A cellular analysis of meristem activity at the end of flowering points to cytokinin as a major regulator of proliferative arrest in Arabidopsis.
In monocarpic plants, all reproductive meristem activity arrests and flower production ceases after the production of a certain number of fruits. This proliferative arrest (PA) is an evolutionary adaptation that ensures nutrient availability for seed production. Moreover, PA is a process of agronomic interest because it affects the duration of the flowering period and therefore fruit production. While our knowledge of the inputs and genetic factors controlling the initiation of the flowering period is extensive, little is known about the regulatory pathways and cellular events that participate in the end of flowering and trigger PA. Here, we characterize with high spatiotemporal resolution the cellular and molecular changes related to cell proliferation and meristem activity in the shoot apical meristem throughout the flowering period and PA. Our results suggest that cytokinin (CK) signaling repression precedes PA and that this hormone is sufficient to prevent and revert the process. We have also observed that repression of known CK downstream factors, such as type B cyclins and WUSCHEL (WUS), correlates with PA. These molecular changes are accompanied by changes in cell size and number likely caused by the cessation of cell division and WUS activity during PA. Parallel assays in fruitfull (ful) mutants, which do not undergo PA, have revealed that FUL may promote PA via repression of these CK-dependent pathways. Moreover, our data allow to define two phases, based on the relative contribution of FUL, that lead to PA: an early reduction of CK-related events and a late blocking of these events.


Comparative metagenomics and characterization of antimicrobial resistance genes in pasteurized and homemade fermented Arabian laban.
The aim of this study was to investigate bacterial diversity and function in a fermented milk drink called laban, which is traditionally served in the Middle East, Africa, and Indian subcontinent. Pasteurized laban (LBP) and unpasteurized, homemade, raw laban (LBR) underwent 16S rRNA gene amplicon and shotgun sequencing to analyze their bacterial community, presence of antimicrobial resistance genes (ARGs), and metabolic pathways. This study highlighted relatively greater diversity in LBR bacterial populations compared to LBP, despite containing similar major taxa that consisted primarily of Firmicutes followed by Proteobacteria, Bacteroidetes, and Actinobacteria. The dominant species, Streptococcus thermophilus, was relatively more abundant in LBP (80.7%) compared to LBR (47.9%). LBR had increased diversity and higher relative abundance of several known probiotic bacteria, such as Streptococcus salivarius and Lactococcus lactis, whereas Lactobacillus acidophilus was detected at a higher abundance in LBP. Pathogens like Acinetobacter baumannii, Streptococcus pneumoniae, Streptococcus pyogenes, and Escherichia coli had lower abundance in LBP compared to LBR. Thirty-three ARGs were detected in LBR compared to nine in LBP and are responsible for resistance to 11 classes of antibiotics. A significant proportion of the metagenomes from both types of laban were assigned to housekeeping functions, such as amino acid metabolism, translation, membrane transport, and carbohydrate metabolism. LBR demonstrated increased diversity in probiotics and metabolic functions compared to LBP. However, the relatively high diversity of pathogenic and opportunistic bacteria and ARGs in LBR raises safety concerns and highlights the need for a more hygienic environment for the processing of homemade fermented dairy foods.


Prevalence and molecular characterization of Cryptosporidium species in cattle and buffalo calves in Mumbai region of India.
Faecal samples of cattle and buffaloes of Mumbai region collected between November 2012 to June 2013 were analysed by conventional and molecular tools to note the prevalence of cryptosporidiosis and species involved in the infection. Conventional analysis viz., direct faecal smear examination, faecal smear examination after normal saline sedimentation, Sheather's floatation and Sheather's floatation sedimentation smear methods demonstrated oocysts of Cryptosporidium in 141 (36.06 %) of 391 samples with higher occurrence in buffaloes (36.99 %) than cattle (34.48 %). Diarrhoeic loose faeces showed higher prevalence (42.07 %) than apparently normal faeces (31.72 %) irrespective of the host species. When data were arranged as per age groups viz., calves of 0-1 month, 1-2 months, 2-3 months and adults, the highest prevalence was noted in the youngest group (47.12 %) declining gradually with the advancing age with lowest (6.25 %) in adults indicating inverse correlation between prevalence rate and age of the host. These differences were statistically significant in case of buffaloes. Cryptosporidium andersoni was tentatively identified by morphometric analysis. By employing molecular tools like nested PCR, PCR-RFLP and sequence analysis of few samples showed good correlation in the identification of species of Cryptosporidium involved in the infection and demonstrated occurrence of C. parvum, C. ryanae and C. bovis. Thus all the four commonly occurring bovine species of Cryptosporidium were encountered in the study area which appears to be a first record reporting the occurrence of Cryptosporidium with species level identification in large ruminants from Western region of India. Additionally, the public health significance of C. parvum was also discussed in light of epidemiological factors pertaining to the region.


A hierarchy of regulatory genes controls a larva-to-adult developmental switch in C. elegans.
The heterochronic genes lin-4, lin-14, lin-28, and lin-29 control the timing of specific postembryonic developmental events in C. elegans. The experiments described here examine how these four genes interact to control a particular stage-specific event of the lateral hypodermal cell lineages. This event, termed the "larva-to-adult switch" (L/A switch), involves several coordinate changes in the behavior of hypodermal cells at the fourth molt: cessation of cell division, formation of adult (instead of larval) cuticle, cell fusion, and cessation of the molting cycle. The phenotypes of multiply mutant strains suggest a model wherein the L/A switch is controlled by the stage-specific activity of a regulatory hierarchy: At early stages of wild-type development, lin-14 and lin-28 inhibit lin-29 and thus prevent switching. Later, lin-4 inhibits lin-14 and lin-28, allowing activation of lin-29, which in turn triggers the switch in the L4 stage. lin-29 may activate the L/A switch by regulating genes that control cell division, differentiation, and stage-specific gene expression in hypodermal cells.


Yeast sphingolipids.
Many advances in our understanding of fungal sphingolipids have been made in recent years. This review focuses on the types of sphingolipids that have been found in fungi and upon the genes in Saccharomyces cerevisiae, the common baker's yeast, that are necessary for sphingolipid metabolism. While only a small number of fungi have been examined, most contain sphingolipids composed of ceramide derivatized at carbon-1 with inositol phosphate. Further additions include mannose and then other carbohydrates. The second major class of fungal sphingolipids is the glycosylceramides, having either glucose or galactose attached to ceramide rather than inositol phosphate. The glycosylceramides sometimes contain additional carbohydrates. Knowledge of the genome sequence has expedited identification of S. cerevisiae genes necessary for sphingolipid metabolism. At least one gene is known for most steps in S. cerevisiae sphingolipid metabolism, but more are likely to be identified so that the 13 known genes are likely to grow in number. The AUR1 gene is necessary for addition of inositol phosphate to ceramide and has been identified as a target of several potent antifungal compounds. This essential step in yeast sphingolipid synthesis, which is not found in humans, appears to be an excellent target for the development of more effective antifungal compounds, both for human and for agricultural use.


Black corn (Zea mays L.) flour has the potential to improve the gut microbiota composition and goblet cell proliferation in mice fed a high-fat diet.
High-fat diets are associated with intestinal dysbiosis and leaky gut leading to intestinal inflammation. Bioactive components, including phenolic compounds, isolated or in their original food matrix, have alleviated intestinal impairments promoted by a high-fat diet. Black corn (Zea mays L.) is a colored corn in which anthocyanins are the most abundant bioactive compound. Thus, we hypothesized that black corn flour may have preventive effects on poor intestinal health in mice fed a high-fat diet. To study this, 30 C57BL/6 mice were randomly divided into 3 experimental groups receiving the following diets for 8 weeks: normal control (fed a normal diet); high-fat (fed a high-fat diet: 60% of calories from fat); high-fat corn (fed a high-fat diet added with 20% of black corn whole flour). The cecal microbiota analyzed by 16S ribosomal RNA sequencing showed that black corn flour intake increased the relative abundance of Ruminococcus, Roseburia, and Prevotellaceae_UCG-001, and decreased Bacteroides and Faecalibaculum. No difference was observed in the cecal short-chain fatty acids and fecal pH among the experimental groups (P > .05). Further, the consumption of black corn flour improved cecal morphology by increasing the number of goblet cells but with no difference in the crypt depth and width. These findings suggest that black corn flour as a source of anthocyanins could have preventive effects on gut dysbiosis resulting from a high-fat diet. SCFA, short chain fatty acids.


Abnormalities of cingulate cortex in antipsychotic-naïve chronic schizophrenia.
While several morphometric studies have postulated a critical contribution of the cingulate cortex (CC) to the pathophysiology of schizophrenia based on abnormalities in CC volume, other studies have been inconclusive. Most such studies have focused only on changes in cortical volume, whereas other morphometric parameters such as surface area and cortical thickness could be more relevant and possibly account for these discrepancies. Furthermore, factors such as antipsychotic drug use and treatment duration may also influence cortical morphology. To clarify the association between schizophrenia and CC deficits, we investigated morphometric abnormalities of the CC in antipsychotic drug (AD)-naïve chronic schizophrenia patients by comparing T1-weighted magnetic resonance images (T1WI-MRI) from patients (n=17) to healthy controls (n=17) using the surface-based morphometry program FreeSurfer. Partial correlations were examined between abnormal morphometric measures and both clinical variables and cognitive performance scores. Compared to healthy controls, drug-naïve schizophrenia patients exhibited significantly lower volumes in both left rostral anterior CC (rACC) and left posterior CC (PCC). These reductions in CC volume resulted from reduced surface area rather than reduced cortical thickness. There was also a significant relationship between left PCC volume and working memory in patients. No significant correlations were observed between CC volume and clinical variables. The results suggest that abnormalities in the CC as manifested by reduced surface area may contribute to cognitive dysfunction in schizophrenia. This article is part of a Special Issue entitled SI: PSC and the brain.


