drowsy (stage 1) sleep over the first 6 h of sleep, but this effect was only present for the whole sleep period with the 10.0-mg dose. The duration and percentage of stage 3 sleep were increased with 7.5 mg. The 7.5- and 10.0-mg doses increased the combined duration of stages 2, 3, and 4 sleep over the first 6 h and over the whole night. The first period of rapid eye movement sleep was delayed with 7.5 mg, and with 10.0 mg the time spent in rapid eye movement sleep was reduced during the first 6 h of sleep, but not over the whole night. The number of substitutions in the digit symbol substitution test was decreased 9 h after ingestion of 7.5 and 10.0 mg, and the number of symbols copied reduced after 10.0 mg. The clinical dose range of zopiclone is likely to be up to 7.5 mg. The latter dose provides a useful hypnotic effect with minimal residual effects the next day, whilst 5.0 mg is appropriate for those involved in skilled tasks where even the most minor changes in performance during the early part of the next day must be avoided.


The use of mental health measures in nursing home research.
To examine the quality of mental health research in nursing homes, 130 articles published in six geriatric specialty and health care delivery journals were reviewed. Thirty-nine (30%) articles used a mental health measure. Measures of cognitive function were most common, being used in 32 (25%) of the articles reviewed. Twenty-three (18%) studies measured abnormal mental experiences and 17 (13%) articles measured behavioral disorder. Many articles used measures or determinations with no established reliability. Twenty-six of the articles which used a mental health measure also used a measure of activities of daily living or physical function. Retrospective and prospective studies were similar in number. A minority of articles used control groups, random samples, or prepost measures while a majority (64%) identified an outcome measure. We conclude that nursing home research can be improved by the increased use of reliable measures of cognition and abnormal mental experiences and by the development of reliable measures of behavioral disorder. Study design can be improved by identifying a priori hypotheses and by the increased use of random sampling and control/comparison groups.


Late complications of Silastic duraplasty: low-virulence infections. Case report.
The authors describe three patients with expanding hemorrhagic mass lesions who presented 13 to 18 years after undergoing Silastic duraplasty. In all patients, results of bacteriological cultures of the masses obtained intraoperatively were positive, revealing low-virulence bacteria. Two of the patients were treated with antibiotic drugs and made a good recovery. The third did not receive antibiotic medications initially and later developed an epidural empyema that necessitated reoperation, but subsequently made a complete recovery. Vascularized neomembranes are generally agreed to be causes of the expanding masses, but the possibility that patients could be harboring chronic infections must be considered. Thus, on removal of duraplasty materials a complete bacteriological culture should be obtained, and if it is positive the proper antibiotic therapy should be administered. Furthermore, the creation of a registry of patients who have received implants is advocated to facilitate tracking of implanted material in case of complications.


Modulation-format-independent OSNR monitoring insensitive to cascaded filtering effects by low-cost coherent receptions and RF power measurements.
Optical signal-to-noise ratio (OSNR) monitoring is indispensable for ensuring robust and flexible optical networks that provide failure diagnosis, dynamic lightpath provisioning and modulation format adaptation. We propose and experimentally demonstrate a low-cost, modulation-format-independent OSNR monitoring scheme utilizing reduced-complexity coherent receptions, electrical filtering and radio frequency (RF) power measurements. By measuring the RF power of the coherently received baseband signals at three different frequency components, the proposed OSNR monitor is also insensitive to spectral narrowing induced by cascaded wavelength selective switches (WSSs). We experimentally demonstrate accurate data-format-transparent and filtering-effect-insensitive OSNR monitoring for 25-Gbaud dual-polarization (DP-) transmissions with QPSK, 16-QAM and 64-QAM signals over various distances with different amount of filtering effects by cascaded WSSs. We further characterize the influence of different system parameters, such as the bandwidth of the electrical low-pass filter, the laser frequency offset and laser linewidth on the accuracy of the proposed OSNR monitor. The robustness of the proposed OSNR monitoring scheme to fiber nonlinearities, calibration parameter mismatches and variations of WSS parameters are also investigated.


