Rotavirus incidence and genotype distribution before and after national rotavirus vaccine introduction in Belgium.
Rotarix™ was introduced into the Belgian market in 2006 and RotaTeq™ in 2007, quickly reaching more than 85% vaccine coverage of all newborns in Belgium. The incidence of rotavirus gastroenteritis has been monitored in the Gasthuisberg University Hospital (GUH), Belgium since 1986, and since 1999 the genotypes of circulating rotavirus strains have been determined. The average percentage of rotavirus positive cases out of all hospitalized gastro-enteritis cases tested (>95% of these cases are younger than 5 years old) at the GUH between 1986 and 2006 was 19.0%. This percentage dropped to 12.4%, 9.6% and 6.4% in the three seasons post vaccine introduction (2006-2009), which is a decline of 34.7%, 49.4% and 66.3% respectively. In addition the rotavirus season was found to be shortened and delayed. The prevalence of the G2 genotype sharply increased in the 2006-2007 rotavirus season compared to the previous seasons and remained high (30-40%) in the 2007-2008 and 2008-2009 seasons. Rotavirus vaccines have strongly reduced the number of children hospitalized due to a rotavirus infection at the GUH; it is however unclear if the predominance of G2 genotypes is related to the vaccine introduction, or if this is attributable to normal genotype fluctuations. Continued surveillance will be pivotal to answer this question in the future.


Inhibition of class D beta-lactamases by acyl phosphates and phosphonates.
The susceptibility of typical class D beta-lactamases to inhibition by acyl phosph(on)ates has been determined. To a large degree, these class D enzymes behaved very similarly to the class A TEM beta-lactamase towards these reagents. Dibenzoyl phosphate stood out in both cases as a lead compound towards a new class of effective inhibitors.


[The effect of the electrical stimulation of the superior colliculli on focal epileptic activity in the cerebral cortex ].
Acute experiments in rats showed that SC electrical stimulation (ES) (100 Hz, 5 V, 0.25 ms) resulted in suppression of the epileptic activity in contralateral strychnine-induced (0.1%; 1.0%) focus and shortening of the focus existence time. After electrocoagulation of SC ES-zone the EpA in the focus was restored. ES of SC ipsilateral to strychnine-induced (0.1%) focus caused an increase in the spike frequencies but significant part of the antiepileptic system.


Gene replacement therapy for non-small cell lung cancer: a review.
Current therapy such as radiation and chemotherapy controls less than 50% of lung cancers, summoning the development of novel therapeutic strategies that can directly target the underlying mechanisms of tumorigenesis. The clinical trials summarized in this article clearly demonstrate that contrary to initial predictions that gene therapy would not be suitable for cancer, gene replacement therapy is a viable potential addition to the arsenal for cancer. Gene expression has been documented and occurs even in the presence of an antiadenovirus immune response. Clinical trials have demonstrated that direct intratumor injection can cause tumor regression or prolonged stabilization of local disease, and the low toxicity associated with gene transfer indicates that tumor suppressor gene replacement can be readily combined with existing and future treatments. Initial concerns that the wide diversity of genetic lesions in cancer cells would prevent the application of gene therapy to cancer appear unfounded; on the contrary, correction of a single genetic lesion has resulted in significant tumor regression. Studies combining transfer of tumor suppressor genes with conventional DNA-damaging treatments indicate that correction of a defect in apoptosis induction can restore sensitivity to radiation and chemotherapy in some resistant tumors, and indications that sensitivity to killing might be enhanced in already sensitive tumors may eventually lead to reduced toxicity from chemotherapy and radiation therapy. The most recent data from the laboratory demonstrating damage to tumor suppressor genes in normal tissue and premalignant lesions even suggest that these genes may someday be useful in early intervention, diagnosis, and even prevention of cancer. Despite the obvious promise evident in the results of these studies, however, it is critical to recognize that there are still gaps in knowledge and technology to address. At the current rate of biotechnology development, it is only a matter of time until technical limitations that currently prevent the widespread application of gene therapy to cancer are overcome by development of more efficient vectors, discovery of novel genes, and development of combined modality approaches.


