Overexpression of GOLPH3 promotes proliferation and tumorigenicity in breast cancer via suppression of the FOXO1 transcription factor.
Golgi phosphoprotein 3 (GOLPH3) has been reported to be involved in various biologic processes. The clinical significance and biologic role of GOLPH3 in breast cancer, however, remains unknown. Expression of GOLPH3 in normal breast cells, breast cancer cells, and 6-paired breast cancer and adjacent noncancerous tissues were quantified using real-time PCR and Western blotting. GOLPH3 protein expression was analyzed in 258 archived, paraffin-embedded breast cancer samples using immunohistochemistry. The role of GOLPH3 in breast cancer cell proliferation and tumorigenicity was explored in vitro and in vivo. Western blotting and luciferase reporter analyses were used to investigate the effect of GOLPH3 overexpression and silencing on the expression of cell-cycle regulators and FOXO1 transcriptional activity. GOLPH3 was significantly upregulated in breast cancer cells and tissues compared with normal cells and tissues. Immunohistochemical analysis revealed high expression of GOLPH3 in 133 of 258 (51.6%) breast cancer specimens. Statistical analysis showed a significant correlation of GOLPH3 expression with advanced clinical stage and poorer survival. Overexpression and ablation of GOLPH3 promoted and inhibited, respectively, the proliferation and tumorigenicity of breast cancer cells in vitro and in vivo. GOLPH3 overexpression enhanced AKT activity and decreased FOXO1 transcriptional activity, downregulated cyclin-dependent kinase (CDK) inhibitor p21(Cip1), p27(Kip1), and p57(Kip2), and upregulated the CDK regulator cyclin D1. Our results suggest that high GOLPH3 expression is associated with poor overall survival in patients with breast cancer and that GOLPH3 overexpression increases the proliferation and tumorigenicity of human breast cancer cells.


Different responses to K-10 and CIDI suggest that complex structured psychiatric interviews underestimate rates of mental disorder in old people.
Epidemiological surveys based on complex diagnostic interviews, such as the Composite International Diagnostic Interview (CIDI), report very low rates of anxiety and depressive disorders in older age groups. Mental health checklists show much less change over the lifespan. This paper explores the possibility that complex interviews present a special challenge to older respondents and thereby exaggerate the decline in mental disorder with age. Analysis of data from an Australian national mental health survey with 10,641 community-resident adult respondents. Measures of interest included ICD-10 anxiety and depression diagnoses, scores on the Kessler Psychological Distress Scale (K-10), agreement between K-10 and CIDI anxiety and depressive questions, and changes in agreement with age. Levels of inconsistency between simple and complex questions about anxiety and depression rose with age. Older people may have difficulty attending to and processing lengthy, complex questionnaires. When in doubt, their preferred response may be to deny having experienced symptoms, thus deflating rates of diagnosed mental disorder. We recommend that simple mental health scales be included in epidemiological studies involving older age groups.


Complement receptors in human renal glomeruli.
Glomeruli in Cryostat sections of foetal and adult renal tissues adsorbed sheep erythrocytes sensitized with IgM antibody and human or mouse complement (EAC). Activated complement was essential for the reaction to occur. The receptor had specificity for the C3b fragment of C3 and is probably of protein or glycoprotein nature. Complement receptors in glomeruli may explain the deposition of complement components or complement-containing complexes in immune-complex glomerulonephritis.


Enhanced atherogenesis and altered high density lipoprotein in patients with Crohn's disease.
A chronic inflammatory state is a risk factor for accelerated atherogenesis. The aim of our study was to explore whether Crohn's disease (CD), characterized by recurrent inflammatory episodes, is also associated with accelerated atherogenesis. In 60 CD patients and 122 matched controls, carotid intima media thickness (IMT), a validated marker for the burden and progression of atherosclerosis, was assessed ultrasonographically. Additional subgroup analyses, including plasma levels of acute phase reactants and HDL protein profiling, were performed in 11 consecutive patients with CD in remission, 10 patients with active CD, and 15 healthy controls. Carotid IMT in patients with CD was increased compared with healthy volunteers: 0.71 (0.17) versus 0.59 (0.14) mm (P < 0.0001), respectively. In the subgroup analysis, HDL levels in controls and patients in remission were identical [(1.45 (0.48) and 1.40 (0.46) mmol/l; P = 0.797], whereas HDL during exacerbation was profoundly reduced: 1.02 (0.33) (P = 0.022). HDL from patients with active CD and CD patients in remission was characterized by a reduced ability to attenuate oxidation compared with controls (P = 0.008 and P = 0.024 respectively). Patients with CD have increased IMT compared with matched controls, indicative of accelerated atherogenesis. The changes during CD exacerbation in terms of HDL concentration and composition imply a role for impaired HDL protection in these patients.


Synaptic input from identified muscle afferents to neurones of the dorsal spinocerebellar tract in the cat.
Single identified group I a and I b muscle afferent fibres were injected with horseradish peroxidase in the lumbar dorsal columns of anaesthetized cats. The morphological details of the axon collaterals and terminal boutons of these muscle afferents within Clarke's column were subsequently reconstructed. The rostro-caudal extent of synaptic terminals from a single afferent fibre within Clarke's column was found to be restricted to less than 1 mm. In the same experiments, dorsal spinocerebellar tract (d.s.c.t.) neurones were retrogradely labelled by injection of horseradish peroxidase into the cerebellum. Synaptic contacts between labelled group Ia and Ib afferent fibres and the soma and proximal dendrites of d.s.c.t. neurones were found. The synaptic contacts from both Ia and Ib fibres varied greatly in size, from 1 X 1 micron up to 'giant' synapses of 20 X 3 micron. Excitatory post-synaptic potentials (e.p.s.p.s) were evoked in d.s.c.t. neurones by impulses in single group I muscle afferent fibres. The fluctuations in peak amplitude of each e.p.s.p. were determined from e.p.s.p. and noise recordings, using a numerical deconvolution procedure. In general, these single-fibre e.p.s.p.s fluctuated between discrete amplitudes separated by an incremental amplitude which was approximately constant. This incremental amplitude did not depend on the average peak amplitude of the particular e.p.s.p. examined. Our anatomical observations of 'giant' boutons arising from Ia and Ib afferent fibres contacting d.s.c.t. neurones raises the possibility of multiple transmitter release sites within an individual synaptic bouton. It is proposed that synaptic transmission between group I muscle afferents and d.s.c.t. neurones occurs with discrete all-or-nothing e.p.s.p.s associated with transmitter release sites.


Transcriptional Modulation by Idelalisib Synergizes with Bendamustine in Chronic Lymphocytic Leukemia.
: The phosphatidyl-inositol 3 kinase (PI3K) δ inhibitor, idelalisib (IDE), is a potent inhibitor of the B-cell receptor pathway and a novel and highly effective agent for the treatment of chronic lymphocytic leukemia (CLL). We evaluated the activities of IDE in comparison to bendamusine (BEN), a commonly used alkylating agent, in primary CLL cells ex vivo. In contrast to BEN, IDE was cytotoxic to cells from extensively-treated patients, including those with a deletion (del)17p. Cross-resistance was not observed between BEN and IDE, confirming their different modes of cytotoxicity. Marked synergy was seen between BEN and IDE, even in cases that were resistant to BEN or IDE individually, and those with deletion (del) 17p. CD40L/interleukin 4 (IL4) co-treatment mimicking the CLL microenvironment increased resistance to IDE, but synergy was retained. PI3Kδ-deficient murine splenic B cells were more resistant to IDE and showed reduced synergy with BEN, thus confirming the importance of functional PI3Kδ protein. Although IDE was observed to induce γH2AX, IDE did not enhance activation of the DNA damage response nor DNA repair activity. Interestingly, IDE decreased global RNA synthesis and was antagonistic with 5,6-Dichlorobenzimidazole 1-b-D-ribofuranoside (DRB), an inhibitor of transcription. These findings add to the increasingly complex cellular effects of IDE, and B cell receptor (BCR) inhibitors in general, in CLL.


Multifocal arterial disease: clinical implications and management.
Vascular disease often affects more than one territory. Atherosclerosis is a global disease affecting multiple organs/systems. Cardiovascular risk factors are associated with an increased risk for the development of arterial disease in all vascular beds but differ in their individual impacts for each vascular bed. We discuss the various options to identify and manage multifocal arterial disease. Coronary artery disease may coexist with carotid artery stenosis, abdominal aortic aneurysms, and/or peripheral artery disease (PAD). Atherosclerotic renal artery stenosis and renal function impairment may complicate PAD. Recent studies have confirmed that patients with multivascular bed disease have higher risk than patients with monovascular disease. In addition to the specific surgical/endovascular therapeutic options available, aggressive medical treatment and vascular disease prevention strategies should be rigorously implemented to best manage the overall atherosclerotic burden. A holistic approach is essential to reduce the cardiovascular morbidity and mortality rates of vascular patients. Preventive measures should complement surgical/endovascular procedures so as to improve outcomes.


Rates of evolution of avirulence phenotypes and DNA markers in a northwest European population of Puccinia striiformis f. sp. tritici.
The effects of evolutionary processes in fungal pathogen populations may occur more rapidly and display larger effects in agricultural systems than in wild ecosystems because of human involvement by plant breeding and crop management. In this study, we analysed the rate of evolution in three lineages of a northwest European population of a biotrophic and asexual reproduced fungal pathogen, Puccinia striiformis f. sp. tritici, causing yellow rust on wheat. Pathogen samples were collected between 1975 and 2002 in the UK and Denmark, and assayed for 14 individual avirulence/virulence alleles and up to 234 amplified fragment length polymorphism (AFLP) primer pairs producing approximately 17,000 AFLP fragments. The large number of fragments and a targeted sampling of isolates allowed a reconstruction of phylogenies in great detail, i.e. no homoplasy and a representation of sequential, evolutionary steps by pathogen samples. A recent, phenotypic loss of avirulence was observed at least once for loci corresponding to P. striiformis f. sp. tritici resistance Yr2, Yr3, Yr4, Yr7, Yr9, and Yr15, whereas Avr6 and Avr17 were lost independently in all three lineages, corresponding to 16 events of loss of avirulence (emergence of virulence). The opposite process, restoration of avirulence, was observed for Yr9 and Yr32. An interpretation of phenotypic changes within lineages as independent mutation events resulted in mutation frequencies from 1.4x10(-6) to 4.1x10(-6) per AFLP fragment (locus) per generation, whereas the effective rate by which a mutation from avirulence to virulence was established in the pathogen population, when subject to selection by host resistance genes, was approximately three orders of magnitude faster.