Sexuality and obesity, a gender perspective: results from French national random probability survey of sexual behaviours.
To analyse the association between body mass index (BMI) and sexual activity, sexual satisfaction, unintended pregnancies, and abortions in obese people and to discuss the implications for public health practices, taking into account the respondents' and their partners' BMI. Random probability survey of sexual behaviours. National population based survey of 12 364 men and women aged 18-69 living in France in 2006. Random selection of 5535 women and 4635 men, of whom 3651 women and 2725 men were normal weight (BMI 18.5-<25), 1010 women and 1488 men were overweight (BMI 25-<30), and 411 women and 350 men were obese (BMI >30). Obese women were less likely than normal weight women to report having a sexual partner in the past 12 months (odds ratio 0.71, 95% confidence interval 0.51 to 0.97). Obese men were less likely than normal weight men to report more than one sexual partner in the same period (0.31, 0.17 to 0.57, P<0.001) and more likely to report erectile dysfunction (2.58, 1.09 to 6.11, P<0.05). Sexual dysfunction was not associated with BMI among women. Obese women aged under 30 were less likely to seek healthcare services for contraception (0.37, 0.18 to 0.76) or to use oral contraceptives (0.34, 0.15 to 0.78). They were also more likely to report an unintended pregnancy (4.26, 2.21 to 8.23). There is a link between BMI and sexual behaviour and adverse sexual health outcomes, with obese women less likely to access contraceptive healthcare services and having more unplanned pregnancies. Prevention of unintended pregnancies among these women is a major reproductive health challenge. Healthcare professionals need to be aware of sensitivities related to weight and gender in the provision of sexual health services.


Immunological follow-up of 41 renal allograft recipients.
A series of immunological parameters were used to follow 41 necrokidney transplantations, in an investigation of the correlation between these parameters and graft function, rejection and graft survival. The results showed that patient and graft survival were not dependent on the occurrence of rejection, but were related to decrease in lumphocyte counts and IgG in the initial post-operative period. Initial decreases in lymphocyte count, IgG, IgA and IgM were found. There was no correlation between initial donor-recipient MLC response and graft survial. In the post-operative period there were falls in PHA, PWM and PPD responses and in numbers of cells forming T and B rosettes, but no change in MLC response. Lowest measured values for lymphocytes and IgC tended to occur just before rejection, but there was no depression of the measured in vitro immune responses at this time. However, MLC and PHA responses were depressed during rejection. When these results are compared with similar results in the literature, which shows a lack of convincing correlation between existing immunological tests and the course of transplantation, it is concluded that the immunological tests available today are unsatisfactory for use in monitoring immune response as an aid to the adquate immunosuppression of receipients.


Monitoring and evaluation of breast cancer screening programmes: selecting candidate performance indicators.
In the scope of the European Commission Initiative on Breast Cancer (ECIBC) the Monitoring and Evaluation (M&E) subgroup was tasked to identify breast cancer screening programme (BCSP) performance indicators, including their acceptable and desirable levels, which are associated with breast cancer (BC) mortality. This paper documents the methodology used for the indicator selection. The indicators were identified through a multi-stage process. First, a scoping review was conducted to identify existing performance indicators. Second, building on existing frameworks for making well-informed health care choices, a specific conceptual framework was developed to guide the indicator selection. Third, two group exercises including a rating and ranking survey were conducted for indicator selection using pre-determined criteria, such as: relevance, measurability, accurateness, ethics and understandability. The selected indicators were mapped onto a BC screening pathway developed by the M&E subgroup to illustrate the steps of BC screening common to all EU countries. A total of 96 indicators were identified from an initial list of 1325 indicators. After removing redundant and irrelevant indicators and adding those missing, 39 candidate indicators underwent the rating and ranking exercise. Based on the results, the M&E subgroup selected 13 indicators: screening coverage, participation rate, recall rate, breast cancer detection rate, invasive breast cancer detection rate, cancers > 20 mm, cancers ≤10 mm, lymph node status, interval cancer rate, episode sensitivity, time interval between screening and first treatment, benign open surgical biopsy rate, and mastectomy rate. This systematic approach led to the identification of 13 BCSP candidate performance indicators to be further evaluated for their association with BC mortality.