Efficacy, tolerability and safety of a new medical device, Monurelle Biogel(®) vaginal gel, in the treatment of vaginal dryness: a randomized clinical trial in women of reproductive age.
To prove the efficacy, tolerability and safety of Monurelle Biogel(®) (ZP-025) vaginal gel, which contains a purified, dialyzed, lyophilized bovine colostrum, in women of reproductive age suffering from vaginal dryness. Randomized clinical trial (RCT) (Z7213M01). Five University Gynaecological Units. Ninety-five subjects were allocated at random to receive either ZP-025 (n=48) for about 23 intermenstrual days (1 or 2 times/daily intra-vaginally) or no treatment (lubricants on demand were allowed). Change of Verbal Rating Scale (VRS) total and single score for vaginal symptoms, Vaginal Health Index (VHI) score, Female Sexual Function index (FSFI) and Female Sexual Distress Scale-revised (FSDS-R) scores. A total number of 85 subjects was evaluable for primary analyses. Symptoms (VRS) of vaginal discomfort improved significantly already after 11 days, as compared to the control arm (p<0.0001). The mean VHI score was also significantly higher in ZP-025 group (p<0.001) at the end of the study. The analysis of covariance with the baseline value as covariate carried out on the FSFI Total Score showed a statistically significant difference in favour of the ZP-025 arm (p<0.032). A shift from presence to absence of sexual distress (≤11 points) was more prominent in the ZP-025 arm [10 subjects (40%) in the ZP-025 arm (p<0.0001) and 6 subjects (21.4%) in the control arm (p=0.01)]. Women reported a compliance rate of 100% for one ZP-025 application/day. Local tolerability of ZP-025 was excellent or good in 82.9% of the subjects. The present multicentre RCT supports the use of Monurelle Biogel(®) in women of reproductive age reporting symptoms of vaginal dryness. A positive impact on vaginal health and sexual function was also evident.


Glioblastoma: clinical characteristics, prognostic factors and survival in 492 patients.
Glioblastoma is the most common and most malignant primary brain tumor in adults. The only overall accepted independent prognostic factors are patient age and performance. We present a large single institution patient series examined for prognostic factors using uni- and multivariate survival analysis. 492 patients were included who underwent craniotomy for newly diagnosed glioblastoma WHO grade IV between 1990 and 2007 at our department. The association to patient survival was estimated using log-rank test for univariate analysis and cox regression method for multivariate analysis. Median patient age was 62 years (mean: 60.4 years, range: 22-93 years), the male: female ratio was 1.26:1. Primary genesis was found in 91.0% of cases. A multifocal tumor was present in 110 cases (22.4%). The median pre- and post-operative Karnofsky Performance Score was 70. Total tumor resection was performed in 288 cases (58.5%), subtotal removal in 134 cases (27.2%). The following parameters were significantly associated with survival in univariate analysis: age, performance, primary genesis, multifocal tumor, neurological deficit, neuropsychological findings, seizures, incidental finding, total or subtotal resection, radiotherapy, chemotherapy, combined radio-/chemotherapy with temozolomide, re-craniotomy, second tumor in patient history. The following parameters were significantly associated with survival in multivariate analysis: age, performance, multifocal tumor, total or subtotal resection, radiotherapy, chemotherapy, combined radio-/chemotherapy with temozolomide. In addition to patient age and performance, we identified multiple lesions and resection status as independent prognostic factors. Radiotherapy, chemotherapy and combined radio-/chemotherapy with temozolomide were significantly associated with prolonged survival.


Cancer research activity in the Arab world: a 15-year bibliometric analysis.
The Arab region comprises 22 countries located in the Middle East and North Africa, sharing cultural and linguistic ties. Arab countries have continued to lag in terms of biomedical research compared to other nations for several past decades. Cancer is a major public health concern, being the second leading cause of death globally. Given that high research activity on cancer reflects positively on screening programs, awareness, and clinical practice, this article aimed to examine the activity and trend of cancer research in the Arab world between 2005 and 2019. Between 2005 and 2019, the number of cancer-related articles published by each Arab country, and regarding 27 different types, was assessed using the PubMed database. Numbers were normalized with respect to each country's average population and average Gross Domestic Product (GDP). Arab countries contributed to 1.52% of total cancer publications. The number of cancer publications has steadily grown since 2005, with the last 7 years alone witnessing 75.69% of the total Arab cancer-related publications. In terms of publications per million persons, Qatar ranked first (393.74 per million persons), while in terms of publications per national GDP, Egypt ranked first (464.27 per billion US dollars). Breast, liver, and colorectal cancers had the highest numbers of all Arab cancer-related publications, while testicular, vulvar, and gallbladder cancers had the least. This paper pools information and insight for scientists, clinicians, funders, and decision-makers on the actualities and developments of cancer research in the Arab world. Addressing the barriers facing cancer research remains a cornerstone in the plan to improve the Arab world's output and contribution to the field of oncology.


Value of routine preoperative chest x-rays: a meta-analysis.
The purpose of this study was to estimate the frequency with which routine postoperative chest x-rays lead to clinically relevant new information. All articles in English, French and Spanish relating to routine chest radiography in North American or European populations were reviewed, using the Medline database and references listed in reviews and periodicals published from 1966 to 1992, inclusive. Twenty-one reports which supplied sufficient information were included for meta-analysis. On average, abnormalities were found in 10% of routine preoperative chest films. In only 1.3% of films were the abnormalities unexpected, i.e., were not already known or would not otherwise have been detected (95% CI: 0 to 2.8%). These findings were of sufficient importance to cause modification of management in only 0.1% (95% CI: 0 to 0.6%). The frequency with which the new information influenced health could not be estimated. Assuming only the direct cost to the health care system of each radiograph ($23), each finding which influenced management in any way would cost $23,000. It is concluded that in North American or European populations when a reliable history and a clinical examination are carried out, the cost of this test is so high relation to the clinical information provided that it is no longer justifiable.


The phenomenon of drop in output at larger field sizes for telecobalt units.
It is known that the output factors (OPFs) for external-beam radiotherapy units increase with field size due to increased scattered radiation from the collimator system. Saturation in the OPF value is generally reported beyond approximately 30 × 30 cm(2). For the first time, to the best of our knowledge, we report on a drop in OPF values, although marginal, measured for a telecobalt machine beyond the 38 × 38 cm(2) field size. We believe that reporting and explaining the results will lead to a better understanding of the scatter composition of the radiation from telecobalt machines. This also has the potential to impact the estimation of low dose regions in patients, in addition to being a purely scientific inquiry. We used Monte Carlo (MC) simulations to validate the measured values. The MC data showed that the decrease in OPF was due to decreased scatter from the machine head.


National distribution of chemical concentrations in mussels and oysters in the USA.
Since 1986 the NOAA National Status and Trends (NS&T) Program Mussel Watch has monitored concentrations of trace chemicals in the coastal United States by sampling mussels, oysters, and sediment. The sediment data have been used to define the status or geographic distribution of chemical concentrations (Daskalakis, K. D., & O'Connor, T. P. (1995). Distribution of chemical contamination in coastal and estuarine sediments. Marine Environmental Research 40, 381-398) and the molluscan data have provided an estimate of temporal trends (O'Connor, T. P. (1996). Trends in chemical concentrations in mussels and oysters collected along the US coast from 1986 to 1993. Marine Environmental Research 41,183-200, O'Connor, T. P. (1998). Mussel Watch results from 1986 to 1996. Marine Pollution Bulletin 37, 14-19). This paper centers on chemical concentrations in mollusks at 263 sites around the United States. It provides perspective on concentration ranges and on geographic distributions. For most organic chemicals and lead, concentrations vary in proportion to numbers of people living near a site. For elements, other than lead, high concentrations in mollusks can be due more to natural factors than to human activity. Concentrations of PAHs in tissues of mussels from urban areas are in a range reported to exert biological responses.


Wound healing in endoscopic sinus surgery: Phase 1 clinical trial evaluating the role of Chitogel with adjuvants.
This study aimed to determine the safety and efficacy of Chitogel, with and without Deferiprone (Def) and Gallium Protoporphyrin (GaPP), as a promoter of wound healing to improve surgical outcomes after endoscopic sinus susgery. A double-blinded, randomised control human clinical trial was conducted in patients undergoing ESS as a treatment for chronic rhinosinusitis. Participants underwent functional ESS or FESS with drill out as required and were randomised to receive test product Chitogel, Chitogel in combination with Def or Def-GaPP versus no packing (control). Ostial stenosis and persistent inflammation are the main reasons for revision endoscopic sinus surgery (ESS). Post-operative (PO) dressings can improve PO wound healing and patient outcomes after ESS. Eighty two patients were included in this study with 79 patients completing the study with 40 undergoing full house FESS and 39 FESS plus frontal drillout. Patients were followed up at 2, 6 and 12 weeks PO, and outcome scores such as SNOT-22, VAS and LKS, pre and post-surgery (12 weeks) were compared. Seventy nine patients completed the study, there was a significant reduction in SNOT-22 score and improvement of VAS at 12 weeks in patients treated with Chitogel compared to control (p < .05). In those patients, the mean ostium area for the Chitogel and the Chitogel + Def + GaPP groups was higher across all three sinuses compared to the no-treatment control group, without statistical significance. Sphenoid sinus ostium was significantly more patent in patients treated with Chitogel compared to the control at the 12-week time point (p < .05). Chitogel as a PO dressing after ESS results in the best patient-reported symptom scores and objective measurements. The combination of Def and GaPP to Chitogel though proving safe, had no effect on the ostium patency or mucosal healing.