Impact of walking on eating behaviors and quality of life of premenopausal and early postmenopausal obese women.
Aerobic exercise is known to improve health-related quality of life (QoL). The aim of this study was to compare the effects of a 16-week walking program on eating behaviors and QoL between late premenopausal and early postmenopausal obese and sedentary women, once chronological aging is taken into account. Sixteen women 49 +/- 2 years old and 14 women 53 +/- 2 years old, whose body mass index ranged between 29 and 35 kg/m, were subjected to three sessions per week of 45-minute walking at 60% of their heart rate reserve. Fat mass and lean mass (bioelectrical impedance), cardiorespiratory fitness estimated by maximum oxygen consumption (2-km walking test), eating behaviors (Three-Factor Eating Questionnaire), and QoL, estimated by the Short Form-36 Health Survey, Pittsburgh Sleep Quality Index, and Perceived Stress Scale-10 questionnaires, were recorded before and after exercise. With the exception of a higher attitude of self-regulation in postmenopausal than in premenopausal women (P = 0.05), no between-group differences were observed in body composition, eating behaviors, and QoL at baseline. In all participants, body weight and fat mass decreased, whereas cardiorespiratory fitness increased after walking (0.001 < P < 0.0001). Situational susceptibility was the only eating behavior reduced after training in all women (P = 0.02). Neither the sleep quality index nor the perceived stress score changed in response to endurance exercise. Finally, in all women, Short Form-36 physical and mental scores increased after walking (0.001 < P < 0.05). Despite modest body weight and fat mass losses, a 16-week walking program seems to be sufficient to improve physical and mental well-being, irrespective of menopause status.


A Wireless Pressure Sensor Integrated with a Biodegradable Polymer Stent for Biomedical Applications.
This paper describes the fabrication and characterization of a wireless pressure sensor for smart stent applications. The micromachined pressure sensor has an area of 3.13 × 3.16 mm² and is fabricated with a photosensitive SU-8 polymer. The wireless pressure sensor comprises a resonant circuit and can be used without the use of an internal power source. The capacitance variations caused by changes in the intravascular pressure shift the resonance frequency of the sensor. This change can be detected using an external antenna, thus enabling the measurement of the pressure changes inside a tube with a simple external circuit. The wireless pressure sensor is capable of measuring pressure from 0 mmHg to 230 mmHg, with a sensitivity of 0.043 MHz/mmHg. The biocompatibility of the pressure sensor was evaluated using cardiac cells isolated from neonatal rat ventricular myocytes. After inserting a metal stent integrated with the pressure sensor into a cardiovascular vessel of an animal, medical systems such as X-ray were employed to consistently monitor the condition of the blood vessel. No abnormality was found in the animal blood vessel for approximately one month. Furthermore, a biodegradable polymer (polycaprolactone) stent was fabricated with a 3D printer. The polymer stent exhibits better sensitivity degradation of the pressure sensor compared to the metal stent.


Comprehensive analysis of the prognostic values and immune implication of ESYT3 in lung adenocarcinoma.
Few studies have reported the association between ESYT3 and tumors. The purpose of this study was to investigate the molecular features and potential roles of ESYT3 in lung adenocarcinoma (LUAD). In the present study, GEPIA, UALCAN, TCGA databases, and KM Plotter were primarily used to study ESYT3 mRNA expression profiles and prognostic values in patients with LUAD. Then we evaluated co-expressed genes of ESYT3 by cBioPortal online tools and performed enrichment analysis using Metascape. Moreover, the relationship between ESYT3 and immune infiltrating cells was explored via TIMER2, and MethSurv database was used to conduct methylation analysis. We found ESYT3 was downregulated in LUAD tissues based on TCGA and GEPIA databases. Low expression of ESYT3 mRNA was observed to be significantly correlated with N classification and stage classification. GEPIA2, UALCAN databases and KM Plotter showed that low expression levels of ESYT3 was associated with poor survival in LUAD patients. The enrichment analysis indicated that co-expressed genes of ESYT3 were highly enriched in cell division. Then, our study showed ESYT3 was correlated with immune infiltration and immune checkpoints. Additionally, hypomethylation was associated with low ESYT3 expression and poor prognosis in LUAD. In conclusion, this study suggested ESYT3 could be a potential prognostic marker and a promising therapeutic target in LUAD.


Proteomics analysis of urine and catheter-associated biofilms in spinal cord injury patients.
After spinal cord injury (SCI), use chronic urinary catheters for bladder management is common, making these patients especially vulnerable to catheter-associated complications. Chronic catheterization is associated with bacterial colonization and frequent catheter-associated urinary tract infections (CAUTI). One determinant of infection success and treatment resistance is production of catheter-associated biofilms, composed of microorganisms and host- and microbial-derived components. To better understand the biofilm microenvironment, we performed proteomics analysis of catheter-associated biofilms and paired urine samples from four people with SCI with chronic indwelling urinary catheters. We developed a novel method for the removal of adhered cellular components on catheters that contained both human and microbial homologous proteins. Proteins from seven microbial species were identified including: Escherichia coli, Klebsiella species (spp), Enterococcus spp, Proteus mirabilis, Pseudomonas spp, Staphylococcus spp, and Candida spp. Peptides identified from catheter biofilms were assigned to 4,820 unique proteins, with 61% of proteins assigned to the biofilm-associated microorganisms, while the remainder were human-derived. Contrastingly, in urine, only 51% were assigned to biofilm-associated microorganisms and 4,554 proteins were identified as a human-derived. Of the proteins assigned to microorganisms in the biofilm and paired urine, Enterococcus, Candida spp, and P. mirabilis had greater associations with the biofilm phase, whereas E. coli and Klebsiella had greater associations with the urine phase, thus demonstrating a significant difference between the urine and adhered microbial communities. The microbial proteins that differed significantly between the biofilm and paired urine samples mapped to pathways associated with amino acid synthesis, likely related to adaptation to high urea concentrations in the urine, and growth and protein synthesis in bacteria in the biofilm. Human proteins demonstrated enrichment for immune response in the catheter-associated biofilm. Proteomic analysis of catheter-associated biofilms and paired urine samples has the potential to provide detailed information on host and bacterial responses to chronic indwelling urinary catheters and could be useful for understanding complications of chronic indwelling catheters including CAUTIs, urinary stones, and catheter blockages.


A randomized controlled trial of an mHealth intervention for gay and bisexual men's mental, behavioral, and sexual health in a high-stigma, low-resource context: Project Comunică protocol.
The World Health Organization (WHO) reported that 80% of new HIV diagnoses in 2014 in Europe occurred in Central and Eastern Europe (CEE). Romania has particularly high HIV incidence, AIDS prevalence, and AIDS-related deaths. HIV incidence today in Romania is largely attributed to sexual contact among gay and bisexual men (GBM). However, homophobic stigma in Romania keeps GBM out of reach of the scant available prevention services and serves as a risk factor for HIV. The Comunică intervention delivers motivational interviewing and cognitive-behavioral therapy skills across eight live text-based counseling sessions. Preliminary evidence suggests that Comunică possesses promise for reducing GBM's co-occurring mental (e.g., depression), behavioral (e.g., heavy alcohol use), and sexual (e.g., HIV-transmission-risk behavior) health risks in Romania and perhaps other similar high-stigma national contexts. This paper describes a randomized controlled trial (RCT) designed to test the efficacy of Comunică. To test Comunică's efficacy, 305 GBM were randomized to receive Comunică or a content-matched education attention control condition. The control condition consists of eight time-matched educational modules that present information regarding GBM identity development, information about HIV transmission and prevention, the importance of HIV/STI testing and treatment, heavy alcohol use and its associations with HIV-transmission-risk behavior, sexual health communication, finding social support, and creating sexual health goals. Outcomes are measured pre-intervention (baseline), and at 4-, 8-, and 12-month follow-ups. The primary outcome is frequency of condomless anal sex acts with HIV-positive or unknown-status partners outside of the context of one's own adherent PrEP use or primary partner's adherent PrEP use or undetectable viral load in the past 30 days at each follow-up. Secondary outcomes include depression, anxiety, suicidal thoughts, heavy alcohol use, and HIV/STI testing; motivational and stigma-related mechanisms of intervention efficacy will also be examined. If found to be efficacious, Comunică presents a scalable platform to provide mental, behavioral, and sexual health support to GBM living in Romania and similar high-stigma, low-resource areas within the CEE region and beyond. Registered April 11, 2019 to ClinicalTrials.gov Identifier: NCT03912753.


Expression of autophagy-associated proteins in papillary thyroid carcinoma.
The present study was designed to assess the protein expression of the autophagy-associated genes, Beclin-1 and microtubule-associated protein 1 light chain 3 (LC3)-II, as well as the association with clinicopathological features in papillary thyroid carcinoma (PTC). A total of 50 subjects were recruited, including 50 human PTC samples and paired adjacent noncancerous tissue samples. The protein expression of Beclin-1 and LC3-II was analyzed using immunohistochemistry and western blotting. Beclin-1 and LC3-II expression in PTC tissues significantly reduced compared with normal tissues (P<0.05). Expression of Beclin-1 and LC3-II was associated with lymph node metastasis of PTC (P<0.05), but had no association with age, gender, tumor size, tumor number and Tumor-Node-Metastasis stage (P>0.05). Expression of Beclin-1 and LC3-II were positively correlated (r=0.327;P=0.020) in PTC. In conclusion, the activity of autophagy was declined in PTC; this decrease in autophagic capacity may be associated with tumorigenesis and the development of PTC.


The regulation of masticatory function and food bolus formation.
This review emphasizes the following points: 1. The values of the physiological parameters of mastication (number of cycles and total electromyographic activity in the sequence, sequence duration, cycle frequency in the sequence, kinetic characteristics of the cycles) are characteristic of each individual and vary widely from one individual to another. In a given individual their modification reflects an adaptation of mastication to the size of the food bolus, and the hardness and rheological characteristics of the food. 2. The ready-to-swallow food boluses produced by different individuals nevertheless display similar particle size distributions. 3. Ageing entails adaptation of the masticatory function and does not impair swallowing. 4. Observed increase in total electromyographic activity shows that more energy is expended in mastication by full denture wearers. Despite this increased muscle activity, loss of teeth, even if compensated for by complete dentures, hinders the formation of a normal bolus. The food boluses made by denture wearers thus contain many large-size particles. The impaired mastication observed in denture wearers approaches the masticatory disabilities found in persons with neuromotor deficiencies.