Dual roles for c-Jun N-terminal kinase in developmental and stress responses in cerebellar granule neurons.
c-Jun N-terminal kinases (JNKs) typically respond strongly to stress, are implicated in brain development, and are believed to mediate neuronal apoptosis. Surprisingly, however, JNK does not respond characteristically to stress in cultured cerebellar granule (CBG) neurons, a widely exploited CNS model for studies of death and development, despite the regulation of its substrate c-Jun. To understand this anomaly, we characterized JNK regulation in CBG neurons. We find that the specific activity of CBG JNK is elevated considerably above that from neuron-like cell lines (SH-SY5Y, PC12); however, similar elevated activities are found in brain extracts. This activity does not result from cellular stress because the stress-activated protein kinase p38 is not activated. We identify a minor stress-sensitive pool of JNK that translocates with mitogen-activated protein kinase kinase-4 (MKK4) into the nucleus. However, the major pool of total activity is cytoplasmic, residing largely in the neurites, suggesting a non-nuclear role for JNK in neurons. A third JNK pool is colocalized with MKK7 in the nucleus, and specific activities of both increase during neuritogenesis, nuclear JNK activity increasing 10-fold, whereas c-Jun expression and activity decrease. A role for JNK during differentiation is supported by modulation of neuritic architecture after expression of dominant inhibitory regulators of the JNK pathway. Channeling of JNK signaling away from c-Jun during differentiation is consistent with the presence in the nucleus of the JNK/MKK7 scaffold protein JNK-interacting protein, which inhibits JNK-c-Jun interaction. We propose a model in which distinct pools of JNK serve different functions, providing a basis for understanding multifunctional JNK signaling in differentiating neurons.


Congenital asplenia and anomalies of the gastrointestinal tract.
Congenital asplenia has been traditionally described in association with cardiopulmonary anomalies (Ivemark syndrome). A case of congenital asplenia with duplication of the hindgut and genitourinary tract, myelomeningocele, situs inversus abdominis, and imperforate anus generated interest in review of the gastrointestinal anomalies of 36 patients who died of the disease in Childrens Hospital of Los Angeles. A significant number were found to have situs inversus, malrotation of the bowel, esophageal varices, duplication and hypoplasia of the stomach, Hirschsprung's disease, imperforate anus, and duplication of the hindgut. These patients present with symptoms referable to their gastrointestinal anomalies and may not draw attention to the concomitant cardiopulmonary anomalies or to the absence of the spleen. It becomes important, therefore, to establish the presence of the spleen in infants suffering from various anomalies of the gastrointestinal tract because of the overwhelming septicemia that is known to complicate the clinical management of these patients.


Non-Medical Use of Novel Synthetic Opioids: A New Challenge to Public Health.
Background: In the last decade there has been a progressive increase in the use of new psychoactive substances (NPSs) that are not yet under international control. In particular, novel synthetic opioids (NSOs) have reappeared on the recreational drug market in the last few years. As a result, the use of NSOs has increased rapidly. This poses an emerging and demanding challenge to public health. Aim: To raise awareness among clinicians and other professionals about NPSs, especially NSOs, to summarize current knowledge about pharmacological properties, forms of NSO on the market, pattern of use, effects and consequences of use. Methods: An electronic search was carried out on the Medline/PubMed and Google Scholar databases to find selected search terms. Results: Some NPSs are already controlled, while others can be legally sold directly on the drug market (mainly via internet, less so by drug dealers) or be used as precursors for the synthesis of other designer drugs that mimic the psychoactive effects of controlled substances. Potential side-effects of NSOs include miosis, sedation, respiratory depression, hypothermia, inhibition of gastrointestinal propulsion, death (from opioid overdose). Conclusions: The severity of the opioid crisis has intensified with the introduction of highly potent NSOs on the drug market. As long as addicts are dying from overdose or similar causes, there is something more constructive to do than waiting for addicts to overdose on heroin at a place located near a remedy, as if to say, within reach of naloxone.