Childhood myelodysplastic syndromes with 11p15 translocation.
Two cases of childhood myelodysplastic syndrome with chromosome abnormalities involving band 11p15 are described. The first case, with inv(11)(p15q23), had a complex clinical course; the initial diagnosis was aplastic anemia, then refractory anemia with excess of blasts in transformation (RAEB-t), and finally, before death, chronic myelomonocytic leukemia with hematologic features similar to those of chronic myelogenous leukemia (CML). The second case, with t(4;11)(p13;p15), progressed from RAEB to acute myelogenous leukemia (M2). In the literature, we found 12 patients with nonlymphocytic leukemia and chromosome abnormalities involving band 11p15, including seven cases with t(7;11)(p13-p15;p15); four cases (including the present case 1) showed CML-like hematologic features. It is suggested that translocations involving 11p15 are a nonrandom chromosome abnormality in nonlymphocytic leukemia.


Persistence of mortgage lending bias in the United States: 80 years after the Home Owners' Loan Corporation security maps.
Housing discrimination and racial segregation have a long history in the United States. The 1930's Home Owners' Loan Corporation (HOLC) "residential security maps," recently digitized, have become a popular visualization of Depression era mortgage lending risk patterns across American cities. Numerous housing policies have since been instituted, including the Home Mortgage Disclosure Act (HMDA), but mortgage lending bias persists. The degree to which detailed spatial patterns of bias have persisted or changed along with urban change is not well understood. We compare historic HOLC grades and contemporary levels of mortgage lending bias using spatially detailed HMDA data. We further examine the relationship between HOLC risk grades and contemporary racial and ethnic settlement patterns. Results suggest that historical mortgage lending risk categorizations and settlement patterns are associated with contemporary mortgage lending bias and racial and ethnic settlement patterns. Concerted and deliberate efforts will be needed to change these patterns.


The motivational drive to natural rewards is modulated by prenatal glucocorticoid exposure.
Exposure to elevated levels of glucocorticoids (GCs) during neurodevelopment has been identified as a triggering factor for the development of reward-associated disorders in adulthood. Disturbances in the neural networks responsible for the complex processes that assign value to rewards and associated stimuli are critical for disorders such as depression, obsessive–compulsive disorders, obesity and addiction. Essential in the understanding on how cues influence behavior is the Pavlovian–instrumental transfer (PIT), a phenomenon that refers to the capacity of a Pavlovian stimulus that predicts a reward to elicit instrumental responses for that same reward. Here, we demonstrate that in utero exposure to GCs (iuGC) impairs both general and selective versions of the PIT paradigm, suggestive of deficits in motivational drive. The iuGC animals presented impaired neuronal activation pattern upon PIT performance in cortical and limbic regions, as well as morphometric changes and reduced levels of dopamine in prefrontal and orbitofrontal cortices, key regions involved in the integration of Pavlovian and instrumental stimuli. Normalization of dopamine levels rescued this behavior, a process that relied on D2/D3, but not D1, dopamine receptor activation. In summary, iuGC exposure programs the mesocorticolimbic dopaminergic circuitry, leading to a reduction in the attribution of the incentive salience to cues, in a dopamine-D2/D3-dependent manner. Ultimately, these results are important to understand how GCs bias incentive processes, a fact that is particularly relevant for disorders where differential attribution of incentive salience is critical.


Optic nerve cysticercosis: case report and review of current management.
The authors present a case of optic nerve cysticercosis in a 32-year-old patient who presented with sudden blurring of vision in the left eye and a transient visual improvement on systemic steroids. The ocular findings were unremarkable other than a relative afferent pupillary defect (RAPD). An ultrasound of the orbit, CT and MRI scans revealed a cystic lesion in the orbital portion of the optic nerve close to the eyeball. A presumed diagnosis of optic nerve cysticercosis was made on the basis of imaging and a positive serum ELISA. The patient improved dramatically on a 4-week therapeutic trial of albendazole and oral steroids. The post-treatment ultrasound and CT scan showed an involution of the cyst with some residual thickening of the optic nerve.


Cardiovascular health and cognitive outcomes: Findings from a biracial population-based study in the United States.
The aim of this study was to evaluate the association of cardiovascular health (CVH) with cognitive outcomes, including incident Alzheimer's dementia, rate of cognitive decline, and measures of brain injury and structure. This study consisted of 1702 Black or African American and White participants living in the south side of Chicago, Illinois, and enrolled in the Chicago Health and Aging Project, a population-based cohort since 1993. CVH was based on seven risk factors, including diet, physical activity, body mass index, smoking, dyslipidemia, hypertension, and diabetes. In a multivariable-adjusted model, CVH was associated with a lower risk of Alzheimer's dementia. The hazard ratio per 1 additional point in CVH score was 0.84 (95% CI 0.76, 0.94). CVH was also associated with a slower rate of cognitive decline and less volume (injury) in white matter hyperintensities. Promoting CVH in communities with Black residents may lower the future risk of Alzheimer's dementia.


Interactions between liposomes and human stratum corneum in vitro: freeze fracture electron microscopical visualization and small angle X-ray scattering studies.
The interactions between three liposomal formulations and human stratum corneum were visualized using freeze fracture electron microscopy. A new replica cleaning method was introduced. Human stratum corneum was submerged for 48 h in liposome suspensions prepared from commercially available phospholipid mixtures. The size, lamellarity and lipid moieties of the liposomes were similar. The main difference between the three phospholipid formulations was the hydrophilicity of the headgroups. The composition dependence of the interactions between these vesicles and human stratum corneum was investigated. In essence, two types of interaction were observed: adsorption of the liposomes on to the outer surface of the stratum corneum, and ultrastructural changes in deeper layers of the stratum corneum caused by mixing of the liposomal constituents and the stratum corneum lipids. The electron microscopic observations were verified with small-angle X-ray scattering. It was found that liposomes composed of phospholipids containing relatively small hydrophilic headgroups showed a marked interaction with the skin lipids of human stratum corneum in vitro. The complexity of the phospholipid mixtures, however, made it very difficult to determine the exact effect each of these headgroups has on the interactions between these vesicles and human stratum corneum.


The design and synthesis of novel alpha-ketoamide-based p38 MAP kinase inhibitors.
We have identified a novel series of potent p38 MAP kinase inhibitors through structure-based design which due to their extended molecular architecture bind, in addition to the ATP site, to an allosteric pocket. In vitro ADME and in vivo PK studies show these compounds to have drug-like characteristics which could result in the development of an oral treatment for inflammatory conditions.


Effect of acute and short-term oral salbutamol treatments on maximal power output in non-asthmatic athletes.
This study aimed to clarify the controversial effects of acute and short-term salbutamol (SAL) intake on sprint performance in healthy athletes. Based on the results of previous studies, an anabolic effect for the short-term treatment and increased glycolysis in both treatments were hypothesized. Eight male recreational athletes completed force-velocity exercise tests after administration of placebo (gelatin), acute oral SAL (6 mg) or short-term oral SAL (12 mg day(-1) for 3 weeks), using a double-blind and randomized protocol. A friction-loaded cycle ergometer fitted with a strain gauge, and an incremental encoder ensured accurate measurement of the force-velocity relationship during sprints. Mechanical data were averaged during each pedal downstroke. Compared with placebo after both acute and 3 weeks of continuous treatment, the force-velocity relationship shifted to the right with power output gains of 14 and 8% (p < 0.001), respectively. This effect was less marked for 3 weeks of continuous treatment compared with acute administration (p < 0.001), suggesting a down-regulation in adrenoceptors. Our first hypothesis thus seems rejected. Significantly higher end-of-exercise and recovery blood lactate concentrations were found under SAL compared with placebo (p < 0.001), supporting our second hypothesis. In conclusion, these data indicate that oral administration of SAL is an effective ergogenic aid for sprint exercise in non-asthmatic athletes. Moreover, an acute treatment seems to be more effective than 3 weeks of continuous treatment.


Immunological variation in Taenia solium porcine cysticercosis: measurement on the variation of the antibody immune response of naturally infected pigs against antigens extracted from their own cysticerci and from those of different pigs.
Although it is widely assumed that both antigen and host immunological variability are involved in the variable intensity of natural porcine infections by Taenia solium (T. solium) cysticercis and success of immunodiagnostic tests vaccines, the magnitude of such combined variability has not been studied or measured at all. In this paper we report statistical data on the variability of the antibody response of naturally infected pigs against the antigens extracted from the vesicular fluids of their own infecting cysts (variance within pigs) and against antigen samples extracted from cysts of other cysticercotic pigs (variance among pigs). The variation between pigs was greater than the inter-pigs variations, which suggests that a concomitant immunity process prevents the establishment of cysts coming from a subsequent challenge. In so doing, we found that there is not a single antigenic band that was recognized by all hosts and that antigens varied among the cysts within the same pigs as well as among pigs. Our results may be valuable for the improvement of immunodiagnostic tests and of effective vaccines against naturally acquired porcine T. solium cysticercosis.


A relative difference in systolic blood pressure between arms by synchronal measurement and conventional cardiovascular risk factors are associated with the severity of coronary atherosclerosis.
It is not known the relationships between a difference in systolic blood pressure (SBP) or diastolic BP (DBP) between arms by synchronal measurement and the presence of coronary artery disease (CAD), and between a difference in BP between arms and the severity of coronary atherosclerosis. We enrolled 425 consecutive patients (M/F = 286/139, 67 ± 13 year) who were admitted to our University Hospital and in whom we could measure the absolute (|rt. BP - lt. BP|) and relative (rt. BP - lt. BP) differences in SBP and DBP using a nico PS-501(®) (Parama-Tech). We divided all patients into those who did and did not have CAD. The relative differences in SBP between arms in patients with CAD were significantly lower than those in patients without CAD. However, the relative difference in SBP between arms was not a predictor of the presence of CAD. We also divided 267 patients who underwent coronary angiography into tertiles according to the Gensini score (low, middle, and high score groups). Interestingly, the middle + high score groups showed significantly lower relative differences in SBP between arms than the low score group. The mean Korotkoff sound graph in the middle + high Gensini score group was significantly higher than that in the low Gensini score group. Among conventional cardiovascular risk factors and nico parameters, the relative difference in SBP between arms in addition to the risk factors (age, gender, body mass index, hypertension, dyslipidemia, and diabetes mellitus) was associated with the score by a logistic regression analysis. In conclusion, the relative difference in SBP between arms as well as conventional risk factors may be associated with the severity of coronary arteriosclerosis.