Effect of growth hormone therapy on serum adiponectin and resistin levels in short, small-for-gestational-age children and associations with cardiovascular risk parameters.
Adiponectin and resistin are fat cell-derived hormones, which are thought to be respectively protective and disadvantageous with regard to the development of cardiovascular disease and diabetes mellitus type 2. Low birth weight has been associated with increased risks for the development of these diseases. In short, small-for-gestational-age (SGA) children, GH therapy has several positive effects regarding cardiovascular risk factors. On the other hand, concern has been expressed about the effects of GH therapy on insulin sensitivity. We measured adiponectin and resistin levels in 136 short prepubertal children born SGA and their association with cardiovascular risk parameters and growth factors. Also, we compared the levels with normal-statured controls. The effect of GH treatment was evaluated in 50 short SGA children vs. baseline and vs. an untreated sex- and age-matched SGA control group. Short SGA children had similar adiponectin and lower resistin levels, compared with normal-statured controls. In GH-treated SGA children, neither adiponectin nor resistin levels changed significantly during 2 yr of GH treatment. Compared with untreated sex- and age-matched SGA controls, GH-treated SGA children had similar adiponectin and lower resistin levels. Adiponectin correlated inversely with age but not any cardiovascular risk parameter or growth factor. Higher IGF-I levels in GH-treated children were associated with lower resistin levels. Compared with normal-statured controls, short prepubertal SGA children had similar adiponectin and lower resistin levels. Two years of GH treatment had no effect on their adiponectin and resistin levels.


The effects of the spread of hatch and interaction with delayed feed access after hatch on broiler performance until seven days of age.
Delay in access to feed for 1-d-old chicks impairs posthatch growth. It is a standard practice that 1-d-old chicks are deprived of feed for about 48 h before they are placed on farms. During incubation, there is a spread of 24 to 48 h for late versus early hatching. As spread of hatch increases, number of chicks that are feed-deprived for a longer time before free access (IA) to feed and water increases. In this current study, we investigated the effects of time delay in feed access on chick juvenile relative growth (RG: a measure of speed of growth) up to d 7, taking into consideration the duration of egg storage and spread of hatch. Our results confirmed that delay in feed access caused weight loss during holding time and depressed growth rate after access to feed. The magnitude of the effect depended on the hatching period within the hatching window. It also depended on whether the biological age (BA) or the chronological age (CA) of the chick was considered. Immediate access to feed produced significantly different results depending on CA or BA. Both ways, the method seemed to benefit the late hatchers. This finding contrasts with the effect of delayed feeding in which early hatchers benefited more. Long duration of egg storage depressed RG not only of chicks with immediate access to feed but also in those denied access after hatch. Delay in feed access significantly aggravated the effects of long egg storage duration on RG. Triiodothyronine levels were lower in feed-deprived chicks, and the effect was greater in late hatchers. It is concluded that the beginning of delay in feed access should be determined from the time of hatch not at the end of hatch. It is suggested that the adverse effects of delay in feed access can be reduced by providing a source of energy in hatching baskets or during transportation.


Inorganic analysis using CE: advanced methodologies to face old challenges.
Inorganic species still remain of secondary importance when CE is used as an analytical separation tool. Despite considerable efforts of great many groups over last 20 years, plenty of competition, mostly from ion chromatography and elemental MS, restrains the routine use of CE in inorganic analysis. If there is yet hope clinging to make CE a viable alternative in the field, success would ultimately be attained through research activities on negating the disadvantages and amplifying the advantages of the method. Being the latest update of a series of reviews covering the time period from 1990 to 2010, this paper will comment on how and to what extent these challenges of inorganic CE analysis have been addressed in two recent years.


Ontogeny of somatostatin gene expression in rat diencephalon.
Somatostatin gene expression is first detectable, using in situ hybridization, on the 14th fetal day in rat diencephalon. Other structures expressing somatostatin messenger RNA include the anterior basal periventricular nucleus, amygdalo-hippocampal complex, dorsolateral thalamus and distinct areas in the parieto-frontal cortex. Semiquantitative analysis reveals that somatostatin synthesis increases progressively throughout the last third of fetal life and onto postnatal life.


Total serum lactate dehydrogenase activity in acute Plasmodium falciparum malaria infection.
Lactate dehydrogenase (LDH) activity was assayed in the sera of 76 adult male and 76 adult female patients within the age group of 18-40 years presenting with acute, uncomplicated Plasmodium falciparum malaria infection and a control group of 80 healthy adults within the same age group. Patient selection and pre-qualification were done by simple random sampling of individuals presenting at the Bauchi Specialist Hospital Outpatient Department with a history of fever and malaise within a period of one to eight days, and who were confirmed to be infected with the P. falciparum malaria parasite by microscopical examination of Giemsa-stained thin blood slides. The mean serum LDH activity in male patients was found to be 789.4 +/- 35.0 IU. This activity is significantly higher than the control LDH activity of 247.10 +/- 19.0 IU (p-value is less than 0.05). The mean serum LDH activity among female patients was 634.0 +/- 35.0 IU, which is a relatively higher activity compared to the control LDH activity of 247.10 +/- 19.0 IU (p-value is less than 0.05). The combination of acute hepatocellular injury and red cell haemolysis induced by the invading merozoites may account for the increase in serum LDH activity during this infection. Therefore serum LDH activity is a potentially valuable enzymatic marker of acute, uncomplicated P. falciparum malaria infection, especially in the absence of other complicating diseases known to be associated with the above normal serum LDH activities.


pSTAT5 and ERK exhibit different expression in myeloproliferative neoplasms.
Myeloproliferative neoplasms (MPNs) are clonal hematopoietic progenitor cell disorders characterized by the proliferation of one or more hematopoietic lineages. The classical MPNs include polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) entities. These disorders are characterized by bone marrow morphology typical for each disease, and by the presence of JAK2V617F mutation in the marrow and blood. However, JAK2V617F cannot account for the phenotypic heterogeneity of MPNs because approximately half of all cases of ET and PMF show no evidence of this molecular marker. Therefore, the search for novel markers of these diseases is necessary to improve pathomorphological and molecular diagnostics. This study aimed to investigate the changes in expression patterns of the proteins STAT5 (the signal transducers and activators of transcription 5) and ERK (extracellular signal-regulated kinase) in bone marrow trephine specimens, derived both from patients with wild-type and mutant (V617F) forms of JAK2 kinase. Furthermore, the changes in STAT5 and ERK2 gene expression levels in the same patients were also investigated. The results of our immunohistochemical, immunoblotting and RT-qPCR studies revealed at least four major unique features of three types of MPNs. These include: i) more pronounced expression of phosphoSTAT5 protein in patients with JAK2V617F mutation compared to patients with wild-type of JAK2 kinase ii) different expression pattern of pSTAT5 in the nucleus and the cytoplasm of megakaryocytes and other bone marrow cells; iii) approximately 5-fold higher expression level of STAT5a gene in PV in comparison to patients with PMF and approximately 2-fold higher than in ET patients; iv) different, intracellular expression patterns of ERK2 and ERK1/2 antigens allowed to distinguish each subtype of MPN. These abnormalities in expression patterns of STAT5 and ERK proteins and genes provide some novel molecular features of MPNs and brings us closer to explaining the pathogenesis of MPNs.


Acquisition of an unfamiliar script in story form by young children.
Preschool, first, and third graders heard similar versions of an unfamiliar scriptlike story followed by a novel story, and were tested for immediate and delayed recall. Children more often confused parts of the similar stories with each other than with the novel story, indicating that the similar versions were perceived as belonging to a separate category or script. "Very specific" story items were recalled better in immediate recall, whereas "very general" items were recalled better in delayed recall, suggesting a transition from reproductive to reconstructive recall. Preschoolers showed less evidence of constructive processing than older children, and their performance was more affected by the degree to which story items were schematically organized.


Blockade of the renin-angiotensin system ameliorates apelin production in 3T3-L1 adipocytes.
Angiotensin II (Ang II), the physiologically-active product of the renin-angiotensin system (RAS), has recently been found to be an adipokine secreted by adipocytes. Although Ang II is known to exert its effects via angiotensin II receptor type 1 (AT1R) or type 2 (AT2R), the roles of the two receptors in the adipose tissue are unclear. Apelin, another adipokine, has been found able to restore glucose tolerance in obese and insulin-resistant mice. Because they are both involved in metabolic disorders, there may be an interaction between the two adipokines. To observe the expression of RAS and apelin, 3T3-L1 adipocytes were harvested after 1, 2, 4, and 6 days of differentiation. The RAS blockers captopril (10(-4) M), perindopril (10(-3) M), losartan (10(-4) M), or PD123319 (10(-4) M) were added at day 2 of differentiation and harvested at day 4 and 6, when apelin expression was measured. Expressions of mRNAs were detected by real-time PCR. Production of Ang II and apelin was measured from culture media by ELISA. Cellular lipid droplets were detected by oil-red staining. Our study showed that the mRNA expressions of AGT, renin, ACE1, and AT2R were up-regulated while AT1R mRNA was down-regulated during adipogenesis. Apelin expression increased during adipogenesis, and this increase was further augmented by blocking RAS. RAS blockers also prevented excessive lipid accumulation and the generation of ROS (reactive oxygen species) in differentiating adipocytes. Our study suggests that RAS blockers achieve their beneficial effects by their enhancement of adipocyte secretion of apelin.


Active and latent ovine herpesvirus-2 (OvHV-2) infection in a herd of captive white-tailed deer (Odocoileus virginianus).
Malignant catarrhal fever (MCF) is the clinical manifestation of infection of certain ruminant species with one of a group of pathogenic gammaherpesviruses known as MCF viruses. Cattle and numerous exotic ruminant species are susceptible to clinical disease that may be sporadic or occasionally epidemic in nature. The most common MCF virus worldwide is ovine herpesvirus (OvHV)-2. Reservoir hosts such as sheep, carry and excrete OvHV-2, but do not develop clinical signs, while clinically susceptible species develop severe and often fatal disease. The existence of latent infection in clinically susceptible hosts is poorly understood, but is documented in some ruminant species. Twenty-six animals from a captive herd of white-tailed deer (Odocoileus virginianus) died and were examined from October 2006 to December 2010. Fifteen of these animals (58%) showed clinical signs and gross and microscopical lesions consistent with MCF, while 11 (42%) did not. Polymerase chain reaction (PCR) amplification yielded product consistent with OvHV-2 DNA in samples of spleen from all 26 deer. To examine the possibility of latent infection in this herd, peripheral blood mononuclear cells were examined by PCR for OvHV-2 DNA, and the test was positive in 23/32 (72%) clinically normal deer. Archived serum samples were used to examine the history of MCF exposure in the herd using a competitive enzyme-linked immunosorbent assay, which demonstrated that 10/40 (25%) deer tested had MCF viral antibodies, with nine deer being seropositive over multiple years. Combined with previous observations in deer and other species, these results suggest the existence of latent infection of white-tailed deer with OvHV-2.