Dissociative photodetachment vs. photodissociation of aromatic carboxylates: the benzoate and naphthoate anions.
The competition between dissociative photodetachment and photodissociation of cold benzoate and naphthoate anions was studied through measurement of the kinetic energy of the neutral fragments and intact parent benzoyloxy and naphtoyloxy radicals as well as by detecting the anionic fragments whenever they are produced. For the benzoate anion, there is no ionic photodissociation and the radical dissociation occurs near the vertical photodetachment energy. This is in agreement with DFT calculations showing that the dissociation energy in CO2 and C6H5˙ is very low. The dissociation barrier can be deduced from experimental results and calculations to be (0.7 ± 0.1) eV, which makes the benzoyloxyradical C6H5COO˙ very unstable, although more stable than the acetyloxy radical. In the case of naphthoate, the observation of negative fragments at low excitation energies demonstrates the opening of the ionic photodissociation channel in the excited state of the naphthoate anion, whose yield decreases at higher energies when the dissociative photodetachment channel opens.


Sexually transmitted infections and associated socio-demographic and behavioural factors in women seeking primary care suggest Madagascar's vulnerability to rapid HIV spread.
To examine sexually transmitted infections (STIs) and associated socio-demographic and behavioural factors in women seeking care for genital discharge syndrome in Antananarivo, Madagascar. One thousand and sixty-six consecutive symptomatic women were interviewed and examined; bacterial vaginosis (BV), vulvovaginal candidiasis, trichomoniasis (TV), cervical infection (CI) due to chlamydial or gonococcal infections, and syphilis seroreactivity were determined by laboratory diagnosis. Associations between STIs and individual characteristics were evaluated using bivariate and logistic regression analyses. The prevalence of BV, TV, CI, and syphilis seroreactivity was, respectively, 85%, 16%, 49%, 16% in 94 prostitutes; 70%, 18%, 30%, 13% in 96 occasional sex traders; and 53%, 24%, 17%, and 4% in 876 general women. CI was independently and positively associated with a symptomatic partner, new sex partner in last 3 months, unfaithful partner, prostitution, joblessness and being < 25 years old. Syphilis was associated with low schooling, young age at coital debut, sex trading, and > 1 sex partner in the previous 3 months. These high STI rates and associated characteristics suggest the local vulnerability to rapid HIV spread and show the need for prevention efforts that involve youth, prostitutes, occasional sex traders, sex clients, and men who have concurrent sexual partnerships.


Recurrent Fever and Failure to Thrive in an 11-Year-Old Boy.
Recurrent fever is frequent among children and mostly associated with viral infections inoculated via social contacts with others of the same age. Rarely, severe conditions such as hematological malignancies, pediatric rheumatoid diseases, chronic infections, or inherited recurrent fever syndromes are causative. Herein, we present the case of an 11-year-old boy with frequently recurring high-fever episodes since early childhood, failure to thrive, and iron deficiency who was found to have classical celiac disease (CD) with highly elevated tissue transglutaminase and anti-gliadin antibodies and marked duodenal villous atrophy. Upon implementation of a gluten-free diet, the boy ceased to have fevers, antibodies decreased markedly, his iron status improved, and he significantly gained weight. Although infrequent, recurrent fever should be included into the polymorphic clinical picture of CD, and the threshold of testing for diagnostic antibodies should be low in such patients.


Influence of SNPs in nutrient-sensitive candidate genes and gene-diet interactions on blood lipids: the DiOGenes study.
Blood lipid response to a given dietary intervention could be determined by the effect of diet, gene variants or gene-diet interactions. The objective of the present study was to investigate whether variants in presumed nutrient-sensitive genes involved in lipid metabolism modified lipid profile after weight loss and in response to a given diet, among overweight European adults participating in the Diet Obesity and Genes study. By multiple linear regressions, 240 SNPs in twenty-four candidate genes were investigated for SNP main and SNP-diet interaction effects on total cholesterol, LDL-cholesterol, HDL-cholesterol and TAG after an 8-week low-energy diet (only main effect) ,and a 6-month ad libitum weight maintenance diet, with different contents of dietary protein or glycaemic index. After adjusting for multiple testing, a SNP-dietary protein interaction effect on TAG was identified for lipin 1 (LPIN1) rs4315495, with a decrease in TAG of 20.26 mmol/l per A-allele/protein unit (95% CI 20.38, 20.14, P=0.000043). In conclusion, we investigated SNP-diet interactions for blood lipid profiles for 240 SNPs in twenty-four candidate genes, selected for their involvement in lipid metabolism pathways, and identified one significant interaction between LPIN1 rs4315495 and dietary protein for TAG concentration.