Effect of prostaglandin E2 on masculine sexual behaviour in the rat.
Intracerebral infusion of prostaglandin E2 (PGE2) facilitated copulatory behaviour of long-term castrated rats. Castrated rats were given daily systemic injections of testosterone propionate (50 microgram) or oil vehicle, and then 30 min before behavioural testing they received an intrahypothalamic infusion of either PGE2 or saline. Rats receiving PGE2 in addition to systemic testosterone showed more copulatory behaviour than those receiving PGE2 or testosterone alone.


Differential expression of interleukins IL-13 and IL-15 in normal ovarian tissue and ovarian carcinomas.
To determine the temporal and spatial expression of interleukins (IL)-13 and IL-15 in ovarian carcinoma compared to normal ovarian tissue. Quantitative RT-PCR, ELISA and immunohistochemistry. Q-RT-PCR, ELISA and immunohistochemical analysis indicates that IL-13 and IL-15 mRNA and protein are expressed in normal ovary at various phases of the menstrual cycle with immunoreactive proteins detected in granulosa/theca and luteal cells and to a lesser extent in stromal cells and surface epithelial cells. Compared to normal ovary, ovarian carcinoma expresses elevated levels of IL-13 and IL-15 mRNA, with higher IL-13 expression in primary vs. metastatic tumors. IL-13 and IL-15 protein expression was also higher in the tumor tissues compared to ascites. In normal ovary, ovarian tumors and ascites, the ratio of IL-13/IL-15 favored IL-13. Immunoreactive IL-13 and IL-15 proteins were localized primarily in the tumor cells and infiltrated inflammatory cells with increased intensity with disease stage. Normal ovary and ovarian tumors express IL-13 and IL-15 and pattern of their expression in carcinomas suggests that these cytokines may function in various ovarian cellular activities including inflammatory/immune responses that are integrated cellular events taking place in normal ovary and ovarian tumors.


Dipstick Spot urine pH does not accurately represent 24 hour urine PH measured by an electrode.
To determine whether spot urine pH measured by dipstick is an accurate representation of 24 hours urine pH measured by an electrode. We retrospectively reviewed urine pH results of patients who presented to the urology stone clinic. For each patient we recorded the most recente pH result measured by dipstick from a spot urine sample that preceded the result of a 24-hour urine pH measured by the use of a pH electrode. Patients were excluded if there was a change in medications or dietary recommendations or if the two samples were more than 4 months apart. A difference of more than 0.5 pH was considered na inaccurate result. A total 600 patients were retrospectively reviewed for the pH results. The mean difference in pH between spot urine value and the 24 hours collection values was 0.52±0.45 pH. Higher pH was associated with lower accuracy (p<0.001). The accuracy of spot urine samples to predict 24-hour pH values of <5.5 was 68.9%, 68.2% for 5.5 to 6.5 and 35% for >6.5. Samples taken more than 75 days apart had only 49% the accuracy of more recent samples (p<0.002). The overall accuracy is lower than 80% (p<0.001). Influence of diurnal variation was not significant (p=0.588). Spot urine pH by dipstick is not an accurate method for evaluation of the patients with urolithiasis. Patients with alkaline urine are more prone to error with reliance on spot urine pH.


A method for increasing the surface details of resin embedded viruses using Congo/Crimean haemorrhagic fever virus as a model.
The surface details of resin embedded viruses can be greatly enhanced by the use of uranyl acetate block staining. The virions are embedded in agar immediately after fixation and block stained with 3% uranyl acetate in methanol during dehydration. This technique allows those particles outside their host cells to show clearly the spikes normally seen only by the separate use of negative staining.


WY-14643 attenuates lipid deposition via activation of the PPARα/CPT1A axis by targeting Gly335 to inhibit cell proliferation and migration in ccRCC.
Histologically, cytoplasmic deposits of lipids and glycogen are common in clear cell renal cell carcinoma (ccRCC). Owing to the significance of lipid deposition in ccRCC, numerous trials targeting lipid metabolism have shown certain therapeutic potential. The agonism of peroxisome proliferator-activated receptor-α (PPARα) via ligands, including WY-14,643, has been considered a promising intervention for cancers. First, the effects of WY-14,643 on malignant behaviors were investigated in ccRCC in vitro. After RNA sequencing, the changes in lipid metabolism, especially neutral lipids and glycerol, were further evaluated. Finally, the underlying mechanisms were revealed. Phenotypically, the proliferation and migration of ccRCC cells treated with WY-14,643 were significantly inhibited in vitro. A theoretical functional mechanism was proposed in ccRCC: WY-14,643 mediates lipid consumption by recognizing carnitine palmitoyltransferase 1 A (CPT1A). Activation of PPARα using WY-14,643 reduces lipid deposition by increasing the CPT1A level, which also suppresses the NF-κB signaling pathway. Spatially, WY-14,643 binds and activates PPARα by targeting Gly335. Overall, WY-14,643 suppresses the biological behaviors of ccRCC in terms of cell proliferation, migration, and cell cycle arrest. Furthermore, its anticancer properties are mediated by the inhibition of lipid accumulation, at least in part, through the PPARα/CPT1A axis by targeting Gly335, as part of the process, NF-κB signaling is also suppressed. Pharmacological activation of PPARα might offer a new treatment option for ccRCC.