Influence of cholestyramine resin administration on single dose sulindac pharmacokinetics.
Cholestyramine, a nonabsorbable anion exchange resin, has been reported to bind concomitantly administered drugs and decrease their bioavailability. The objective of the study was to determine cholestyramine effect on the plasma concentrations of sulindac and its sulfide metabolite following concurrent and staggered (sulindac 3 hours before cholestyramine) dosing. Six healthy volunteers participated in an open-label, 3-way crossover study. Subjects received 400 mg sulindac orally followed by serial blood sampling for sulindac and sulindac sulfide plasma concentrations over a 24-hour period. During the concurrent phase, 4 g of cholestyramine was coadministered resulting in a decrease (p < 0.05) in the area under the curve (AUC) for sulindac compared to sulindac alone (7.11 +/- 3.25 micrograms-h/ml vs 31.65 +/- 7.94 micrograms-h/ml respectively). Also, the sulindac sulfide AUC decreased (p < 0.05) to 7.26 +/- 4.37 micrograms-h/ml coadministration of both drugs compared to 44.69 +/- 11.81 micrograms-h/ml when sulindac is given alone. When the same doses of each drug were given 3 hours apart, the AUC for sulindac (17.88 +/- 3.69 micrograms-h/ml) and its sulfide metabolite (20.12 +/- 7.46 micrograms-h/ml) were still significantly decreased (p < 0.05) when compared to sulindac given alone (31.65 +/- 7.94 micrograms-h/ml for sulindac and 44.69 +/- 11.81 micrograms-h/ml for sulindac sulfide). Based on the lower AUCs for sulindac and sulindac sulfide, separating sulindac and cholestyramine by 3-hour intervals did not prevent the interaction. It is likely that the enterohepatic recycling features of sulindac may not prevent the interaction with cholestyramine even when the 2 drugs are staggered.


An Artificial Intelligence System for Screening and Recommending the Treatment Modalities for Retinopathy of Prematurity.
The purpose of this study was to develop an artificial intelligence (AI) system for the identification of disease status and recommending treatment modalities for retinopathy of prematurity (ROP). This retrospective cohort study included a total of 24,495 RetCam images from 1075 eyes of 651 preterm infants who received RetCam examination at the Shenzhen Eye Hospital in Shenzhen, China, from January 2003 to August 2021. Three tasks included ROP identification, severe ROP identification, and treatment modalities identification (retinal laser photocoagulation or intravitreal injections). The AI system was developed to identify the 3 tasks, especially the treatment modalities of ROP. The performance between the AI system and ophthalmologists was compared using extra 200 RetCam images. The AI system exhibited favorable performance in the 3 tasks, including ROP identification [area under the receiver operating characteristic curve (AUC), 0.9531], severe ROP identification (AUC, 0.9132), and treatment modalities identification with laser photocoagulation or intravitreal injections (AUC, 0.9360). The AI system achieved an accuracy of 0.8627, a sensitivity of 0.7059, and a specificity of 0.9412 for identifying the treatment modalities of ROP. External validation results confirmed the good performance of the AI system with an accuracy of 92.0% in all 3 tasks, which was better than 4 experienced ophthalmologists who scored 56%, 65%, 71%, and 76%, respectively. The described AI system achieved promising outcomes in the automated identification of ROP severity and treatment modalities. Using such algorithmic approaches as accessory tools in the clinic may improve ROP screening in the future.


Newly identified tree shrew cytochrome P450 2B6 (CYP2B6) and pig CYP2B6b are functional drug-metabolising enzymes.
Tree shrews have high phylogenetic affinity to humans and are used in various fields of biomedical research, especially hepatitis virus infection; however, cytochromes P450 (P450s or CYPs) have not been investigated in this species.In this study, tree shrew CYP2B6 and pig CYP2B6b were newly identified and had amino acid sequences highly identical (80% and 78%, respectively) to human CYP2B6, containing sequence motifs characteristic of P450s.Phylogenetic analysis revealed that novel tree shrew CYP2B6 was more closely related to known human CYP2B6 than dog, pig, or rat CYP2Bs are.Among the tissue types analysed, tree shrew CYP2B6 mRNA was preferentially expressed in liver and lung, whereas pig CYP2B6b mRNA was preferentially expressed in jejunum and lung.Tree shrew CYP2B6 and pig CYP2B6b proteins heterologously expressed in Escherichia coli metabolised human CYP2B6 substrates efavirenz, ethoxycoumarin, propofol, and testosterone, suggesting that these novel CYP2Bs are functional drug-metabolizing enzymes in liver and/or lung.


Return to work for individuals with Human Immunodeficiency Virus (HIV) disease: dichotomous outcome variable or personally-constructed narrative challenge?
Advances in the management of HIV disease have increasingly focused attention on the possibilities of return to employment for individuals with HIV disease. However whilst mortality has decreased and life expectancies have lengthened, life for the individual with HIV remains both complex and unpredictable. This article explores the notion of return to work as narrative theme. A case study highlighting the narrative nature of how return to work might be conceptualised by the HIV positive individual is presented; ahead of a brief discussion as to how the lived reality of combination therapy may impact upon the individual's conceptualisation of employment in the broader context of their life story.


Comparison of liver cytology and biopsy diagnoses in dogs and cats: 56 cases.
The results of liver cytology and corresponding biopsy specimens submitted to the Pathology Department at Angell Memorial Animal Hospital during 1998 were retrospectively reviewed to objectively assess the diagnostic value of liver cytology. A "corresponding" biopsy was defined as a biopsy specimen obtained within 1 day of the cytology specimen. Fifty-six cases were reviewed, including 25 from dogs and 31 from cats. Results were in complete agreement in 34 cases, in partial agreement in 11 cases, and in disagreement in 11 cases. Agreement occurred most often in cases of fatty change (10 cases) and neoplasia (7 cases of lymphoma and 3 cases of epithelial tumor). Disagreement was most common in cases of hepatitis (6 cases) in which inflammation was not seen in cytologic specimens. Other causes for disagreement included fibrosis (2 cases), and 1 case each of amyloidosis, hemangiosarcoma, and lymphoma. Three cytologic specimens were considered suggestive of hepatitis because of leukocytosis in the background, although clinicians were advised to compare cytologic observation to CBC results. Cytologic evaluation of the liver was useful for determining disease processes, especially when disease distribution was diffuse.


Characterizing the profiles of patients with acute concussion versus prolonged post-concussion symptoms in Ontario.
Identifying vulnerability factors for developing persisting concussion symptoms is imperative for determining which patients may require specialized treatment. Using cross-sectional questionnaire data from an Ontario-wide observational concussion study, we compared patients with acute concussion (≤ 14 days) and prolonged post-concussion symptoms (PPCS) (≥ 90 days) on four factors of interest: sex, history of mental health disorders, history of headaches/migraines, and past concussions. Differences in profile between the two groups were also explored. 110 patients with acute concussion and 96 patients with PPCS were included in our study. The groups did not differ on the four factors of interest. Interestingly, both groups had greater proportions of females (acute concussion: 61.1% F; PPCS: 66.3% F). Patient profiles, however, differed wherein patients with PPCS were significantly older, more symptomatic, more likely to have been injured in a transportation-related incident, and more likely to live outside a Metropolitan city. These novel risk factors for persisting concussion symptoms require replication and highlight the need to re-evaluate previously identified risk factors as more and more concussions occur in non-athletes and different risk factors may be at play.


Perturbation-based analysis and modeling of combinatorial regulation in the yeast sulfur assimilation pathway.
In yeast, the pathways of sulfur assimilation are combinatorially controlled by five transcriptional regulators (three DNA-binding proteins [Met31p, Met32p, and Cbf1p], an activator [Met4p], and a cofactor [Met28p]) and a ubiquitin ligase subunit (Met30p). This regulatory system exerts combinatorial control not only over sulfur assimilation and methionine biosynthesis, but also on many other physiological functions in the cell. Recently we characterized a gene induction system that, upon the addition of an inducer, results in near-immediate transcription of a gene of interest under physiological conditions. We used this to perturb levels of single transcription factors during steady-state growth in chemostats, which facilitated distinction of direct from indirect effects of individual factors dynamically through quantification of the subsequent changes in genome-wide patterns of gene expression. We were able to show directly that Cbf1p acts sometimes as a repressor and sometimes as an activator. We also found circumstances in which Met31p/Met32p function as repressors, as well as those in which they function as activators. We elucidated and numerically modeled feedback relationships among the regulators, notably feedforward regulation of Met32p (but not Met31p) by Met4p that generates dynamic differences in abundance that can account for the differences in function of these two proteins despite their identical binding sites.


[BNP or NT-proBNP: "that is the question"].
Blood measurements of BNP and NT-proBNP, its catabolite, improve diagnosis for patients admitted to emergency departments with dyspnoea. In this paper, we have compared the BNP to the NT-proBNP for 119 dyspnoeic patients using at random clear clinical status. Among the test group of 119 patients, 57 showed coherent biological results for the 2 markers. These results confirm the final clinical diagnosis. Nine patients with congestive heart failure had abnormally low BNP and NT-proBNP rates. Six of these patients experienced long delays (longer than 48 hours and less than 72 hours) between their admission in emergency and the biological measurement of the natriuretic biomarkers. Three of the other patients could be not only flash OAP cases with a fast growth and a fast normalisation of BNP but also could have existing genetical factors. These genetical factors leading to high variability in BNP synthesis are not related to physiological or cardiac factors. 43 patients showed a mismatch between BNP and NT-proBNP. BNP appeared to be unstable in vitro. The lack of stability in whole blood or plasma samples is increased by sampling in a glass EDTA collection tube and too long delays in transferring the samples from the emergency area and the laboratory in a big hospital. Ten patients showed a mismatch with abnormally high NT-proBNP or false positive results. Among these 10 patients, 5 had renal dysfunction with a high level of creatinine concentration. It is clear that all Diagnostics Manufacturers should now propose different cut-off for natriuretic peptides tests according to the degree of patients' renal impairment.