An experimental test of Darwin's naturalization hypothesis.
One of the oldest ideas in invasion biology, known as Darwin's naturalization hypothesis, suggests that introduced species are more successful in communities in which their close relatives are absent. We conducted the first experimental test of this hypothesis in laboratory bacterial communities varying in phylogenetic relatedness between resident and invading species with and without a protist bacterivore. As predicted, invasion success increased with phylogenetic distance between the invading and the resident bacterial species in both the presence and the absence of protistan bacterivory. The frequency of successful invader establishment was best explained by average phylogenetic distance between the invader and all resident species, possibly indicating limitation by the availability of the unexploited niche (i.e., organic substances in the medium capable of supporting the invader growth); invader abundance was best explained by phylogenetic distance between the invader and its nearest resident relative, possibly indicating limitation by the availability of the unexploited optimal niche (i.e., the subset of organic substances supporting the best invader growth). These results were largely driven by one resident bacterium (a subspecies of Serratia marcescens) posting the strongest resistance to the alien bacterium (another subspecies of S. marcescens). Overall, our findings support phylogenetic relatedness as a useful predictor of species invasion success.


Attempts to increase the holographic exposure index of photographic materials.
The holographic exposure index (HEI) relates the radiant energy necessary for recording a hologram to the diffraction efficiency to be achieved. In addition to the sensitometric speed of the recording material, the HEI takes into account that the modulation transfer function and macroscopic transfer characteristics, depolarization, and losses in the object beam path determine the share of the laser flux to be split off for the object beam. Several techniques expected to save exposure are examined. Extended development may increase the HEI by a factor of about 2, but light scattering due to granularity increases more. Combining a hologram exposure with incoherent preexposure or postexposure is governed by quite different characteristics, depending upon which of the exposures is variable or whether both are proportional. The characteristics alpha(E),beta(E) for amplitude holograms and gamma(E),delta (E) for bleached holograms are used for the analysis and verified experimentally. Preexposure or postexposure is of use only if extreme underexposure is unavoidable. When superimposing several holograms a decrease in diffraction efficiency in the order of exposure was found. Finally, Scientia 8E70 and 10E70 plates and 10E70 film were hypersensitized by bathing. Distilled water and a relatively diluted ammonia bath yield the best results by increasing both the sensitometric speed and the values of the macroscopic transfer characteristics, the gain in HEI becoming up to 3 for the slowest plate.


Biomimetic mineralisation of phosphorylated dentine by CPP-ACP.
Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) has the potential to induce the biomimetic mineralisation of dentine collagen fibrils. This study aimed to demonstrate in vitro the ability of CPP-ACP to form apatite crystals on phosphorylated dentine collagen fibrils. Dentine slices with a 2-mm thickness were prepared from sound human third molars. The slices were etched with phosphoric acid to expose the collagen fibres. Sodium trimetaphosphate was then used to phosphorylate the exposed collagen fibres. CPP-ACP paste was topically applied to the surface of the phosphorylated slices, which were then immersed in a metastable calcium phosphate remineralising solution and incubated at 37°C for 10 days. The CPP-ACP paste and the remineralising solution were replaced every two days. Phosphorylated dentine slices without a CPP-ACP application and non-phosphorylated dentine slices with a CPP-ACP application were prepared and used for comparison. The slices were examined using scanning electron microscope (SEM), diffuse reflectance-Fourier transform infrared spectroscopy (DR-FTIR) and X-ray diffraction (XRD). The SEM results revealed the presence of intrafibrillar and interfibrillar crystal nucleation and growth along the phosphorylated dentine collagen fibres. The DR-FTIR and XRD confirmed that the crystals were hydroxyapatite. No apatite crystal nucleation and growth were observed in either the slices that had no non-phosphorylation or those without CPP-ACP application. CPP-ACP can induce the biomimetic mineralisation of dentine through apatite formation along and between the phosphorylated dentine collagen fibres. The in vitro study imitated the application of CPP-ACP to exposed dentine tooth surfaces in the mouth. This could lead to the development of a new therapeutic technique for the treatment of tooth hypersensitivity.