The effect of pregnancy on the cervical squamocolumnar junction in patients with abnormal cervical cytology.
During a 6 1/2 year study period the author used colposcopy to evaluate 174 pregnant patients with abnormal cervical cytology. Of these patients, 42% had an exocervical squamocolumnar junction. In those patients beyond the age of 25, or with a parity greater than 1, 80% had endocervical junctions. The predominant effect of pregnancy is to stimulate endocervical migration of this junction.


A model for retinal shape changes in ametropia.
Modeling ametropic retinal shape changes with an ellipsoid of constant equatorial radius has been found to produce types of peripheral astigmatism which are in good agreement with experimental findings.


Caring for Children with an Autism Spectrum Disorder: Factors Associating with Health- and Care-Related Quality of Life of the Caregivers.
This study investigated the association of child, caregiver, and caregiving measurements with the quality of life (QoL) in 81 caregivers (mostly parents) of clinically referred children with autism spectrum disorder (ASD). We used the EuroQol five-dimensional (EQ-5D) questionnaire and the care-related QoL questionnaire (CarerQol) to respectively assess health-related QoL and care-related QoL. Health-related QoL was associated with the caregiver's internalizing problems and adaptive coping, explaining 38% of the variance. Parenting stress and adaptive coping were associated with the care-related QoL and explained 60% of the variance. Child variables were not associated with the caregiver's health- and care-related QoL if caregiver and caregiving variables were taken into account. Findings indicate the importance of the caregiver's mental health, coping, and parenting stress in caring for children with ASD.


Factors predicting work status 3 months after injury: results from the Prospective Outcomes of Injury Study.
Few studies examine predictors of work status following injury beyond injuries presenting to a hospital or emergency department. This paper examines the combined influences of socio-demographic, occupational, injury and pre-existing health and lifestyle factors as predictors of work status 3 months after hospitalised and non-hospitalised injury in a cohort of injured New Zealand workers. Prospective cohort study. The Prospective Outcomes of Injury Study, New Zealand. 2626 workforce active participants were identified from the Prospective Outcomes of Injury Study; 11 participants with missing outcome responses were excluded. The primary outcome of interest was 'not working' at the time of interview. 720 (27%) reported 'not working' 3 months after injury. The most important pre-injury predictors of not working following injury found by multidimensional modelling were as follows: low or unknown income, financial insecurity, physical work tasks, temporary employment, long week schedules, obesity, perceived threat to life and hospital admission. Contrary to expectations, workers reporting less frequent exercise pre-injury had lower odds of work absence. Pre-injury psychosocial and health factors were not associated with not working. Certain pre-injury socio-demographic, physical work, work organisation, lifestyle and injury-related factors were associated with not working 3 months after injury. If these findings are confirmed, intervention strategies aimed at improving return to work should address multiple dimensions of both the worker and the workplace.


Adhesion of Denture Characterizing Composites to Heat-Cured, CAD/CAM and 3D Printed Denture Base Resins.
To measure the adhesion of the denture characterizing composite to heat-cured, CAD/CAM and 3D printed denture base resins. Two different denture characterizing composites with different viscosities (SR Nexco; high viscosity (SR) and Kulzer Cre-active; low viscosity (K)) and three denture base resins (Heat cure, CAD-milled and 3D printed) were investigated. 60 beams (25 × 4 × 3 mm) were fabricated for each denture base resin; 30 were bonded to SR and 30 to K to form a beam 50 × 4 × 3 mm. These were further divided (n = 10/group) to simulate the effects of 0, 6, and 12 months intraorally via thermocycling. The beams were subjected to a 4-point bend test using the chevron-notched beam method. Fracture toughness K1C (MPa ·m1/2 ) and flexural bond strength (MPa) were calculated. All specimens were analyzed for the mode of failure under the light microscope and selected specimens under scanning electron microscope. Results were statistically analyzed using ANOVA (SPSS Ver 25). The mean K1C was highest for the SR composite bonded to the heat-cured denture resin group (0.28 ± 0.11), followed by CAD/CAM (0.18 ± 0.04) and 3D printed groups (0.23 ± 0.16). Differences were not statistically significant (p = 0.268). Within each group, aging showed no statistical significance between the mean K1C and flexural bond strength (p = 0.209). The mean K1C for the K composites bonded to the three different denture bases were significantly lower compared to the SR group (p < 0.001). The mean K1C for the heat-cured denture resin group was (0.21 ± 0.1), followed by CAD/CAM (0.13 ± 0.04) and 3D printed groups (0.03 ± 0.02). Within each of the K group, aging showed a statistical significance for both the mean K1C and flexural bond strength (p = 0.002). The high viscosity SR showed significantly higher K1C and flexural bond strength to the lower viscosity K when bonded to heat-cured, CAD-milled and 3D printed denture base resins. Heat-cured denture base resins produced the highest K1C and flexural bond strength when bonded to two different types of characterizing composites.


Global trend of survival and damage of systemic lupus erythematosus: meta-analysis and meta-regression of observational studies from the 1950s to 2000s.
To assess systemically with meta-analysis the trend of survival and its determinants, which are hindering further improvement of survival of patients with systemic lupus erythematosus (SLE) over the past 5 decades. Retrospective, cross-sectional, and prospective observational studies addressing survival and damage in SLE patients published between 1 January 1950 and 31 July 2010 were identified in electronic databases. Using the random-effects model, effect size was calculated based on the logit of the overall 5- and 10-year survival rates. The pooled logit and its robust 95% confidence interval were transformed back into the 5- and 10-year survival rates, after adjusting for potential dependence on the data. Potential factors predicting the pooled survival rates were explored by meta-regression. Seventy-seven studies involving 18,998 SLE patients were analyzed. Between the 1950s and the 2000s, their overall survival significantly increased, from 74.8% to 94.8% and 63.2% to 91.4% for the overall 5-year and 10-year survival, respectively (P < 0.001). The survival improvement, however, appeared to slow down between 1980 and 1990. Meta-regression revealed that neuropsychiatric and renal damage negatively affected the overall 5-year survival, whereas neuropsychiatric damage remained so for the 10-year survival for the past 50 years. Furthermore, the prevalence of neuropsychiatric damage has been significantly increasing over the past 5 decades. For the past 50 years, damage involving the renal and neuropsychiatric systems has been negatively affecting survival of SLE patients. Early detection and aggressive management of renal and neuropsychiatric involvement may potentially improve further the survival of lupus patients.


Plasma motilin levels in duodenal ulcer and effect of a truncal vagotomy and hypoglycaemia.
The identical response of plasma motilin levels, in duodenal ulcer patients and healthy controls, to a test meal and insulin induced hypoglycaemia, fail to demonstrate any significant abnormalities in motilin release. The close correlation between blood glucose and motilin suggest a possible role of this new hormone in carbohydrate metabolism.


The induction of ferroptosis by impairing STAT3/Nrf2/GPx4 signaling enhances the sensitivity of osteosarcoma cells to cisplatin.
Recent studies have indicated that promoting ferroptosis is a promising approach to attenuate drug resistance of cancer cells. Hence, this study aimed to induce ferroptosis in osteosarcoma cells, thereby increasing the sensitivity to cisplatin. Osteosarcoma cells MG63 and Saos-2 were incubated with increasing doses of cisplatin to generate cisplatin-resistant strains, MG63/DDP and Saos-2/DDP. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assays were performed to evaluate cell proliferation and cell death, respectively. Malondialdehyde (MDA), reactive oxygen species (ROS), and lipid oxidation in cells were measured to evaluate the degree of cell ferroptosis. MG63/DDP and Saos-2/DDP cells showed increased viability and decreased death rate compared with MG63 and Saos-2 cells, respectively, upon cisplatin treatment. Western blotting analysis indicated that protein levels of p-STAT3 (Ser727), nuclear factor erythroid 2-related factor 2 (Nrf2), and glutathione peroxidase 4 (GPx4) in drug-resistant strains increased significantly in response to cisplatin. Co-treatment with cisplatin and agonists of ferroptosis, Erastin, and RSL3, remarkably increased MDA, ROS, lipid oxidation, and sensitivity to cisplatin, in MG63/DDP and Saos-2/DDP cells. Similar results were observed by co-treatment of cells with cisplatin and a STAT3 inhibitor. The reduction of protein levels of p-STAT3 (Ser727), Nrf2, and GPx4 in MG63/DDP and Saos-2/DDP cells resulted in increased ferroptosis and sensitivity to cisplatin. These results indicate that cisplatin-resistant osteosarcoma cells inhibited ferroptosis after exposure to low doses of cisplatin. However, ferroptosis agonists and STAT3 inhibitor reactivated ferroptosis in the cells and consequently increased sensitivity to cisplatin. This study demonstrates a new approach to attenuate resistance of osteosarcoma to cisplatin in vitro .


Diminished sensitivity of re-initiation of translation to inhibition by cap analogues in reticulocyte lysates.
In a nuclease-treated reticuloyte lysate reinitiation of protein biosynthesis was less inhibited by 7-methylguanosine 5'-monophosphate (m7GMP), whereas primary-initiation could be totally blocked by cap analogues. We suggest that a cap binding factor binds to mRNA as a first step in initiation of protein synthesis and that this factor remains bound during the subsequent reinitiation cycles. Primarily because of the greater relative importance of the reinitiation process, globin synthesis in the untreated lysate was less inhibited by m7GMP.