The relative importance of ecology and geographic isolation for speciation in anoles.
The biogeographic patterns in sexually reproducing animals in island archipelagos may be interpreted as reflecting the importance of allopatric speciation. However, as the forms are allopatric, their reproductive isolation is largely untestable. A historical perspective integrating geology and molecular phylogeny reveals specific cases where ancient precursor islands coalesce, which allows the application of population genetics to critically test genetic isolation. The Anolis populations on Martinique in the Lesser Antilles are one such case where species-level populations on ancient precursor islands (ca 6-8 Myr BP) have met relatively recently. The distribution of the mtDNA lineages is tightly linked to the precursor island, but the population genetic analysis of microsatellite variation in large samples shows no evidence of restricted genetic exchange between these forms in secondary contact. This tests, and rejects, the hypothesis of simple allopatric speciation in these forms. By contrast, Martinique has pronounced environmental zonation, to which anoles are known to adapt. The population genetic analysis shows restricted genetic exchange across the ecotone between xeric coastal habitat and montane rainforest. This does not indicate full ecological speciation in these forms, but it does suggest the relative importance of the role of ecology in speciation in general.


Membrane topology of the multidrug transporter MdfA: complementary gene fusion studies reveal a nonessential C-terminal domain.
The hydrophobicity profile and sequence alignment of the Escherichia coli multidrug transporter MdfA indicate that it belongs to the 12-transmembrane-domain family of transporters. According to this prediction, MdfA contains a single membrane-embedded charged residue (Glu26), which was shown to play an important role in substrate recognition. To test the predicted secondary structure of MdfA, we analyzed complementary pairs of hybrids of MdfA-PhoA (alkaline phosphatase, functional in the periplasm) and MdfA-Cat (chloramphenicol acetyltransferase, functional in the cytoplasm), generated in all the putative cytoplasmic and periplasmic loops of MdfA. Our results support the 12-transmembrane topology model and the suggestion that except for Glu26, no other charged residues are present in the membrane domain of MdfA. Surprisingly, by testing the ability of the truncated MdfA-Cat and MdfA-PhoA hybrids to confer multidrug resistance, we demonstrate that the entire C-terminal transmembrane domain and the cytoplasmic C terminus are not essential for MdfA-mediated drug resistance and transport.


Evidence for endothelium-dependent vasodilation of resistance vessels by acetylcholine.
In the perfused mesenteric arterial vasculature of the rabbit, vasodilation by acetylcholine (ACh) was almost completely blocked after a 15-min perfusion of the vasculature with 0.2% collagenase, an enzyme capable of removing endothelial cells. In the perfused mesenteric arterial vasculature of the rat, vasodilation by ACh was markedly, though not completely, inhibited by hemoglobin (10 microM), an agent which can inactivate endothelium-derived relaxing factor (EDRF). These results suggest that a major component of vasodilation of mesenteric resistance vessels in rabbit and rat by ACh is mediated by EDRF.


Routine chest radiography following imaging-guided placement of tunneled central lines: a waste of time, money, and radiation.
This study sought to evaluate routine chest radiography following placement of tunneled central lines using combined ultrasound and fluoroscopic guidance. A prospective study of 150 consecutive patients who underwent placement of tunneled central lines in the vascular radiology suite. Ultrasound-guided vein puncture was performed with an 18-gauge needle in each case, and the access site was noted. Line position was confirmed by fluoroscopy. Following the procedure, 50 patients had both an on-table digital chest radiograph and a conventional chest radiograph. Subsequent patients had a digital radiograph and a fluoroscopic image grab. Final line tip position was scored, and complications were recorded. Line placement was optimal (95%) or acceptable (5%) in all patients. Line tip position could be satisfactorily evaluated on supine fluoroscopy. Mean fluoroscopic x-ray dose was 0.5 cGy/cm2. Digital chest x-ray dose was 9.0 cGy/cm2, and formal chest radiography dose was 12.0 cGy/cm2. The only complications were 2 carotid artery punctures without clinical sequelae. When lines are placed under imaging guidance with ultrasound to direct the venous puncture, complications are rare and are not likely to be clinically important. Conventional and digital chest radiographs do not contribute clinically relevant information but do add to the radiation dose, time, and expense of the procedure.


The Hydroethanolic Stem Bark Extract of Tieghemella heckelii (A.Chev.) Pierre ex Dubard (Sapotaceae) Produced N-Methyl-D-Aspartate (NMDA) Receptor-Dependent Analgesia and Attenuates Acute Inflammatory Pain via Disruption of Oxidative Stress.
Tieghemella heckelii stem bark is used in African traditional medicine to treat inflammatory pain conditions. However, these biological actions of the plant have not been proven. This study investigates the phytochemical composition and the mechanisms of analgesic and anti-inflammatory actions of the hydroethanolic stem bark extract of T. heckelii (THBE). Phytochemical composition of THBE was investigated using qualitative and quantitative phytochemical analyses. Anti-inflammatory activity was evaluated using the carrageenan-induced paw oedema assay. Analgesic activity was evaluated using hot plate and acetic acid-induced writhing assays. Mechanism of analgesic action was determined using pharmacological antagonist such as naloxone, atropine, flumazenil, nifedipine, or ketamine. Test agents were administered orally as follows: Tween 80 (5%) (control), diclofenac sodium (DS) 10/tramadol 9 mg/kg (standard), or THBE 10, 100, and 450 mg/kg. Glutathione peroxidase (GPx), superoxide dismutase (SOD), and lipid peroxidation levels were also measured. THBE which contained 58.45% saponins, 229.04 ± 0.049 GAE mg/g phenolic compounds,and 0.482 ± 0.0028 QE mg/g flavonoids produced (p < 0.5) anti-inflammatory effect of 56.22% and analgesia of 330 ± 72% and 50.4% in the hot plate and writhing assays, respectively, at 10 mg/kg and inhibited oxidative stress by GPx and SOD elevation in rats during inflammation. Ketamine significantly blocked the analgesia of THBE, indicating NMDA receptor-dependent analgesic action. Whereas, naloxone, atropine, nifedipine, and flumazenil could not antagonize the analgesic action of THBE. These results show that THBE produced potent anti-inflammatory effect via disruption of oxidative stress and also generated NMDA receptor-dependent analgesia.


Dietary cadmium, zinc and copper: effects on chick lung morphology and elastin cross-linking.
Day-old White Leghorn cockerels were divided into seven dietary groups and fed one of the following diets: 1) a casein-based basal diet; 2) a casein-based diet supplemented with 10 mg/kg cadmium, 3) 100 mg/kg cadmium, 4) or 800 mg/kg zinc; 5) a casein-based diet pair-fed to the 100 mg/kg Cd group; 6) a spray-dried nonfat milk-based diet with no added copper, or 7) a spray-dried nonfat milk-based diet supplemented with 5 mg/kg copper. At termination (5 weeks), the birds were killed, and the effects of the diets on selected features of lung composition and morphology were assessed. Body weights were reduced in the 100 mg/kg Cd, pair-fed, and Cu-deficient groups when compared to their controls (casein-based or milk-based copper-supplemented diets). There were no differences in lung weights (expressed relative to metabolic body size) among the groups, although copper deficiency did result in a slight decrease in the dry to wet weight ratio of lung. Lung elastin content and the desmosine content in elastin were significantly lower in the Cu-deficient group and tended to be lower in the group fed 800 ppm Zn. Significant alterations (enlargement of the tertiary bronchial lumen) in morphology were also observed in lungs from both the 100 mg/kg Cd and Cu-deficient groups. Alteration in lung morphology observed in the 100 mg/kg Cd group could not be explained by changes in the elastin content of lung.


Copper-Substituted Lead Perovskite Materials Constructed with Different Halides for Working (CH3NH3)2CuX4-Based Perovskite Solar Cells from Experimental and Theoretical View.
Toxicity and chemical instability issues of halide perovskites based on organic-inorganic lead-containing materials still remain as the main drawbacks for perovskite solar cells (PSCs). Herein, we discuss the preparation of copper (Cu)-based hybrid materials, where we replace lead (Pb) with nontoxic Cu metal for lead-free PSCs, and investigate their potential toward solar cell applications based on experimental and theoretical studies. The formation of (CH3NH3)2CuX4 [(CH3NH3)2CuCl4, (CH3NH3)2CuCl2I2, and (CH3NH3)2CuCl2Br2] was discussed in details. Furthermore, it was found that chlorine (Cl-) in the structure is critical for the stabilization of the formed compounds. Cu-based perovskite-like materials showed attractive absorbance features extended to the near-infrared range, with appropriate band gaps. Green photoluminescence of these materials was obtained because of Cu+ ions. The power conversion efficiency was measured experimentally and estimated theoretically for different architectures of solar cell devices.


Problems of modern urban drainage in developing countries.
Socio-economic factors in developing countries make it more difficult to solve problems of urban drainage than in countries that are more advanced. Factors inhibiting the adoption of modern solutions include: (1) in matters of urban drainage, 19th-century sanitary philosophy still dominates; (2) both legal and clandestine land settlement limits the space that modern solutions require; (3) contamination of storm runoff by foul sewage, sediment and garbage prevents adoption of developed-country practices; (4) climatic and socio-economic factors favour the growth of epidemics where runoff is retained for flood-avoidance and to increase infiltration; (5) lack of a technological basis for adequate drainage management and design; (6) lack of the interaction between community and city administration that is needed to obtain modern solutions to urban drainage problems. Awareness of these difficulties is fundamental to the search for modern and viable solutions appropriate for developing countries.


[Robot-assisted and laparoscopic pyeloplasty.]
Uretero-pelvic junction (UPJ) obstruction has been classically treated by open dismembered pyeloplasty. Recently, laparoscopic (LP) and robotic pyeloplasty (RP) have become the techniques of choice for the treatment of UPJ stenosis in adult and pediatric population. Our objective in this paper is to review the results of minimally invasive surgery as the treatment of UPJ obstruction, the trend to use these approaches and the current limits of LP and RP. A review of most relevant papers and meta-analysis about LP and RP in pediatric and adult population was performed using PubMed. In pediatric population, comparative studies and meta-analysis of relevant series show an overlap of results between LP, RP and open surgery in terms of success rate, rate of complications and hospital stay, being operating time shorter in open pyeloplasty compared to minimally invasive techniques. In infants and pre-school age open surgery remains as technique of choice for pediatric surgeons. In adults, comparative studies and meta-analysis of the most relevant series show also an overlap of results in terms of success rate and complication rate between LP and RP. Nonetheless, minimally invasive techniques seem to offer a significant shortening of hospital stay and need for analgesics compared to open surgery, reason why laparoscopic techniques are recommended over open pyeloplasty in adult population. In view of published literature, minimally invasive surgery has been postulated as the standard treatment in UPJ stenosis, with superimposable results to open surgery. The high cost of robotic approach limits its use in this type of pathology.