The Effects of Metal Exposures on Charlson Comorbidity Index Using Zero-Inflated Negative Binomial Regression Model: NHANES 2011-2016.
With the rising incidence of chronic diseases, and the increase of aging population has led to multimorbidity a serious public health problem. The aim of this study was to explore the association between metal exposures and Charlson comorbidity index (CCI), which will provide valuable information for improving quality of life and reducing mortality. The study sample consists of three continuous cycles (2011-2016) of the National Health and Nutrition Examination Survey (NHANES), and 4901 eligible subjects were included in the study. Zero-inflated negative binomial (ZINB) model was utilized to investigate the effects in metal exposures on CCI, which includes spot urine (arsenic, mercury, and cadmium), whole blood (manganese, selenium, and lead), and serum (copper and zinc). In count part (CCI ≥ 0), holding other variables constant, the expected change in CCI for a one-unit increase in blood selenium is 0.997 (RR = 0.997, p = 0.017). In logit part (CCI = 0), the log odds of having CCI equals zero would increase by 0.659, 1.073, and 0.963 for every additional urinary cadmium (OR = 0.659, p = 0.007), blood lead (OR = 1.073, p = 0.023), blood manganese (OR = 0.963, p = 0.025), respectively. Our findings indicated that cadmium and manganese were likely to increase mortality. Inversely, selenium and lead might be positive on people's health. The findings may be extremely essential for preventing diseases and improving life quality.


Genetic variation, pseudocryptic diversity, and phylogeny of Erpobdella (Annelida: Hirudinida: Erpobdelliformes), with emphasis on Canadian species.
Leeches of the family Erpobdellidae are important members of benthic freshwater environments, where they are voracious predators of other invertebrates and an important source of nutrition for several species of vertebrates. Beset by a lack of reliable diagnostic morphological characters and destructive identification processes, molecular approaches have, in recent years, been employed to illuminate the relationships within this family, and DNA barcoding has been employed for identification purposes. However, an understanding of the levels of genetic variation across the geographic distributions of members of the genus is still lacking. Herein, we sequence the mitochondrial COI locus for 249 newly collected North American individuals, representing 5 species, as well as mitochondrial 12S rDNA, nuclear 18S rDNA, and nuclear 28S rDNA for a select subset of these. Our COI dataset was leveraged to detect potential cryptic species, and to calculate genetic distances as a proxy for the degree of gene flow between populations. Augmented by numerous sequences from GenBank, the multilocus dataset was used to reconstruct a phylogenetic hypothesis for worldwide members of the genus. Beyond corroborating previous overarching phylogenetic frameworks, our results show that an undescribed species that is morphologically and genetically similar to Erpobdella punctata exists in sympatry with this species - the new species has likely been overlooked in previous studies due to its morphological similarity with Erpobdella punctata. Erpobdella bucera is reported from Canada for the first time; and Erpobdella microstoma is newly reported from Saskatchewan and placed in a phylogeny for the first time. Finally, we find evidence for genetic structure in both E. cf. punctata and Erpobdella obscura that is correlated with major river drainage basin boundaries in North America.