Liver transplant with a marginal donor graft containing a hydatid cyst--a case report.
Liver transplantation has become the standard treatment for acute failure and end-stage liver disease, but there are fewer donor organs available than patients on the waiting list. The donor pool may be increased by using marginal donor candidates. Some infectious and metabolic diseases have been transmitted to the recipient via marginal donor grafts. Hydatid cyst disease is rarely transmitted to a recipient from the donor graft. A literature search showed only 2 previous cases of liver transplantation using a donor graft that contains a hydatid cyst. We treated a 19-year-old woman who experienced acute on chronic end-stage liver failure secondary to cryptogenic cirrhosis. The liver graft from a 97-year-old marginal cadaveric donor contained a calcified hydatid cyst. No complication was associated with the hydatid cyst at 3 years after transplantation. The present case shows that donor livers with an inactive, calcified hydatid cyst may be used for emergency liver transplantation after considering the location, size, and relation of the cyst to vascular and biliary structures. The cyst may be resected on the back table with a successful treatment outcome.


Mitochondrial quality control in hepatic ischemia-reperfusion injury.
Hepatic ischemia-reperfusion injury is a phenomenon in which exacerbating damage of liver cells due to restoration of blood flow following ischemia during liver surgery, especially those involving liver transplantation. Mitochondria, the energy-producing organelles, are crucial for cell survival and apoptosis and have evolved a range of quality control mechanisms to maintain homeostasis in the mitochondrial network in response to various stress conditions. Hepatic ischemia-reperfusion leads to disruption of mitochondrial quality control mechanisms, as evidenced by reduced mitochondrial autophagy, excessive division, reduced fusion, and inhibition of biogenesis. This leads to dysfunction of the mitochondrial network. The accumulation of damaged mitochondria ultimately results in apoptosis of hepatocytes due to the release of apoptotic proteins like cytochrome C. This worsens hepatic ischemia-reperfusion injury. Currently, hepatic ischemia-reperfusion injury protection is being studied using different approaches such as drug pretreatment, stem cells and exosomes, genetic interventions, and mechanical reperfusion, all aimed at targeting mitochondrial quality control mechanisms. This paper aims to provide direction for future research on combating HIRI by reviewing the latest studies that focus on targeting mitochondrial quality control mechanisms.


Potential of Lemna minor and Eichhornia crassipes for the phytoremediation of water contaminated with Nickel (II).
Phytoextraction of Nickel (II) in water by two types of aquatic macrophytes (Lemna minor and Eichhornia crassipes) was investigated using synthetic aqueous solutions of NiSO4 at concentrations of 0.5, 1.5 and 2.5 mg/L. The toxic effects of nickel salt in plants were evaluated through the presence of necrosis and chlorosis. The bioconcentration factor, Nickel (II) removal efficiency and kinetics of removal were also calculated. Results of this study show bioconcentration factors higher than 1000, which categorize L. minor and E. crassipes as hyperaccumulators. Besides, L. minor presented a removal percentage higher than 68%, compared to E. crassipes that did not exceed 50% in any of the three concentrations studied. However, E. crassipes showed better resistance to the effects of nickel and obtained a greater removal capacity during the phytoremediation process that lasted for 10 days. In contrast, L. minor suffered necrosis and chlorosis in a concentration-dependent way. Consequently, both macrophytes are sustainable alternatives for nickel removal from contaminated water.


Insurance coverage for weight loss: overweight adults' views.
Given the prevalence of obesity and associated chronic conditions among U.S. adults, wellness benefits are an increasingly popular approach to promoting weight loss. The goal of the study was to assess overweight and obese adults' beliefs about the helpfulness of insurance coverage of weight loss-related benefits, their willingness to pay for such benefits, and whether these opinions differ by individuals' weight or health insurance type. A national survey was fielded in 2012 among non-pregnant, overweight, and obese adults who had seen a primary care provider in the past year (n=600). Descriptive statistics summarized beliefs about which weight loss-related benefits would be helpful, willingness to pay for such benefits, and agreement about whether health insurers should be able to charge more to obese individuals. Multivariable logistic regression was employed to determine whether beliefs differed by weight category or health insurance type. Analyses were conducted in July 2012. The majority (83%) of respondents cited a specific benefit as helpful. Those with private health insurance had a higher probability (89%, 95% CI=86%, 93%) of endorsing any benefit as helpful relative to those with other types of health insurance. Being obese relative to overweight was associated with greater support (57% vs 39%, p<0.05) for preventing health insurers from charging higher premiums to obese individuals. In this sample of overweight adults, a large proportion endorsed the value of weight loss-related benefits offered by health plans. However, only about one third were willing to pay extra for them, and half disagreed with the notion that health plans should charge more to obese individuals. Given evidence of their effectiveness, wellness benefits should be offered to all individuals.


Simultaneous determination of etretinate, acitretin and their metabolites in perfusate, perfusate plasma, bile or hepatic tissue with reversed-phase high-performance liquid chromatography.
Etretinate is a synthetic aromatic retinoid used in the treatment of psoriasis and other disorders affecting the skin. Acitretin is the primary active metabolite of etretinate. The in situ perfused rat liver model was used to study the first-pass hepatic metabolism of etretinate and acitretin and a reliable method of quantifying etretinate and its metabolites was needed. Previously published assays allow for the simultaneous quantitation of etretinate and acitretin in blood or plasma. This paper describes an accurate and reliable reversed-phase HPLC method for the determination of etretinate, acitretin and their metabolites in whole perfusate, plasma, bile and hepatic tissue.


Egg components and offspring survival vary with group size and laying order in a cooperative breeder.
Prenatal resource allocation to offspring can be influenced by maternal environment and offspring value, and affect offspring survival. An important pathway for flexible maternal allocation is via egg components such as nutrients and hormones. In cooperative breeders, females with helpers may increase resource allocation to eggs-'differential allocation'-or reduce it-'load-lightening'. Yet, helper effects on egg composition have been poorly studied. Moreover, it is unknown how helpers' presence modulates laying order effects on egg content and survival. Here, we investigated how maternal allocation varied with group size and laying order in the cooperatively breeding sociable weaver (Philetairus socius). We estimated interactive effects of helpers and laying order on allocation to egg mass, yolk nutrients-yolk mass, proteins, lipids, carotenoids, vitamin A and vitamin E-and hormones-testosterone, androstenedione, and corticosterone. Results concurred with the 'differential allocation' predictions. Females with more helpers produced later-laid eggs with heavier yolks and more lipids, and laid eggs overall richer in lipids. Proteins, antioxidants, and hormones were not found to vary with helper number. We then analyzed how helper number modulated laying order effects on survival. Females with more helpers did not specifically produce later-laid eggs with higher survival, but eggs laid by females with more helpers were overall more likely to fledge. These findings show that some egg components (yolk mass, lipids) can positively vary according to females' breeding group size, which may improve offspring fitness.


Immunohistochemical localization of choline acetyltransferase in the chicken mesencephalon.
Choline acetyltransferase, a specific marker for cholinergic neurons, has been immunohistochemically localized in the mesencephalon and in the caudal diencephalon of the chicken. A complete series of transverse sections through the mesencephalon is presented. In the diencephalon, cholinergic fibers were found in the stria medullaris, the fasciculus retroflexus, and the ventral portion of the supraoptic decussation. The nucleus triangularis and the nucleus geniculatus lateralis, pars ventralis also contained cholinergic fibers. Small cholinergic cell bodies were found in the medial habenula. In the pretectum, cholinergic fibers innervated the nucleus lentiformis mesencephali and the tectal gray. The nucleus spiriformis lateralis also contained cholinergic fibers, while most of the cell bodies in the nucleus spiriformis medialis were cholinergic. In the mesencephalon, labelled fibers were found in the nucleus intercollicularis and in all layers of the optic tectum except the stratum opticum. The highest density of tectal cholinergic fibers was in the stratum griseum et fibrosum superficiale (SGFS), layer f. Radial cells located in SGFS, layer i were also cholinergic. In the isthmic nuclei, cholinergic fibers were found in the pars magnocellularis, while the pars parvicellularis and the nucleus semilunaris contained labelled cells. The oculomotor, Edinger-Westphal, trochlear, and trigeminal motor nuclei all had cholinergic cell bodies. Cholinergic axons were present in the oculomotor and trochlear nerves. In the tegmentum, cell bodies were labelled in the nucleus mesencephalicus profundus, pars ventralis, while the nucleus interpeduncularis had dense cholinergic innervation. Our localization of cholinergic cell bodies and fibers has been compared with earlier autoradiographic and anatomical studies to help define cholinergic systems in the avian brain. For example, the results indicate that the chicken may have a cholinergic habenulointerpeduncular system similar to that reported in the rat. Establishing the cholinergic systems within the avian midbrain is important for designing future neurophysiological and pharmacological studies of cholinergic transmission in this region.


Serum levels of appetite-regulating hormones and pro-inflammatory cytokines are ameliorated by a CLA diet and endurance exercise in rats fed a high-fat diet.
This study examined whether conjugated linoleic acid (CLA) supplementation and endurance exercise affect appetite-regulating hormones and pro-inflammatory cytokines in rats. Seven-week-old male Sprague-Dawley rats were divided randomly into the high-fat diet sedentary group (HS, n=8), the 1.0% CLA supplemented high-fat diet sedentary group (CS, n=8), and the 1.0% CLA supplemented high-fat diet exercise group (CE, n=8). Rats in the CE group swam 60 min/day, 5 days/week for 4 weeks. Leptin and insulin levels in the CS and CE groups were significantly lower than those in the HS group (p<0.001), whereas leptin (p<0.01) and insulin (p<0.05) levels decreased significantly in the CE compared to those in the CS group. Interleukin (IL)-1β (p<0.001) and IL-6 (p<0.01) levels in the CS and CE groups decreased significantly compared to those in the HS group. Leptin (IL-1β: r=0.835, p<0.001), IL-6 (r=0.607, p<0.05), insulin (IL-1β: r=0.797, p<0.01), and IL-6 (r=0.827, p<0.01) levels were positively related with pro-inflammatory cytokine levels. Endurance exercise may play an important role during CLA supplementation of rats on a high-fat diet.