Fat emulsion vehicle for intravenous administration of an aqueous insoluble drug.
Formulation of a sterile preparation for the parenteral administration of a water insoluble drug is described. Methyl CCNU was first dissolved in absolute alcohol and slowly added to a fat emulsion, Intralipid. The preparation was found to be stable for eight hours at room temperature and seven days under refrigeration. After administration of the preparation to approximately 100 patients, no significant side effects were attributed to the fat emulsion.


Ajoene exerts potent effects in 3T3-L1 adipocytes by inhibiting adipogenesis and inducing apoptosis.
This paper describes effects of several sulfur-containing compounds from garlic on the cell viability, apoptosis and adipogenesis in 3T3-L1 adipocytes. In both preadipocytes and mature adipocytes, 100 and 200 microM ajoene significantly decreased cell viability and increased apoptosis. The effect on apoptosis was further confirmed with Hoechst staining. In contrast, diallyl sulfide, diallyl disulfide, diallyl trisulfide, deoxyalliin, and allyl methyl sulfide had no significant effect on cell viability or apoptosis in either preadipocytes or mature adipocytes. In maturing preadipocytes ajoene significantly decreased lipid accumulation in a dose-dependent manner and these results were further confirmed by a decrease in lipid droplet number and lipid content through Oil Red O staining. There was no significant change in lipid accumulation in maturing preadipocytes treated with other garlic derivatives. Thus, despite the same source of origin, garlic, ajoene was the only one with potent effects on cell viability, apoptosis and adipogenesis in 3T3-L1 adipocytes.


The role of Rel/NF-kappaB transcription factors in B lymphocyte survival.
Among the transcriptional mediators of the various signal transduction pathways that have been shown to regulate lymphocyte apoptosis, Rel/NF-kappaB transcription factors have emerged as key regulators of B cell survival during their differentiation and in their activation by antigens or mitogens. The aim of this review is to bring together recent findings on Rel/NF-kappaB regulation of B cell survival and to present an integrated model of how these transcription factors control apoptosis in a signal and differentiation-stage specific manner. In addition to providing a contemporary view of Rel/NF-kappaB regulated B cell survival, the model described here is aimed to serve as a paradigm for how Rel/NF-kappaB family members control survival in different cell types during differentiation and in response to the plethora of signals that impinge on this master transcriptional regulatory pathway.


Repertoire of Protein Kinases Encoded in the Genome of Takifugu rubripes.
Takifugu rubripes is teleost fish widely used in comparative genomics to understand the human system better due to its similarities both in number of genes and structure of genes. In this work we survey the fugu genome, and, using sensitive computational approaches, we identify the repertoire of putative protein kinases and classify them into groups and subfamilies. The fugu genome encodes 519 protein kinase-like sequences and this number of putative protein kinases is comparable closely to that of human. However, in spite of its similarities to human kinases at the group level, there are differences at the subfamily level as noted in the case of KIS and DYRK subfamilies which contribute to differences which are specific to the adaptation of the organism. Also, certain unique domain combination of galectin domain and YkA domain suggests alternate mechanisms for immune response and binding to lipoproteins. Lastly, an overall similarity with the MAPK pathway of humans suggests its importance to understand signaling mechanisms in humans. Overall the fugu serves as a good model organism to understand roles of human kinases as far as kinases such as LRRK and IRAK and their associated pathways are concerned.


Pleural flap for treating perigraft leak after a modified Blalock-Taussig shunt.
Plasa oozing through the graft after a modified Blalock-Taussig shunt is a troublesome complication. We encountered a massive leak following a modified Blalock-Taussig shunt in a 2 1/2 year-old-girl which required reexploration. The leak was treated by wrapping the polytetrafluoroethylene shunt with the parietal pleura flap harvested from the adjacent chest wall. The patient had an uneventful recovery. Covering of the polytetrafluoroethylene shunt with parietal pleura appears to stop plasma leak through the graft following a modified Blalock-Taussig shunt.


Gonorrhea in adolescents: complement-fixing antibodies in a selected population of young women.
Over a four-year period a group of 209 young women committed to a state institution for deliquent youths was screened for infection with Neisseria gonorrhoeae by multiple bacteriologic cultures and by gonococcal complement-fixation tests. In this selected population of sexually active young women with a relatively high prevalence of gonorrhea, the gonoccal complement fixation test proved too insensitive to justify primary reliance on it for the identification of cases of actual disease. Only 25 (38%) of infected women had reactive sera. The specificity of the test was somewhat better; in two cases unexpected sero-positivity led to the identification, and treatment of previously-missed asymptomatic disease.


Nevirapine-related adverse events among children switched from efavirenz to nevirapine as compared to children who were started on nevirapine-based antiretroviral therapy directly.
In this retrospective study, incidence of nevirapine (NVP) toxicity in children who were switched from efavirenz (EFV) to NVP (treatment experienced [TE] group) was compared with that of children who had started NVP-based antiretroviral therapy directly (treatment naïve [TN] group). This study also identified risk factors associated with development of NVP toxicity in children. The incidence and risk of developing NVP toxicities were significantly higher in TE when compared to TN group. Median duration of onset of NVP toxicity from the initiation was 2.14 and 3.84 weeks in TE and TN children, respectively. Mean CD4 count was found to be significantly higher in children who developed toxicity (577 ± 81 cells/µL) as compared to the children who did not develop toxicity (403 ± 29 cells/µL). Similarly, children in TE group who developed NVP toxicity had higher mean CD4 cell count than children in TN with NVP toxicity. The risk factors for the development of NVP toxicity include female gender with CD4 count >250 cells/μL and TE children especially girls with CD4% >15% and boys with CD4 count >400 cells/μL. To conclude, the higher incidence of NVP toxicity among TE group warrants a cautious approach while switching the NVP- from EFV-based therapy.


Therapeutic Agents in Alzheimer's Disease Through a Multi-targetdirected Ligands Strategy: Recent Progress Based on Tacrine Core.
Alzheimer's Disease (AD) is one of the most common forms of dementia in elderly people. To date, efficacious therapeutic agent for the treatment of AD is still very limited, so it has long been a challenging and attractive task to discover new anti-AD drugs. Considering the multifactorial nature of AD, recently, the concept of Multi-Target-Directed Ligands (MTDLs) has emerged as a new strategy for designing therapeutic agents on AD. MTDLs are believed to exert their effects through simultaneously affecting multiple targets which contribute to etiology of AD. Therefore, MTDLs are considered to be more efficacious than mono-target agents. Tacrine is the first drug approved by Food and Drug Administration (FDA). Although the clinical use of tacrine is restricted because of its hepatotoxicity, the high Ligand Efficiency (LE) of this compound makes it an ideal component for designing MTDLs. This article provides an update review of the advances on the development of MTDLs based on tacrine. Case studies are carefully selected to show the detailed strategy on medicinal modification of Tacrine-Based MTDLs. Finally, several concerns and opinions on designing new MTDLs are discussed as well.


Irregular absorption profiles observed from diclofenac extended release tablets can be predicted using a dissolution test apparatus that mimics in vivo physical stresses.
The prediction of the in vivo drug release characteristics of modified release oral dosage forms by in vitro dissolution tests is a prerequisite for successful product development. A novel dissolution test apparatus that mimics the physical conditions experienced by an oral formulation during gastrointestinal transit was developed. This included the simulation of pressure forces exerted by gut wall motility, shear forces generated during propagation, and loss of water contact when the dosage form is located in an intestinal air pocket. The new apparatus was evaluated using a diclofenac extended release (ER) tablet. The in vitro dissolution profiles were compared between the novel test apparatus and a conventional dissolution apparatus (USP II). These data were compared with the profiles of plasma concentration versus time that were obtained after the administration of an ER tablet to 24 healthy volunteers under fasting conditions. Multiple peaks were observed in individual plasma concentration-time profiles after the intake of the reference ER tablet. Standard dissolution testing showed typical characteristics of an almost continuous release for this formulation; however, dissolution testing with the novel apparatus suggested that the diclofenac release from the ER tablets would be extremely variable and dependent on the applied stress. The data suggest that the observed multiple peaks of plasma concentration after dosing of the ER diclofenac tablets are most probably caused by sensitivity to physical stress events during gastrointestinal transit.


[National consensus for management of community acquired pneumonia in adults].
Community acquired pneumonia (CAP) is an acute respiratory infection that affects pulmonary parenchyma, and is caused by community acquired microorganisms. In Chile, pneumonia represents the main cause of death due to infectious diseases and is the third specific cause of mortality in adults. In 1999, an experts committee in representation of "Sociedad Chilena de Enfermedades Respiratorias", presented the first National Guidelines for the Treatment of Adult Community Acquired Pneumonia, mainly based in foreign experience and documents, and adapted it to our National Health System Organization. During the last decade, impressive epidemiological and technological changes have occurred, making the update of guidelines for treatment of NAC by several international scientific societies, necessary. These changes include: new respiratory pathogens that are being identified in CAP and affect adult patients (Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella pneumophila); the increasing senescent adult population that carries multiple co-morbidities; the emergence of antimicrobial resistance among respiratory pathogens associated to massive antibiotic prescription; the development by the pharmaceutical industry of new drugs that are effective for pneumonia treatment (macrolides, ketolides and respiratory fluorquinolones); and the development of new diagnostic techniques for detection of antigens, antibodies, and bacterial DNA by molecular biology, useful in respiratory infections. Based on these antecedents, an Advisory Committee of "Sociedad Chilena de Enfermedades Respiratorias" and "Sociedad Chilena de Infectología" has reviewed the national and international evidence about CAP management in adults in order to update clinical recommendations for our country.