Genetics of obesity.
Obesity is a complex phenomenon that involves interactions between environmental and genetics factors. The genetic studies in animal models and humans has allowed great progress in the knowledge of body weight regulation. Identifying the hypothalamic leptin/melanocortin pathway as critical in many cases of monogenic obesity has permitted targeted, hypothesis-driven experiments to be performed, and has implicated new candidates as causative for previously uncharacterized clinical cases of obesity. Narrative review. PubMed, Lilacs and ScieLo databases were searched with the terms "obesity", "genetics" and limited only for" all child 0-18 years". Numerous studies in children and adolescents, have tried to identify candidate genes. At present, the results are not conclusive. Thus, is yet premature genotype obese child on a large scale for predictive testing. Meanwhile, the effects of mutations in the melanocortin-4 receptor gene, for which the obese phenotype varies in the degree of severity among individuals, are now thought to be influenced by one's environmental surroundings. Molecular approaches have revealed that syndromes previously assumed to be controlled by a single gene are conversely regulated by multiple elements. When specific treatments based on recent discoveries become available, genetic testing could help to discriminate different types of obesity that may respond differentially to therapeutic measures.


A cost-benefit analysis of pre- and post-lambing anthelmintic treatments to twin-bearing ewes on commercial farms in the southern North Island of New Zealand.
To conduct a cost-benefit analysis of the administration of anthelmintics to adult ewes around lambing. Production data from comparisons of different anthelmintic treatments with no treatment were used in a cost-benefit analysis. The data were from 14 trials (part of an experiment carried out on one farm in 1 year) conducted on sheep and beef farms (eight in 2011 and six in 2012) in the Wairarapa region of New Zealand. The cost structure involved the purchase price of products and the labour cost of administration. The four key benefits identified for the calculation of economic returns, relative to untreated ewes, were: increased value of ewes sold (culled) at weaning, additional lambs weaned related to ewe liveweight at mating, increased total weight of lamb weaned per ewe, and reduced number of ewes requiring removal of soiled wool at weaning due to a lower dag score. Commercial values for these variables as at December 2013 were used, with the measured production data, to calculate a net (NZ$) benefit for every treatment-trial combination. The economic return on treating ewes around lambing with anthelmintics was highly variable and across all trials treatment resulted in a financial loss in 18/38 (47%) groups of ewes. The mean net benefit from pre-lambing administration of a controlled release capsule (CRC) containing albendazole and abamectin was 5.36 (95% CI=-2.64 to 13.35) $/ewe, but overall was not different from zero (p=0.171). A breakdown of the overall gross benefit into its various components showed that weight of lamb weaned per ewe had the largest influence (a mean benefit of $5.68/ewe), followed by ewe liveweight pre-mating ($2.45/ewe), ewe liveweight at weaning ($0.66/ewe) and reduced dag score ($0.15/ewe). Other anthelmintic treatments all showed highly variable responses amongst trials, with some negative cost-benefits. There was no significant difference between any of the treatments except a short-acting oral treatment at tail-docking had a lower net benefit than a CRC containing albendazole administered pre-lambing (p<0.05). A positive financial return resulting from the anthelmintic treatment of adult ewes around lambing is neither consistent nor predictable, and is often not achieved. Given that the additional costs of accelerating the development of anthelmintic resistance were not included in these calculations, farmers need to consider carefully the merits of administering anthelmintics to ewes around lambing.