Critical roles of super-enhancers in the pathogenesis of autoimmune diseases.
The super-enhancer (SE) is a cluster of enhancers involved in cell differentiation via enhanced gene expression that determines cell identity. Meanwhile, genome-wide association studies (GWASs) have reported the presence of gene clusters containing single nucleotide polymorphisms (SNPs) susceptible to various diseases. According to cell types, these disease-susceptible SNPs are frequently detected in activated SE domains. However, the roles of SEs in the pathogenesis of various diseases remain unclear. This review first presents various functions of enhancer RNAs (eRNAs) transcribed from SEs. Next, it describes how SNPs and eRNAs are involved in the pathology of each autoimmune disease, with a focus on typical diseases such as rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis. This review aims to describe the roles of SEs in the pathogenesis of autoimmune diseases through multiple interactions of these factors, as well as a future outlook on this issue.


Association between height and hypercholesterolemia in adults: a nationwide population-based study in Korea.
Previous studies reported that stature is inversely related to the risk of cardiovascular disease. However, there is limited evidence on the association between height and lipid profiles. We aimed to examine the association of height with total cholesterol and hypercholesterolemia based on the nationally representative dataset of Korean adults. The data of 13,701 adults aged ≥19 years who participated in the Korea National Health and Nutrition Examination Survey (2013-2015) were used in this nationwide population-based cross-sectional study. Hypercholesterolemia was defined as a serum total cholesterol level ≥ 240 mg/dL or use of lipid-lowering medications. Multivariable linear regression and logistic regression analyses were used to examine the association of height with mean total cholesterol level and odds ratios (ORs) of hypercholesterolemia. Approximately 17% of participants had hypercholesterolemia. Mean total cholesterol levels decreased in the higher quartile (Q) groups of height after adjusting for confounding variables including age, sex, body mass index, smoking status, alcohol consumption, physical activity, income, educational level, hypertension, and diabetes mellitus (P for trend = 0.035). After adjusting for these potential confounding variables, the adjusted ORs of hypercholesterolemia were significantly lower in the Q3 and Q4 groups than in the Q1 group; ORs decreased in the higher quartile groups of height (OR: 0.83, 95% confidence interval: 0.71-0.99 in Q3; 0.81, 0.69-0.95 in Q4, P for trend = 0.007). The association between height (Q4 vs. Q1-Q3) and hypercholesterolemia was stronger in men or individuals without hypertension or diabetes than in women or individuals with such diseases. Height is inversely associated with total cholesterol level and odds of hypercholesterolemia among Korean adults. Childhood environment related to short stature may be associated with hypercholesterolemia and cardiovascular health in adulthood.


Multiple rare-earth magnet bead ingestion in a pediatric liver-small bowel-pancreas transplant recipient: A case report and lessons learned.
Ingestion of rare-earth magnet beads in children has been a public health concern. The potential risk of swallowing multiple magnets is related to magnet attraction to each other, resulting in serious gastrointestinal complications, such as entero-enteric fistula formation, peritonitis, bowel ischemia or necrosis, bowel perforation, and potentially death. We describe the clinical outcome of a 10-year-old child with a liver-small bowel-pancreas transplant who swallowed 26 rare-earth magnetic beads. The patient presented with fever and abdominal pain. Due to difficulty locating the magnets and post-surgical anatomy changes, only 25 magnets were removed endoscopically. After the procedure, she continued to have abdominal distention and fever, leading to further investigation and subsequently an exploratory laparotomy, which confirmed a walled-off perforation. She was treated conservatively with bowel rest and antibiotics, without the need for small bowel graft resection. She recovered well and was eventually discharged on her home enteral feeding regimen. This case emphasizes the importance of taking a good history and having a high index of suspicion to diagnose this dangerous clinical condition, especially in children with an associated predisposing condition for foreign body ingestion, such as developmental delay. Early diagnosis of multiple magnet bead ingestion and prompt detection of its complications in pediatric intestinal transplant recipients could help initiate appropriate intervention and prevent intestinal graft loss.


Are bilobectomies acceptable procedures?
Controversy about operative morbidity and oncologic value of bilobectomy has led to a review of our experience over the past 12 years. The charts of 112 patients (100 men and 12 women with a mean age of 63 years) were reviewed for operative mortality and morbidity and long-term survival. Survival of patients with stage I or stage II disease was compared with that of stage-matched and age-matched groups having right pneumonectomy. Four patients (3.5%) died postoperatively. Nonfatal complications occurred in 55 patients (49%); the most frequent problem was pleural space disease (34%). Survival studies focused on the 96 patients with nonsmall cell bronchogenic cancer (44 in stage I, 32 in stage II, and 20 in stage IIIA). The overall 5-year survival rate was 40%; the 5-year survival rate was similar for stage I and stage II (41% for stage I, 50% for stage II, and 17% for stage IIIA). The incidence of local recurrence was significantly increased after bilobectomy for stage I cancer (chi 2 = 5.066; p < 0.05) compared with pneumonectomy but did not affect 5-year survival. Local recurrence and survival were similar after bilobectomy and pneumonectomy in stage II. These data demonstrate an increased morbidity after bilobectomy. Survival studies demonstrate an increased risk of local recurrence in patients with stage I disease, which might be partly explained by understaging.


Micro-assay to measure the allergenicity of a Kunitz-type soybean trypsin inhibitor toward Balb/c mice by using RBL-2H3 cells.
The allergenicity of a Kunitz-type soybean trypsin inhibitor (KSTI) was investigated by a micro-assay of beta-N-acetylhexosaminidase released from RBL-2H3 cells primed with the anti-KSTI serum. KSTI stimulated the release of beta-N-acetylhexosaminidase from RBL-2H3 cells primed with the antiserum. The response of RBL-2H3 cells to the reaginic activity of the mouse anti-KSTI serum correlates fairly well with that by the passive cutaneous anaphylaxis (PCA) test, the sensitivity of both assays appearing to be similar. These results suggest that measuring the beta-N-acetylhexosaminidase released from RBL-2H3 is a convenient way for studying the allergen or the reaginic activity of a murine serum in place of the PCA test.


Pro-inflammatory cytokines mediating senescence of vascular endothelial cells in atherosclerosis.
Atherosclerosis (AS) is a chronic inflammatory vascular disease, and aging is a major risk factor. The accumulation of senescent vascular endothelial cells (VECs) often leads to chronic inflammation and oxidative stress and induces endothelial dysfunction, contributing to the occurrence and development of AS. Senescent cells can secrete a variety of pro-inflammatory cytokines to induce the senescence of adjacent cells in a paracrine manner, leading to the transmission of signaling of cellular senescence to neighboring cells and the accumulation of senescent cells. Recent studies have demonstrated that several pro-inflammatory cytokines, including IL-17, TNF-α, and IFN-γ, can induce the senescence of VECs. This review summarizes and focuses on the pro-inflammatory cytokines that often induce the senescence of VECs and the molecular mechanisms of these pro-inflammatory cytokines inducing senescence of VECs. Targeting the senescence of VECs induced by pro-inflammatory cytokines may provide a potential and novel strategy for the prevention and treatment of AS.


Reexamination of the acoustic method in measurement of Eustachian tube function.
In order to assess the reliability of the acoustic method in examination of Eustachian tube function, 30 subjects with normal, obstructive or patent tubes were examined twice, by the acoustic method, and by the aerodynamic method which we have developed. The reliability of the aerodynamic method has been confirmed by repeated clinical examinations. 60% of the results of the acoustic method were found to disagree with both the results of the aerodynamic method and the clinical findings of the tested ears. One cause of this disagreement was shown to be the influence of motion accompanying deglutition upon the sound transmission.


Value of routine chest radiography in the medical screening of internationally adopted children.
To assess the value of the routine chest radiography as part of the medical evaluation of newly arrived, internationally adopted children. We evaluated the use of routine chest radiography (CXR) in the medical screening of 1598 internationally adopted children. CXR showed abnormalities in 128 cases: 38 of these findings were already known and/or consistent with obvious clinical signs or symptoms, and 54 had no clinical relevance. In two patients, CXR raised the suspicion of tuberculosis. The routine use of CXR in the screening of internationally adopted children rarely yields new, clinically relevant, information and should be performed on indication only.


Atherosclerosis prevention by nutritional factors: a meta-analysis in small animal models.
Atherosclerosis prevention in small laboratory models has been used as a preclinical stage in the development of functional foods with claimed antiatherogenic properties. However, a high heterogeneity of experimental atherosclerosis models as well as species-specific differences in lipoprotein metabolism could limit the usefulness of these developments. To solve this, we have performed a meta-analysis on the effects of nutritional complements (i.e. less than 2% of diet) with potential antiatherogenic properties in mice, rabbits and hamsters, and compared the outcomes with those obtained in humans. A meta-analysis comprising works dealing with dietary prevention of experimental atherosclerosis (i.e. macroscopic and/or pathological evidences of atheromatosis in aorta) has been performed (n = 110 works). Quality criteria were applied resulting in selection of 16 works comprising 511 animals. Despite high heterogeneity, there is a significant effect of nutritional interventions reducing atheroma globally (mean effect 24.38% (95% CI: 13.24-35.51%) of prevention). In mouse studies (20.64% (95% CI: 8.38-32.90%)) and in rabbits (40.48% (95% CI: 6.73-74.23%)) this effect was significant, in contrast with hamster-based works (95% CI: 13.66-49.48%). Meta-regression showed that reduction of atheroma plaque formation was not linked to changes either in total circulating cholesterol or LDL cholesterol levels. Nutritional addition of selected compounds significantly prevents experimental atheromatosis, but the reproduction of positive effects observed in humans was very limited. These analyses reinforce the need for adequate standardization of atherosclerosis studies in preclinical models and for human intervention trials.