Tandem synthesis of 4-aminoxanthones is controlled by a water-assisted tautomerization: a general straightforward reaction.
Aminoxanthones constitute a group of therapeutically promising compounds that so far have been synthetically challenging. Here, we report the synthesis of both aminodihydroxanthones and fully aromatized aminoxanthones by an easy to perform, one-step multicomponent reaction of isocyanides, 3-carbonylchromones and dienophiles. The mechanism of the reaction involves a sequence of a [4 + 1] cycloaddition, iminolactone-aminofuran tautomerization, [4 + 2] cycloaddition, oxygen ring opening and aromatization. Remarkably, DFT quantum chemical computations revealed that the iminolactone-aminofuran tautomerization requires the assistance of a water molecule and, contrary to intuition, it is the rate-determining step. Conversely, both the [4 + 1] and the [4 + 2] cycloadditions have relatively low calculated energy barriers, regardless the substituents on the starting materials. Thus, we have stablished a straightforward and a wide-ranging synthesis of diversely substituted xanthones. This highly convergent process has also been applied to the synthesis of biologically important chromenophenantridines and secalonic acid related xanthone dimers.


Effect of extracellular fluid volume depletion on renal regulation of acid-base and potassium equilibrium during prolonged mineral acid administration.
Previous studies of the renal and systemic acid-base response to prolonged administration of mineral acids in dogs have suggested that during the steady state of acidosis, the level at which plasma bicarbonate concentration is regulated by the kidney is dependent on the degree of augmentation of "distal delivery" of sodium imposed by the increased filtered load of administered mineral acid anion with filtered sodium, and on the degree of augmentation of "distal avidity" for sodium reabsorption imposed by ECF volume ( ECFV ) contraction secondary to renal sodium losses accompanying the administered mineral acid anion. This formulation, however, fails to predict the level at which plasma bicarbonate concentration would be regulated under conditions of preexisting ECFV depletion, which would simultaneously limit distal delivery of sodium salts and yet increase distal avidity for sodium reabsorption. Our studies assessed the renal and systemic acid-base responses to prolonged daily administration of 5.0 mEq/kg of H+ as HCl (groups 1 and 2) or H2SO4 (groups 3 and 4) in dogs with normal ECFV (groups 1 and 3) vs. preexisting ECFV depletion (groups 2 and 4) induced by administration of ethacrynic acid. In response to HCl administration, dogs with depleted ECFV developed more severe acidosis than ECFV -replete dogs (delta[HCO-3,]p, -5.0 +/- 0.6 mEq/L, group 2 vs. -2.7 +/- 0.5 mEq/L, group 1, p less than 0.02). The exacerbated metabolic acidosis in group 2 persisted in the steady state, even though the steady-state net systemic acid load was not greater than in group 1. No exacerbation of acidosis was observed in H2SO4-fed dogs with depleted ECFV . In response to either HCl or H2SO4, persistent hypokalemia caused by increased renal potassium clearance occurred in ECFV -replete dogs but not in ECFV -depleted dogs. Our results indicate that preexisting ECFV depletion results in impaired renal hydrogen ion secretion during prolonged HCl feeding, but not during H2SO4 feeding. These results suggest that during prolonged HCl loading under conditions of preexisting ECFV depletion, hypovolemia-mediated restriction of the normal augmentation of distal delivery of sodium salts overrides the effects of enhanced distal cation secretory capacity that attends hypovolemia-mediated augmentation of distal avidity for sodium reabsorption.


Inhibitory effect of lactoferrin on in vitro growth of Babesia caballi.
Lactoferrin (LF) is an important biologic molecule with many functions, one of which is antimicrobial defense. We evaluated the growth-inhibiting effects of four types of LF (native LF, Fe(+3)-bound [holo] LF, Fe(+3)-free [apo] LF, and LF hydrolyzate) on the in vitro growth of Babesia caballi and B. equi. The growth of B. caballi was significantly suppressed in media containing apo LF, but was not inhibited in media containing native LF, holo LF, or LF hydrolyzate. The growth of B. equi was not inhibited by media containing native LF, holo LF, or apo LF. These data indicate that apo LF had the strongest inhibitory effect on B. caballi. This may have been caused by inactivation or inhibition of a growth factor in the culture medium.


Multidisciplinary approaches: esthetic restorations after orthodontic treatment.
After orthodontic treatment prosthetic restorations are sometimes still necessary to improve the patient esthetics. After routine orthodontic procedures (alignment of teeth and achievement of functional occlusion) conventional crowns and bridges are used. In this case study, the follow-up results of four patients are presented. They had been treated by various disciplines; orthodontics, plastic surgery and prosthodontics. Satisfactory esthetics and function were achieved with all patients.


[EPIDEMIOLOGICAL FEATURES OF PAPILLOMAVIRUS INFECTIONS AND CERVICAL CANCER IN THE REPUBLIC OF BASHKORTOSTAN AND THE KALININGRAD REGION].
In the context of improving cancer prevention programs, it becomes relevant to justify the introduction of regional HPV cervical cancer screening programs based on a study of the prevalence of human papillomavirus infection and cervical cancer. Aim: to identify the main patterns of the prevalence of human papillomavirus infection and cervical cancer in Bashkortostan and the Kaliningrad region for the scientific substantiation of the criteria for the adoption of regional screening programs. A prospective analytical cohort single-stage observational examination of 3428 women of the Republic of Bashkortostan and 1246 women of the Kaliningrad region was carried out, as well as a retrospective observational analytical study of cervical cancer incidence in Bashkiria and the Kaliningrad region according to the official statistics from 2011 to 2020 compared to Russian indicators. In Bashkortostan and the Kaliningrad region, HPV DNA was detected in 48.7% and 54.2% of women of reproductive age, respectively, of which HPV of high oncogenic risk (HPV HR) was 51.7 ± 6.2%, and 23.4% were found to have PCM . In the Kaliningrad region, HPV DNA was detected in 47.2% of the women under study, HPV VR - 31.1%, in 25.5% accompanied by cervix uteri diseases. An increase in the incidence is noted in the Kaliningrad region by 38.6% over 10 years, with an annual increase of 3.8%. In Bashkortostan, the growth is demonstrated by 31.8% with an annual increase of 3%, which is significantly higher than in the Russian Federation (13.3%, р=0.001). For 10 years, the prevalence of cervical cancer has increased in the Kaliningrad region by 10.1%, with an average annual increase of 1.1%. In Bashkortostan, the prevalence of CSM increased by 4.7% with an annual increase of 0.3%. The high prevalence of HPV infection among women of reproductive age, the unfavorable dynamics of indicators of cervical HPV-associated oncopathology in remote regions of the Russian Federation (Bashkiria and the Kaliningrad region) is a scientifically based criterion for the reorganization of regional cervical screening programs. The implementation of Organized screening with primary HPV examination with mandatory separate genotyping of types 16 and 18 and the remaining 12 types of HPV HRC in a complex will enhance the effectiveness of ongoing preventive measures and meet international standards.


A prospective study on the added value of pulsed arterial spin-labeling and apparent diffusion coefficients in the grading of gliomas.
The purpose of this study was to determine whether qualitative and quantitative measures obtained with pulsed arterial spin-labeling (PASL) and apparent diffusion coefficients (ADC) improve glioma grading compared with conventional MR images. We prospectively performed 2 qualitative consensus reviews in 33 suspected gliomas: 1) conventional MR images alone and 2) conventional MR images with PASL and ADC. To calculate the diagnostic performance parameters of PASL and ADC, we used a qualitative scoring system on the basis of the tumor perfusion signal intensity (sTP) and visual ADC scoring (sADC). We then analyzed quantitative regions of interest and calculated the ratio of the maximum tumor perfusion signal intensity (rTPmax) and the minimum ADC value (mADC). Two observers diagnosed accurate tumor grades in 23 of 33 (70%) lesions in the first review and in 29 of 33 (88%) lesions in the second review. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for determining a glioma grading by using combined sTP and sADC scoring were 90.9, 90.9, 95.2, and 83.3%, respectively. Statistical analysis gave a threshold value of 1.24 for rTPmax and 0.98 x 10(-3) mm/s(2) for mADC to provide a sensitivity, specificity, PPV, and NPV of 95.5, 81.8, 91.3, and 90.1% and 90.9, 81.8, 90.9, and 81.8%, respectively. The receiver operator characteristic curve analyses showed no significant difference between the quantitative and combined qualitative parameters. PASL and ADC significantly improve the diagnostic accuracy of glioma grading compared with conventional imaging.


Demineralized dentin and enamel matrices as suitable substrates for bone regeneration.
In recent decades, tooth derivatives such as dentin (D) and enamel (E) have been considered as potential graft biomaterials to treat bone defects. This study aimed to investigate the effects of demineralization on the physical-chemical and biological behavior of D and E. Human D and E were minced into particles (Ø<1 mm), demineralized and sterilized. Thorough physical-chemical and biochemical characterizations of native and demineralized materials were performed by SEM and EDS analysis and ELISA kits to determine mineral, collagen type I and BMP-2 contents. In addition, MG63 and SAOS-2 cells were seeded on tooth-derived materials and Bio-Oss®, and a comparison of cell responses in terms of adhesion and proliferation was carried out. The sterilization process, as a combination of chemical and thermal treatments, was found to be effective for all materials. On the other hand, D demineralization allowed preserving the collagen content, while increasing BMP-2 bioavailability. D and demineralized D (dD) displayed excellent biocompatibility, even greater than Bio-Oss®. Conversely, the high mineral content displayed by E, as confirmed by EDS analysis, inhibited cell proliferation. Of note, even though the demineralization process was somehow less effective in E than in D, demineralized E (dE) displayed increased BMP-2 bioavailability and improved performance in vitro compared with native E. Our results substantiate the idea that the demineralization process lead to an increase of BMP-2 bioavailability, thus paving the way toward development of more effective, osteoinductive tooth-derived materials for bone regeneration and replacement.


Digital technology adoption in livestock production with a special focus on ruminant farming.
Digitalisation is an integral part of modern agriculture. Several digital technologies are available for different animal species and form the basis for precision livestock farming. However, there is a lack of clarity as to which digital technologies are currently used in agricultural practice. Thus, this work aims to present for the first time the status quo in Swiss livestock farming as an example of a highly developed, small-scale and diverse structured agriculture. In this context, the article focuses on the adoption of electronic sensors and measuring devices, electronic controls and electronic data-processing options and the usage of robotics in ruminant farming, namely, for dairy cattle, dairy goats, suckler cows, beef cattle and meat-sheep. Furthermore, the use of electronic ear tags for pigs and the smartphone usage for barn monitoring on poultry farms was assessed. To better understand the adoption process, farm and farmer's characteristics associated with the adoption of (1) implemented and (2) new digital technologies in ruminant farming were assessed using regression analyses, which is classified at a 10% adoption hurdle. The results showed clear differences in the adoption rates between different agricultural enterprises, with both types of digital technologies tending to be used the most in dairy farming. Easy-to-use sensors and measuring devices such as those integrated in the milking parlour were more widespread than data processing technologies such as those used for disease detection. The husbandry system further determined the use of digital technologies, with the result that farmers with tie stall barns were less likely to use digital technologies than farmers with loose housing systems. Additional studies of farmers' determinants and prospects of implementation can help identify barriers in the adoption of digital technologies.