Management of acidosis during lung-protective ventilation in acute respiratory distress syndrome.
In ARDS, when acidosis complicates LPV, the goal of alkali therapy is to maintain arterial pH at a safe level (> or = 7.20). A pure respiratory acidosis generally does not require alkali therapy. If the Pplat is greater than 30 cm H2O, and the respiratory rate equals the upper limit (35-40 breaths/minute), then V(E) is slowly titrated down by approximately 1 L/hour, so that PaCO2 increases by 10 mm Hg/hour or less. Alkali therapy is indicated for either a metabolic acidosis or a mixed acidosis. The choice of buffer is based on the type of acidosis, cardiorespiratory status, and lung mechanics. Slow infusions of NaHCO3 can be used to treat non-anion gap metabolic acidosis and some forms of increased anion gap acidosis. Using NaHCO3 to treat type A (hypoxia-related) lactic acidosis can be hazardous, particularly under conditions of hypoxemia, inadequate circulation, and limited alveolar ventilation. Under these circumstances, THAM is the preferable buffer because it does not increase PaCO2 and is excreted by the kidneys. When renal failure is present, CRRT is indicated to manage acidosis. When ARDS is complicated by traumatic or hemorrhagic shock, overresuscitation with Cl(-)-rich solutions should be avoided to prevent metabolic acidosis.


Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumours by enzymes concentrated in human liver and cancer tissue.
Capecitabine (N4-pentyloxycarbonyl-5'-deoxy-5-fluorocytidine) is a novel oral fluoropyrimidine carbamate, which is converted to 5-fluorouracil (5-FU) selectively in tumours through a cascade of three enzymes. The present study investigated tissue localisation of the three enzymes in humans, which was helpful for us to design the compound. Carboxylesterase was almost exclusively located in the liver and hepatoma, but not in other tumours and normal tissue adjacent to the tumours. Cytidine (Cyd) deaminase was located in high concentrations in the liver and various types of solid tumours. Finally, thymidine phosphorylase (dThdPase) was also more concentrated in various types of tumour tissues than in normal tissues. These unique tissue localisation patterns enabled us to design capecitabine. Oral capecitabine would pass intact through the intestinal tract, but would be converted first by carboxylesterase to 5'-deoxy-5-fluorocytidine (5'-dFCyd) in the liver, then by Cyd deaminase to 5'-deoxy-5-fluorouridine (5'-dFUrd) in the liver and tumour tissues and finally by dThdPase to 5-FU in tumours. In cultures of human cancer cell lines, the highest level of cytotoxicity was shown by 5-FU itself, followed by 5'-dFUrd. Capecitabine and 5'-dFCyd had weak cytotoxic activity only at high concentrations. The cytotoxicity of the intermediate metabolites 5'-dFCyd and 5'-dFCyd was suppressed by inhibitors of Cyd deaminase and dThdPase, respectively, indicating that these metabolites become effective only after their conversion to 5-FU. Capecitabine, which is finally converted to 5-FU by dThdPase in tumours, should be much safer and more effective than 5-FU, and this was indeed the case in the HCT116 human colon cancer and the MX-1 breast cancer xenograft models.


High-Grade Sarcoma Arising in Association With an Intraosseous Lipoma: A Case Report.
A 78-year-old man was followed for an incidentally found, asymptomatic lesion in his right proximal femur that was unchanged radiographically for 11 years. He developed pain and was believed to have experienced a stress fracture through the lesion. The lesion was biopsied, showing a high-grade pleomorphic sarcoma with an underlying senescent intraosseous lipoma. He was ultimately treated with wide excision and reconstruction of the proximal femur. This case highlights the importance of obtaining a tissue diagnosis for lesions that become symptomatic.


What really happened? A validation study of rape survivors' help-seeking experiences with the legal and medical systems.
Much of what is known about rape survivors' experiences with the legal and medical systems has come from victims' accounts; rarely have researchers collected "the other side of the story" to find out what system personnel say did or did not happen in these interactions. In the current study, rape survivors who sought emergency medical care were interviewed before their hospital discharge about what services they received and how they were treated by social system personnel. Corresponding accounts were then collected from doctors, nurses, and police officers. There was significant interrater reliability between the survivors and legal and medical system personnel regarding what services were or were not provided ("service delivery") and if system personnel engaged in "secondary victimization" behaviors (i.e., statements/actions that could be distressing to victims). However, police officers and doctors significantly underestimated the impact they were having on survivors. Victims reported significantly more post-system-contact distress than service providers thought they were experiencing.