Challenges and Risks in Out-of-Hospital Transport of Patients During the Coronavirus Disease 2019 Pandemic.
Norwegian critical care resources are regionalized making air ambulances transport of suspected or confirmed coronavirus disease 2019 (COVID-19)-positive patients a necessity. We prospectively observed pre- and interhospital transportation of patients with suspected or confirmed COVID-19 in our physician-manned emergency medical services. This was a prospective, observational quality assurance study of primary and secondary missions conducted by 2 Norwegian air ambulances during the COVID-19 pandemic. Forty-one (24.1%) were primary missions, whereas 129 (75.9%) were interhospital transports. Most patients (158 [92.9%]) were transported with ground-based vehicles, and 12 (7.1%) were transported by rotor wing aircrafts. One hundred thirty-four of 170 patients (78.8%) were COVID-19 positive at the time of transportation. The median (interquartile range) fraction of inspired oxygen concentration was 0.60 (0.50-0.80), the positive end-expiratory pressure was 11 cm H2O (8-13.5 cm H2O), and the peak inspiratory pressure was 26 cm H2O (22-30 cm H2O). Some degree of elevated treatment challenge was reported in 157 (87.7%) transports, and in 139 (77.7%), the patient risk was considered elevated. The physician stated that some degree of elevated risk for the provider was elevated in 131 (73.2%) of the transports. The capacity of the physician-manned emergency medical services to safely transfer patients remains essential to maintain resilient critical care capacity, and the perceived elevated risks should be considered in capacity planning.


SGIP1 modulates kinetics and interactions of the cannabinoid receptor 1 and G protein-coupled receptor kinase 3 signalosome.
Cannabinoid receptor 1 (CB1R), a G protein-coupled receptor, plays a fundamental role in synaptic plasticity. Abnormal activity and deregulation of CB1R signaling result in a broad spectrum of pathological conditions. CB1R signaling is regulated by receptor desensitization including phosphorylation of residues within the intracellular C terminus by G protein-coupled receptor kinases (GRKs) that may lead to endocytosis. Furthermore, CB1R signaling is regulated by the protein Src homology 3-domain growth factor receptor-bound 2-like (SGIP1) that hinders receptor internalization, while enhancing CB1R association with β-arrestin. It has been postulated that phosphorylation of two clusters of serine/threonine residues, 425 SMGDS429 and 460 TMSVSTDTS468 , within the CB1R C-tail controls dynamics of the association between receptor and its interaction partners involved in desensitization. Several molecular determinants of these events are still not well understood. We hypothesized that the dynamics of these interactions are modulated by SGIP1. Using a panel of CB1Rs mutated in the aforementioned serine and threonine residues, together with an array of Bioluminescence energy transfer-based (BRET) sensors, we discovered that GRK3 forms complexes with Gβγ subunits of G proteins that largely independent of GRK3's interaction with CB1R. Furthermore, CB1R interacts only with activated GRK3. Interestingly, phosphorylation of two specific residues on CB1R triggers GRK3 dissociation from the desensitized receptor. SGIP1 increases the association of GRK3 with Gβγ subunits of G proteins, and with CB1R. Altogether, our data suggest that the CB1R signalosome complex is dynamically controlled by sequential phosphorylation of the receptor C-tail and is also modified by SGIP1.


Electrochemistry of cyclic alpha-imino carboxylates and their metal complexes: correlation with physiological activity.
Cyclic voltammetry data were obtained for delta 1-pyrroline-2-carboxylate, delta 3-thiazoline-4-carboxylate, delta 2-thiazoline-2-carboxylate and their complexes with Cu(II), Fe(III), and Fe(II). The free ligands were reduced at about -0.35 V and were oxidized in the range of 0.42-0.52 V. Complexing the imine carboxylates with metal ions produces reduction and oxidation in the ranges of 0.05-0.37 V and 0.52-0.74 V, respectively. Prior reports show that these ligands take part in various biological functions. We propose that electron transfer may be involved in some aspects of the physiological activity. The captodative effect can be applied.


The effect of stabilizers and denaturants on the cold denaturation temperatures of proteins and implications for freeze-drying.
The aim of the study is to investigate the effects of stabilizers and denaturants on the thermal and cold denaturation temperatures of selected proteins in systems of interest to freeze-drying. Beta-lactoglobulin and phosphoglycerate kinase (PGK) were chosen as model proteins. Protein thermal and cold denaturation temperatures were determined by both conventional and modulated differential scanning calorimetry and verified by tryptophan emission spectroscopy in selected systems. The cold denaturation of beta-lactoglobulin was reversible, whereas the thermal denaturation was only reversible at high scanning rate (10 degrees C/min). The cold denaturation temperatures of beta-lactoglobulin decreased with an increase in protein concentration (self-stabilization). The cold denaturation temperature increased with increases in pH (from pH 2 to 7) with about 4.6 degrees C increase per unit pH change. All stabilizers studied (i.e., sucrose, trehalose and glycerol) increased the thermal denaturation temperature of the proteins studied and decreased the cold denaturation temperature. The effect of sucrose in decreasing the PGK cold denaturation temperature [40 degrees C per molar concentration increase (40 degrees C/M)] was of the same magnitude as for beta-lactoglobulin (36 degrees C/M). The effect of stabilizers on cold denaturation temperatures is much greater than the effect on thermal denaturation temperatures. With sucrose, the beta-lactoglobulin thermal denaturation temperature increases only about 5 degrees C from 0 to 2.7 M, whereas the decrease in cold denaturation temperature was more than 35 degrees C even at sucrose concentrations as low as 0.9 M. Denaturants (urea and guanidine hydrochloride) increased the cold denaturation temperatures of proteins and thereby destabilized protein; the magnitudes were 9 degrees C/M (urea on Tcd of beta-lactoglobulin) and 65 degrees C/M (guanidine hydrochloride on PGK) compared with literature data of 16 degrees C/M (guanidine hydrochloride on beta-lactoglobulin). The cold denaturation temperatures of beta-lactoglobulin and PGK extrapolated to zero concentration of denaturants were -14 and -26 degrees C, respectively. The protein cold denaturation temperature was pH-, protein concentration-, and additive-dependent. Stabilizers, such as sugars and/or polyols, can stabilize both protein thermal and cold denaturation, whereas the denaturants destabilize protein cold denaturation. The stabilization effect on protein cold denaturation is much larger than on thermal denaturation, a result of great importance in protein freeze-drying.


Clinicopathologic features and prognostic significance of mixed (Low and high-grade) papillary urothelial carcinoma comparison with low and high-grade papillary urothelial carcinoma.
The World Health Organization/International Society of Urological Pathology (2022 WHO/ISUP) classification categorizes noninvasive carcinomas based on the highest grade observed in a pathology sample. According to this classification, a lesion is classified as mixed-grade (MG) if the highest-grade component comprises less than 5% high-grade (HG) carcinoma [14]. This study included 160 cases of low-grade papillary urothelial carcinoma (LGUC) and 160 cases of HG papillary urothelial carcinoma (HGUC), selected randomly. In addition, 160 consecutive and unselected cases of MG papillary urothelial carcinoma (MGUC) were obtained from all bladder transurethral resection specimens diagnosed with papillary urothelial carcinoma between January 2007 and January 2021. The results of the multivariate analysis showed that histologic grade, invasion of the lamina propria, and the presence of carcinoma in situ at presentation were independent prognostic parameters regarding recurrence-free survival (p = 0.002; hazard ratio (HR) = 1.44, 95% confidence interval (CI) = 1.059-1.956, p = 0.02; and HR = 1.76, 95% CI = 1.159-2.684, p = 0.008, respectively). Histologic grade was the only independent prognostic parameter of disease-specific survival (DSS) (p < 0.001). Comparisons between non-muscle invasive (NMI) MGUC and NMI LGUC, as well as between NMI MGUC and NMI HGUC, revealed statistically significant differences in terms of DSS (HR = 0.07, 95% CI = 0.024-0.252, p < 0.001 and HR = 1.59, 95% CI = 1.023-2.460, p = 0.039, respectively). Our study findings demonstrate statistically significant differences regarding DSS between NMI MGUC and NMI HGUC, as well as between NMI MGUC and NMI LGUC. Therefore, we suggested that considering the presence of less than 5% MGUC as a separate category may be appropriate. However, it is important to validate our results in larger cohorts with longer follow-up periods to establish the clinical significance of MGUC and provide guidance for patient management.


Biosynthesis of paf-acether in cultured-mouse mast cells: the role of calcium and G proteins.
We examined the potential role of a guanine nucleotide-binding protein in the biosynthesis of paf-acether (paf) and the release of beta-hexosaminidase during antigenic stimulation of cultured mouse bone marrow-derived mast cells. Unlike pertussis toxin, cholera toxin treatment enhanced the antigen-stimulated production of paf and calcium mobilisation without affecting acetyltransferase activation and cell degranulation. The level of intracellular cAMP doubled in cholera toxin-treated cells. Our data suggest that a cholera toxin-sensitive guanine nucleotide-binding protein is involved in the IgE receptor-mediated signal transduction leading to paf production most probably at the level of Ca2+ influx.


Pharmacokinetics of anticoagulants apixaban, dabigatran, edoxaban and rivaroxaban in elderly Japanese patients with atrial fibrillation treated in one general hospital.
Steady-state plasma concentrations of anticoagulants and the time since the previous administration in mainly outpatients with atrial fibrillation administered standard or reduced doses were analyzed for 110 elderly Japanese subjects (mean age, 76 years) treated with apixaban (2.5 or 5.0 mg twice daily), dabigatran etexilate (110 or 150 mg twice daily), edoxaban (30 or 60 mg once daily) or rivaroxaban (10 or 15 mg once daily) at one general hospital. The pharmacokinetics in patients treated with standard and reduced doses of the four anticoagulants using liquid chromatography-tandem mass spectrometry was compared with the concentration ranges estimated using physiologically based pharmacokinetic modeling. Reduced doses of anticoagulants resulted in relatively small pharmacokinetic variations compared with the standard dose. Statistical analyses revealed that renal impairment is likely not the sole determinant factor for high plasma concentrations of apixaban, dabigatran, edoxaban and rivaroxaban. Patients with atrial fibrillation should be treated with the correct doses of oral anticoagulants as specified in the package inserts (e.g. reduced doses for elderly patients, patients with low body weights and in combination with P-glycoprotein inhibitor drugs) to avoid excessive or insufficient doses of direct oral anticoagulants.