[Determination of SiO2 in Groundwater and Mineral Water by Inductively Coupled Plasma-Atomic Emission Spectrometry].
The concentration of silica in groundwater and mineral water was determined by inductively coupled plasma-atomic emission spectrometry (ICP-AES). After a more sensitive analytical line of silicon was chosen, the effects of operating conditions of the ICP spectrometer on the analysis results were investigated, at the same time, the impact of coexisting ions on determination results of SiO2 was also considered and eliminated. The transmit power of 1 350 W, observation height of 12 mm, the nebulizer pressure of 0. 20 MPa and the pump speed of analysis of 75 r . min-1 were selected by experimental conditions. Under the optimum analytical conditions of spectrometer, the method was used for the determination of SiO2 in groundwater and mineral water with the detection limit of 0. 017. mg . L-1, recoveries between 94. 10% and 103. 8%, and relative standard deviation (RSD)s≤3. 06%. Compared with the results of silicon molybdenum yellow spectrophotometry, the results were basically consistent with the relative deviation ≤3. 00%. In conclusion, the method is simple and efficient with high precision and accuracy, and can be used for research and routine production.


Pharmacologic management of acutely agitated pediatric patients.
Acute agitation is a state of behavioral dyscontrol that requires intervention. Medications available in rapid delivery formats are frequently administered to treat acute agitation, either as a chemical restraint or on a voluntary basis. Prior to initiating treatment, the etiology of agitation must be evaluated. In choosing a medication, general pharmacologic principles should be followed. Medication should be selected based on the underlying cause in conjunction with weighing the risks, benefits, and side effects of medications. There are three classes of medications administered to children and adolescents to treat agitation: antihistamines, benzodiazepines, and antipsychotics. The most concerning short-term side effects of antipsychotics are their adverse neurologic effects, neuroleptic malignant syndrome, and prolonged corrected QT interval. Compared with typical antipsychotics, atypical antipsychotics have a more favorable short-term side effect profile.


Unlocking bone for proteomic analysis and FISH.
Bone tissue is critically lagging behind soft tissues and biofluids in our effort to advance precision medicine. The main challenges have been accessibility and the requirement for deleterious decalcification processes that impact the fidelity of diagnostic histomorphology and hinder downstream analyses such as fluorescence in-situ hybridization (FISH). We have developed an alternative fixation chemistry that simultaneously fixes and decalcifies bone tissue. We compared tissue morphology, immunohistochemistry (IHC), cell signal phosphoprotein analysis, and FISH in 50 patient matched primary bone cancer cases that were either formalin fixed and decalcified, or theralin fixed with and without decalcification. Use of theralin improved tissue histomorphology, whereas overall IHC was comparable to formalin fixed, decalcified samples. Theralin-fixed samples showed a significant increase in protein and DNA extractability, supporting technologies such as laser-capture microdissection and reverse phase protein microarrays. Formalin-fixed bone samples suffered from a fixation artifact where protein quantification of β-actin directly correlated with fixation time. Theralin-fixed samples were not affected by this artifact. Moreover, theralin fixation enabled standard FISH staining in bone cancer samples, whereas no FISH staining was observed in formalin-fixed samples. We conclude that the use of theralin fixation unlocks the molecular archive within bone tissue allowing bone to enter the standard tissue analysis pipeline. This will have significant implications for bone cancer patients, in whom personalized medicine has yet to be implemented.


Three-Center M-H-B Bonds Are Strong Field Interactions. Synthesis and Characterization of M(CH2NMe2BH3)3 Complexes of Titanium, Chromium, and Cobalt.
We describe new compounds of stoichiometry M(CH2NMe2BH3)3 (M = Ti, Cr, and Co), each of which contains three chelating boranatodimethylaminomethyl (BDAM) ligands. In all three compounds, the BDAM anion, which is isoelectronic and isostructural with the neopentyl group, is bound to the metal center at one end by a metal-carbon σ bond and at the other by one three-center M-H-B interaction. The crystal structures show that the d1 titanium(III) compound is trigonal prismatic (or eight-coordinate, if two longer-ranged M···H interactions with the BH3 groups are included), whereas the d3 chromium(III) compound and the d6 cobalt(III) compounds are both fac-octahedral. The Cr and Co compounds exhibit two rapid dynamic processes in solution: exchange between the Δ and Λ enantiomers and exchange of the terminal and bridging hydrogen atoms on boron. For the Co complex, the barrier for Δ/Λ exchange (ΔG⧧298 = 10.1 kcal mol-1) is significantly smaller than those seen in other octahedral cobalt(III) compounds; DFT calculations suggest that Bailar twist and dissociative pathways for Δ/Λ exchange are both possible mechanisms. The UV-vis absorption spectra of the cobalt(III) and chromium(III) species show that the ligand field splittings Δo caused by the M-H-B interactions are unexpectedly large, thus placing them high on the spectrochemical series (near ammonia and alkyl groups); their nephelauxetic effect is also large. The DFT calculations suggest that these properties of M-H-B interactions are in part a consequence of their three-center nature, which delocalizes electron density away from the metal center and reduces electron-electron repulsions.


[Ocular lesions due to plant foreign bodies].
The results of a survey done during the period 1988-1993, regarding the cases of ocular lesions due to vegetal foreign bodies, are presented in 51.1% of the 156 cases involved patients over 50-years-old, especially from country-side, originating in accidents during agricultural labour (79.2%). The main clinical forms of the ocular lesions as well as the nature of the vegetal foreign bodies are described. Some rare clinical aspects, involving toxic-allergic mechanisms of the ocular lesions are also mentioned. Three observations of corneal ulcerations due to vegetal foreign bodies are presented, the therapeutical methods and the evolution of visual acuity during hospitalization are also described.


Effect of somatostatin on pentagastrin-stimulated gastric acid secretion and gastric antral motility in dogs with gastric fistula.
The purpose of the present study was to evaluate the effect of somatostatin on gastric acid secretion and gastric antral motility in conscious dogs with gastric fistula. Infusion of pentagastrin induced motility with a digestive pattern. Somatostatin inhibited dose-dependently the stimulated acid secretion, whereas the effect on antral motility was more complex, acting especially on the amplitude of the contractions. The effects of somatostatin were not altered by using alpha- and beta-adrenergic, dopaminergic, and serotonergic blocking drugs. The dose-response kinetics with seven doses of pentagastrin with and without somatostatin showed inhibition of a competitive type for gastric acid secretion and of a non-competitive type for antral motility with regard to amplitude.


Acute nonlymphocytic leukemia: the first 48 hours.
The initial care of patients with acute nonlymphocytic leukemia can be lifesaving. Such patients are most often treated at tertiary care centers where resident physicians, working under the supervision of a subspecialist, are responsible for the diagnosis and initial treatment. During the first 48 hours, the house officer must recognize and understand the management of perilous complications such as hyperleukocytosis, hemorrhage, and infection. Specific lifesaving measures will grant the patient and his physicians sufficient time to reach a decision regarding the initiation of curative induction chemotherapy.


[Complications of intrathecal baclofen therapy].
To analyze complications of intrathecal baclofen therapy and identify high-risk groups. We implanted 52 pumps to spastic patients for chronic intrathecal baclofen infusion. Two groups of patients were distinguished: 23 patients with spinal spasticity (group 1) and 29 patients with cerebral spasticity (group 2). The mean patient age was 37.2±14.6 years in group 1 and 17.3±10.3 years in group 2. Surgery was performed according to a standard procedure. A Medstream (Codman) pump was implanted in 10 cases, and a Synchromed II (Medtronic) pump was implanted in the remaining 42 cases. Complications developed in 12 (23%) patients. We divided complications into 3 groups: baclofen underdose, baclofen overdose, and others. Insufficiency of intrathecal therapy was observed in 7 cases, which was caused by catheter migration (5 cases) and pump dysfunction (2 cases). In one case, baclofen overdose was observed after air travel. Other complications included 4 cases of persistent peri-implant seroma and infectious complications. Groups with a high risk of complications were identified based on an analysis of the results. Patients with severe dystonia of the trunk muscles have an increased risk of spinal catheter migration. Pronounced communicating hydrocephalus is associated with the risk of cerebrospinal fluid leak through a catheter shaft channel. Weakness of the axial musculature can lead to progression of scoliotic deformity. In some cases, chronic intrathecal baclofen therapy can be accompanied by various complications. This technique should be carefully used in patients from high-risk groups.


Evidence accumulation is biased by motivation: A computational account.
To make good judgments people gather information. An important problem an agent needs to solve is when to continue sampling data and when to stop gathering evidence. We examine whether and how the desire to hold a certain belief influences the amount of information participants require to form that belief. Participants completed a sequential sampling task in which they were incentivized to accurately judge whether they were in a desirable state, which was associated with greater rewards than losses, or an undesirable state, which was associated with greater losses than rewards. While one state was better than the other, participants had no control over which they were in, and to maximize rewards they had to maximize accuracy. Results show that participants' judgments were biased towards believing they were in the desirable state. They required a smaller proportion of supporting evidence to reach that conclusion and ceased gathering samples earlier when reaching the desirable conclusion. The findings were replicated in an additional sample of participants. To examine how this behavior was generated we modeled the data using a drift-diffusion model. This enabled us to assess two potential mechanisms which could be underlying the behavior: (i) a valence-dependent response bias and/or (ii) a valence-dependent process bias. We found that a valence-dependent model, with both a response bias and a process bias, fit the data better than a range of other alternatives, including valence-independent models and models with only a response or process bias. Moreover, the valence-dependent model provided better out-of-sample prediction accuracy than the valence-independent model. Our results provide an account for how the motivation to hold a certain belief decreases the need for supporting evidence. The findings also highlight the advantage of incorporating valence into evidence accumulation models to better explain and predict behavior.