Competitive release in microhabitat use among coexisting desert rodents: a natural experiment.
Competitive release among desert rodents on sand dunes of differing species richness was examined in the Great Basin and Mohave Deserts, USA. Expansions in microhabitat use were exhibited by the kangaroo rats Dipodomys ordii and D. merriami (granivorous heteromyid rodents, weighing 49 and 42 g, respectively) as the number of coexisting heteromyid species decreased geographically. Perognathus longimembris, the only common small heteromyid species (7 g) exhibited no competitive release. This may be due either to the absence of competitive interactions that affect the use of space by P. longimembris or to an unacceptable increase in risk of predation that precludes the use of more open microhabitats even in the absence of kangaroo rats. The breadth of microhabitat use of an omnivorous cricetid, Peromyscus maniculatus, decreased as the density of Perognathus longimembris increased, and increased as the density of conspecifics increased. The evidence for competitive release in Dipodomys and not in Perognathus is consistent with the hypothesis that species in the same guild and of similar size compete more intensely than species of disparate size.


Defining Types and Determining Risk Factors for Vascular Surgery Readmissions.
Vascular surgery patients typically have numerous comorbidities, which puts them at higher risk for postoperative readmissions. This study aims to investigate the risk factors for and appropriately categorize the various types of vascular surgery readmissions. Nine hundred seventy-two patients were retrospectively reviewed. Readmissions were classified into 3 separate groups: readmissions that occurred between 0 and 30 days (30-day readmissions), 31-90 days (3-month readmissions), and 91-365 days (1-year readmissions). Each readmission was then assigned to 1 of the 4 categories based on whether they were related to the index procedure and whether they were planned. Univariate tests were performed for demographic variables based on their type of readmission, and logistic regressions were then performed to identify predictors of each unplanned, related readmissions. The overall 30-day readmission rate was 21.9% (n = 213). The unplanned, related readmission cohort (n = 83) had the highest readmission rate of 8.5%. The related, planned readmission rate was 5.9% (n = 58), while the unrelated, unplanned readmission rate was 5.6% (n = 55). In contrast, the overall 1-year readmission rate was 40.0% (n = 389), with the largest category being unplanned, unrelated readmissions at 19.7% (n = 191). The unplanned, related readmission rate was 8.7% (n = 85), whereas the planned, related readmission rate was 5.7% (n = 55). Compared with other types of readmissions, unplanned, related readmissions tended to affect patients who were younger, had poor glycemic control, and had higher body mass indexes (BMIs). Multivariate predictors of unplanned, related readmissions were poor glycemic control at 3 months (odds ratio [OR]: 2.16, P = 0.03), and BMI at 30 days (OR: 1.06, P = 0.04) and 1 year (OR: 1.05, P = 0.04). Readmissions have varying risk factors depending on their category; targeting glycemic control and obesity may reduce unplanned, related readmissions.


A Copper10-Paclitaxel crystal; a medicinally active drug delivery platform.
Paclitaxel is a well-known cancer drug that functions as a mitotic inhibitor. This work focuses on a copper based crystal that encapsulates the pharmaceutical agent and serves as a drug delivery agent. A Copper10-Pacitaxil1 chloride (CU10PAC1) complex is synthesized and tested against the National Cancer Institute's sixty cell line panel. The 10:1 ratio results in a crystal that was examined by Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spec (MALDI-TOF-MS), Scanning Electron Microscopy (SEM) and Proton (1H) and Carbon (13C) Nuclear Magnetic Resonance (NMR). The potential attributes of a copper based crystal as an in vivo drug carrier for Paclitaxel are discussed.


Family history of anxiety and mood disorders in anorexia nervosa: review of the literature.
To provide a critical review of the research on mood and anxiety disorders in relatives of individuals with anorexia nervosa (AN). In the first section, we explore methodological issues with these studies. In the second section, we present results. A Medline search identified studies published on family history of mood and anxiety disorders in AN, and was complemented by a manual search. Only studies from 1980 to 2006 using strict diagnostic criteria for the disorders were included [Feighner and Halmi criteria for AN, Reasearch Diagnostic Criteria (RDC), Diagnostic and Statistical Manual of Mental Disorders - Third Edition - Revised (DSM-III-R) or DSM - Fourth Edition (DSM-IV) for anorexia and other disorders]. A review of the research methods used in the studies revealed a number of methodological problems. Therefore, we provide only a description of the prevalence of mood and anxiety disorders in relatives of individuals with AN. In the light of the methodological issues uncovered, the value of the results of these studies and their implications for further study are considered.