Determination of Ochratoxin A in wine by packed in-tube solid phase microextraction followed by high performance liquid chromatography coupled to tandem mass spectrometry.
Ochratoxin A (OTA), a widely studied mycotoxin, can be found in a variety of food matrices. As its concentration in food is generally low (in the order of μg kg-1), sample preparation techniques are necessary for the analyte purification and pre-concentration in order to achieve the required low detection limits. The separation and detection methods used for OTA analysis should also offer proper sensitivity in order to allow the adequate quantification of the analyte. This manuscript addresses the development of a methodology aiming the analysis of OTA in wine samples by packed in-tube SPME in flow through extraction mode coupled to HPLC-MS/MS. The in-tube SPME set up utilized a PEEK tube packed with C18 particles as the extraction column. The method was optimized by a central composite design 22+3 extra central points, having as factors the percentage of ACN and time in the sample load step. The functionalities of the method were attested and its analytical conditions, enhanced by using 22% of ACN and 6min in the sample load step. Validation of the method was also accomplished prior to analyses of both dry red wine and dry white wine samples. The method demonstrated proper sensitivity, with detection and quantification limits equal to 0.02 and 0.05μgL-1, respectively. Linearity and precision exhibited a 0.996 correlation coefficient and RSD under 6%, respectively. The method proved to be accurate at medium and higher concentration levels with a maximum recovery of 73% at higher concentration levels. OTA was not detected in either dry red and dry white wine samples evaluated in this work. If present, it would be at concentrations lower than the detection and quantification limits established for the proposed method, and considered not a potential danger to human health according to our present knowledge.


Field assessment of the efficacy of Tephrosia vogelii leaf extracts for control of ticks on naturally infested cattle in the field condition.
Tephrosia vogelii (T. vogelii) is a known tropical leguminous herb for fixing nitrogen in the soil and as pesticide properties. Its crude leaf extract was evaluated as a natural acaricide to control ticks on naturally infested traditionally reared cattle in selected areas of Monze District of Zambia. Experimental animals were selected from herds of cattle with poor or no history of any conventional tick control and were divided into six treatment groups of five animals per set which were sprayed with 5, 10, 20 and 40% w/v of T. vogelii leaf extract bio-acaricide solution. A negative control group of five animals were sprayed with ordinary water, while a positive group with a commercial acaricide (Amitraz®) at a recommended dosage of 1:500 dilution. Half-body tick counts then doubled were conducted on each animal, before and at twenty-four hourly intervals of: 24 (1 day), 48 (2 days), 96 (3 days), 192 (4 days), 384 (5 days) and 768 (6 days) after treatment. The observed tick reductions were found to be statistically significant at all treatment levels (p value < 0.001). With this performance, there was evidence to show that the herbal extract was effective against ticks. The results showed significant and sustained efficacy T. vogelii extract from day 2 to day 6 after treatment. There was no significant difference at 5, 10, 20 and 40 w/v in the observed efficacies between low and high concentrations of the bio-acaricide used. We conclude that T. vogelii could be used to spray animals against ticks, especially in low-income communities and also in setups where organic farming is practiced.


Validation of 18F-rhPSMA-7 and 18F-rhPSMA-7.3 PET Imaging Results with Histopathology from Salvage Surgery in Patients with Biochemical Recurrence of Prostate Cancer.
18F-rhPSMA-7, and its single diastereoisomer form, 18F-rhPSMA-7.3, are prostate-specific membrane antigen (PSMA)-targeting radiopharmaceuticals. Here, we investigated their accuracy for the assessment of lymph node (LN) metastases validated by histopathology. Methods: Data from 58 patients with biochemical recurrence of prostate cancer after radical prostatectomy receiving salvage surgery after PET imaging with 18F-rhPSMA-7 or 18F-rhPSMA-7.3 were retrospectively reviewed. Two nuclear medicine physicians reviewed all PET scans and morphologic imaging in consensus. Readers were masked from the results of histopathology. PET and morphologic imaging were correlated with histopathology from resected LNs. Results: In 75 of 150 resected regions in 54 of 58 patients, tumor lesions were present in histopathology. The template-based specificity of PET (18F-rhPSMA-7 and 18F-rhPSMA-7.3 combined) and morphologic imaging was 93.3% and 100%, respectively. However, 18F-rhPSMA-7 and 18F-rhPSMA-7.3 PET detected metastases in 61 of 75 histopathologically proven metastatic LN fields (81.3%) whereas morphologic imaging was positive in only 9 of 75 (12.0%). The positive predictive value was 92.4% for 18F-rhPSMA-7 and 18F-rhPSMA-7.3 PET and 100% for morphologic imaging. 18F-rhPSMA-7 and 18F-rhPSMA-7.3 PET performance was significantly superior to morphologic imaging (difference in the areas under the receiver-operating-characteristic curves, 0.222; 95% CI, 0.147-0.298; P < 0.001). The mean size of PET-positive and histologically confirmed LN metastases was 6.3 ± 3.1 mm (range, 2-15 mm) compared with a mean size of 9.8 ± 2.5 mm (range, 7-15 mm) on morphologic imaging. Conclusion: 18F-rhPSMA-7 and 18F-rhPSMA-7.3 PET offer a high positive predictive value comparable to that reported for 68Ga-PSMA-11 and represent a valuable tool for guiding salvage lymphadenectomy.


Sensitivity to cocaine and amphetamine among mice selectively bred for differential cocaine sensitivity.
Selective breeding of mice for differences in response to a drug offers a powerful means for testing hypotheses regarding underlying mechanisms and relationships between drug-induced behaviors. Starting from a heterogeneous stock of mice, we have selectively bred lines of mice for extreme differences in their locomotor response to 10 mg/kg cocaine HCl. Selection pressure has been maintained for 12 generations and has resulted in two cocaine sensitive (CAHI) and two cocaine insensitive (CALO) lines. Across the generations of selection, the CAHI lines showed progressively greater amounts of cocaine-induced locomotion, with mice from the S12 generation traveling over 21,000 cm/30 min. following 10 mg/kg cocaine. The CALO lines, in contrast, did not substantially diverge from control values until the S8 generation. By generation 12, however, the LO lines traveled no further following 10 mg/kg cocaine (7000 cm/30 min), than they did following an initial saline injection. Cocaine and amphetamine dose-response analyses were conducted on drug-naive mice from the tenth generation. The CAHI lines were extremely sensitive to the locomotor activating effects of all doses of cocaine, displaying from 2- to 6-fold greater amounts of cocaine-induced locomotion than the CALO lines. The CALO lines, in contrast, were completely insensitive to the psychomotor stimulant effects of cocaine. The CAHI lines were also more sensitive to the locomotor activating effects of amphetamine. Both lines showed dose-dependent amphetamine-induced locomotion that peaked at 3 mg/kg. However, at all doses, the CAHI lines showed a 2- to 4-fold greater amount of locomotion than CALO lines. Thus, the sensitivity to cocaine developed through selection using a single dose of cocaine has generalized to a range of doses of cocaine and to at least one other psychostimulant.


Novel R-(+)-limonene-based thiosemicarbazones and their antitumor activity against human tumor cell lines.
In an attempt to develop potent and selective antitumor agents, a series of novel thiosemicarbazones derived from a natural monoterpene R-(+)-limonene was synthesized and their antitumor activity was evaluated. Overall, the majority of tested compounds exhibited considerable inhibitory effects on the growth of a wide range of cancer cell lines. Almost all of tested thiosemicarbazones were especially sensitive to prostate cells (PC-3). Derivatives 5, 6, 8, 9, 10, 11 and 13 presented the most potent antitumor activity against PC-3 cells. These compounds showed lower value of GI50 (0.04-0.05 μM) than the reference drug paclitaxel, besides a high selectivity for the same cell line. The 4-fluorobenzaldehyde derivative 10 was the most selective compound for prostate cells, while 2-hydroxybenzaldehyde derivative 8 was the most active compound, with potent antitumor activity against all tested cell lines.


Altered expression of NCAM in hippocampus and cortex may underlie memory and learning deficits in rats with streptozotocin-induced diabetes mellitus.
Neurological and structural changes are paralleled by cognitive deficits in diabetes mellitus. The present study was designed to evaluate the expression of neural cell adhesion molecules (NCAM) in the hippocampus, cortex and cerebellum and to examine cognitive functions in diabetic rats. Diabetes was induced in male albino rats via intraperitoneal streptozotocin injection. Learning and memory behaviors were investigated using a passive avoidance test and a spatial version of the Morris water maze test. NCAM expression was detected in the hippocampus, cortex and cerebellum by an immunoblotting method. The diabetic rats developed significant impairment in learning and memory behaviours as indicated by deficits in passive avoidance and water maze tests as compared to control rats. Expression of NCAM 180 and 120 kDa were found to be higher in hippocampus and cortex of diabetic rat brains compared to those of control, whereas expression of NCAM 140 kDa decreased in these brain regions. Our findings suggest that streptozotocin-induced diabetes impairs cognitive functions and causes an imbalance in expression of NCAM in those brain regions involved in learning and memory. Altered expression of NCAM in hippocampus may be an important cause of learning and memory deficits that occur in diabetes mellitus.


Community-based child and family services--many questions remain.
In a description of baseline characteristics of experimental and control families that are to be part of an evidence-based intervention study, Sundelin et al. found, contrary to expectations, a negative association between high socio-economic status (SES) and child outcomes. Allowing for possible study limitations, the results of Sundelin et al. further the argument that community-based services should be provided universally to all children and families, rather than attempting to target services on the basis of SES.