EnCOUNTer: a parsing tool to uncover the mature N-terminus of organelle-targeted proteins in complex samples.
Characterization of mature protein N-termini by large scale proteomics is challenging. This is especially true for proteins undergoing cleavage of transit peptides when they are targeted to specific organelles, such as mitochondria or chloroplast. Protein neo-N-termini can be located up to 100-150 amino acids downstream from the initiator methionine and are not easily predictable. Although some bioinformatics tools are available, they usually require extensive manual validation to identify the exact N-terminal position. The situation becomes even more complex when post-translational modifications take place at the neo-N-terminus. Although N-terminal acetylation occurs mostly in the cytosol, it is also observed in some organelles such as chloroplast. To date, no bioinformatics tool is available to define mature protein starting positions, the associated N-terminus acetylation status and/or yield for each proteoform. In this context, we have developed the EnCOUNTer tool (i) to score all characterized peptides using discriminating parameters to identify bona fide mature protein N-termini and (ii) to determine the N-terminus acetylation yield of the most reliable ones. Based on large scale proteomics analyses using the SILProNAQ methodology, tandem mass spectrometry favoured the characterization of thousands of peptides. Data processing using the EnCOUNTer tool provided an efficient and rapid way to extract the most reliable mature protein N-termini. Selected peptides were subjected to N-terminus acetylation yield determination. In an A. thaliana cell lysate, 1232 distinct proteotypic N-termini were characterized of which 648 were located at the predicted protein N-terminus (position 1/2) and 584 were located further downstream (starting at position > 2). A large number of these N-termini were associated with various well-defined maturation processes occurring on organelle-targeted proteins (mitochondria, chloroplast and peroxisome), secreted proteins or membrane-targeted proteins. It was also possible to highlight some protein alternative starts, splicing variants or erroneous protein sequence predictions. The EnCOUNTer tool provides a unique way to extract accurately the most relevant mature proteins N-terminal peptides from large scale experimental datasets. Such data processing allows the identification of the exact N-terminus position and the associated acetylation yield.


Fibrofolliculoma: solitary and multiple types.
Multiple skin tumors generally show autosomal dominant inheritance and are sometimes associated with other cutaneous and internal lesions. Solitary growths are typically nonhereditary and unassociated with other abnormalities. We found only two previous reports of solitary fibrofolliculoma and only one of multiple fibrofolliculomas without associated lesions; a few publications describe multiple fibrofolliculomas in patients with perifollicular fibromas, trichodiscomas, acrochordons, and connective tissue nevus. We studied five new cases of solitary nonhereditary fibrofolliculomas and one of multiple familial fibrofolliculomas without associated lesions. Clinically, fibrofolliculomas were typically small growths with a central dilated follicle containing horny material. Histologically, there was characteristically a hyperplastic follicular infundibulum with a central keratinous plug, and anastomosing strands of basaloid cells branching into an angiofibromatous stroma. Fibrofolliculoma is thus another skin tumor in which patients with multiple growths showing autosomal dominant inheritance sometimes have associated abnormalities, while solitary lesions with identical clinical and microscopic features are relatively trivial and nonhereditary.


Sonographic diagnosis and prognosis of fetal arachnoid cysts.
To explore the clinical significance of sonographic (US) diagnosis of fetal arachnoid cysts and to evaluate their prognosis. Sixty fetuses deemed to have arachnoid cysts by prenatal US were included in this study. Data from serial US, prenatal and/or postnatal MRI, or post-mortem examinations were retrospectively analyzed. For live births, the developmental quotient scores were determined using the Gesell Developmental Scale. Thirty fetuses were diagnosed during the second trimester and another 30 fetuses were diagnosed in the third trimester. Fifty-one lesions were located in the supratentorial compartment, and 9 were located in the posterior fossa. Twenty-four lesions were isolated, and the remaining lesions were associated with intracranial and/or extra central nervous system malformations. The evolution of the cysts included progression, stability, or spontaneous resolution. The outcomes included induced abortion, intrauterine death, live birth with either normal neurodevelopment or mental retardation, and infant mortality. Two cases were lost to follow-up. The accuracy of prenatal US diagnosis was 86.2% (50/58). Prenatal US is the modality of choice for the diagnosis of fetal arachnoid cysts. Serial US examinations are critical to monitor the lesions. Moreover, prenatal MRI is a valuable complementary tool. For live births, the prognosis appears to be good.


Estimation of sediment accumulation rates using naturally occuring ²¹⁰Pb models in Gülbahçe Bay, Aegean Sea, Turkey.
The sediment chronology was determined using Lead-210 (²¹⁰Pb) dating method in Gülbahçe Bay. Sediment cores were obtained using gravity core sampler from hydrothermal area and also from reference point and surfical distribution of Polonium-210 (²¹⁰Pb) was investigated in the study area. The average of surfical concentration of ²¹⁰Po was found as 175.25 ± 3.80 Bq kg⁻¹ in the hydrothermal area which was higher than the reference point value of 133.20 ± 3.30 Bq kg⁻¹. Sedimentation rates in Core reference point (RN) displayed an increase till the year 1942 and a decrease afterwards, sedimentation rates in any core from hydrothermal area have not exhibited any continuous increase or decrease. The ²¹⁰Pb fluxes measured from core inventories are close to each other. Average enrichment factors for Cu, Cd, Sr, Zn, Cr vary between 20.35 and 12.18 indicating that the sediments have been contaminated with these metals in the reference point. Maximum enrichment factor values for Cr, Cu, Zn, Ba, Sr, Ni, Co vary between 22.91 and 11.42, implying that the sediments in hydrothermal area have been contaminated with these metals.


Validation of a procedure for exogenous isotopic labeling of lipoprotein triglyceride with radioactive triolein.
A procedure has been developed for the exogenous isotopic labeling of triglyceride-rich lipoproteins (chylomicrons and very low density lipoproteins) using high specific activity radioactive triglyceride in the presence of aqueous dimethyl sulfoxide. The labeled product lipoproteins showed unchanged chemical and physical properties. When the particles had also been labeled biologically by incorporation of unesterified fatty acids into the triglycerides of lipoproteins secreted by liver or intestine, both endogenous and exogenous labels were removed at the same rates in the isolated perfused heart and liver or in intact or functionally hepatectomized rats. These experiments additonally indicated that the triglyceride fatty acid composition of chylomicrons and very low density lipoproteins was unchanged during triglyceride depletion in the peripheral tissues. Using such labeled lipoproteins it has been shown that uptake of remnant lipoprotein cholesteryl ester and triglyceride by the liver is simultaneous. The labeling procedure described should prove suitable for kinetic studies of the disposition of the various lipoprotein non-polar ('core') lipids.


Eccrine porocarcinoma of the upper eyelid.
A 75-year-old Caucasian man presented with foreign-body-type irritation of the left eye. Physical examination revealed a 12 x 10-mm nodule in his left upper eyelid, which reportedly had been present unchanged for more than 40 years. No other ophthalmological abnormalities were present. Incisional biopsy of the lesion revealed a malignant tumour that was thought to possibly represent a sebaceous carcinoma. However, a subsequent wide surgical excision showed that the tumour was an eccrine porocarcinoma, a rare sweat gland adenocarcinoma arising from the acrosyringium.


Chemical shifts in amino acids, peptides, and proteins: from quantum chemistry to drug design.
This chapter discusses recent progress in the investigation and use of (13)C, (15)N, and (19)F nuclear magnetic resonance (NMR) chemical shifts and chemical shift tensors in proteins and model systems primarily using quantum chemical (ab initio Hartree-Fock and density functional theory) techniques. Correlations between spectra and structure are made and the techniques applied to other spectroscopic and electrostatic properties as well, including hydrogen bonding, ligand binding to heme proteins, J-couplings, electric field gradients, and atoms-in-molecules theory, together with a brief review of the use of NMR chemical shifts in drug design.


Endothelin-1 increase in aqueous humour caused by frequency-doubled Nd:YAG laser trabeculoplasty in rabbits.
To study the effect of Nd:YAG laser trabeculoplasty (LT) on endothelin-1 (ET-1) concentration of aqueous humour and intraocular pressure (IOP) in rabbits. One eye of each of 18 pigmented rabbits was subjected to 360 degrees LT with a frequency-doubled Nd:YAG laser (532 nm), and IOP was measured with a Tono-Pen tonometer before treatment. Post-LT IOP measurements followed by aqueous humour aspiration were performed under general anaesthesia at 3 and 12 h and 1, 3 and 7 days after the treatment. The concentration of ET-1 in aqueous humour was measured by means of a radioimmunoassay. In the eyes that had undergone LT, the concentrations of ET-1 in the aqueous humour were significantly increased at 3, 12 and 24 h after the treatment compared with the contralateral eyes. ET-1 concentrations at 3 and 7 days after LT, however, did not differ significantly from the corresponding contralateral control values. IOP increased following the treatment at 3 and 12 h. IOP values were significantly lower in the treated eyes at 1, 3 and 7 days after the treatment than in the control eyes. The results show that LT in rabbits was followed by an immediate and short-term increase in aqueous humour ET-1 that might be caused by leakage from uveal tissue. This may be responsible for the release of prostaglandins causing the IOP increase and inflammatory complications of LT.


Transparent Golgi impregnations: a way to examine both details of cellular processes and components of the nerve cell body.
A method is described by which the precipitate that normally fills impregnated cells in Golgi preparations is confined to a thin and transparent scattering of fine particles that defines the somata and cellular processes. The coating is stable enough to withstand counterstaining and thus makes possible direct evaluation of structural features not only of cellular processes but also of cytoplasmic components.


Matching of normally oriented and mirrored words by good and poor readers.
10 good and 10 poor Grade 6 readers judged tachistoscopically presented word pairs to be "same" or "different" when the words making up the pairs were both normally oriented, both mirrored, or one was oriented and the other was mirrored. Good readers made fewer errors than poor readers on normally oriented "same" pairs but showed no advantage on other configurations. Poor readers were more accurate in detecting mismatches than good readers. These results were discussed in terms of the mechanism that may have been implicated.


Professionals' views on the "optimal time" for people living with dementia to move to a care home.
The decision about the best time for a person living with dementia to move to a care home involves the individual and others, particularly family. However, little is known about care professionals' views on the best time to move, particularly those with decision-making authority. This study investigated social workers' and care home managers' views on whether there is an "optimal time" for a move. A qualitative, phenomenological approach was employed, using semi-structured interviews with 20 social workers and 20 care home managers in England; all with experience of advising people living with dementia about a care home move and making decisions about funding or acceptance. Interviews were audio-recorded, transcribed, and analyzed thematically. Four overarching themes emerged from the data: (1) staying at home for as long as possible but avoiding crisis, (2) balancing risks proactively and anticipating triggers, (3) desires for the person living with dementia to be involved in the decision, and (4) the significance of funding in enabling choices about a care home move. Deciding on the timing of a care home move is context and person specific. Two professional groups with substantial experience of this among their client group both recommended proactive deliberation but funding was overall the deciding factor in the extent to which they considered choice was possible. Future research should avoid seeing all care home moves as negative and explore how practitioners can best encourage discussions prior to crisis point about care home options.


Understanding quit patterns from a randomized clinical trial: Latent classes, predictors, and long-term abstinence.
Tobacco dependence treatment is recognized as a dynamic, chronic process comprised of several specific phases. Of these phases, the Cessation phase is the most critical as it has demonstrated the strongest relation to quit success. Yet, little is understood about smoking trajectories during this period. The current study aimed to address gaps in the smoking research literature and advance understanding of the dynamic quit process unique to completing an integrated smoking treatment by evaluating quit behavior during the Cessation phase. Two hundred and sixty-seven treatment seeking smokers enrolled in a clinical trial to evaluate the efficacy of a novel, integrated smoking cessation treatment (46.1% male; Mage = 39.25, SD = 13.70) were included in the present study. Repeated-measure latent class analysis was employed to evaluate quit patterns from quit day through day 14 post-quit. Results supported a four-class solution: Consistent Quitters, Non-Quitters, Relapsers, and Delayed Quitters. Predictors of class membership included age, number of prior quit attempts, motivation to quit smoking, and quit day smoking urges. Moreover, class membership was significantly associated with 6-month abstinence. Results suggest that there are four relevant classes of quit behavior, each with specific predictor variables including age, motivation to quit, smoking urges, and number of quit attempts, and that these classes relate to long-term abstinence. These results have the potential to inform manualized smoking cessation treatment interventions based on relevant subgroups of quit behavior.


Identification of a cis-acting element responsible for negative regulation of the human UDP-glucose dehydrogenase gene expression.
The enzyme UDP-glucose dehydrogenase (UGDH) catalyzes the conversion of UDP-glucose to UDP-glucuronic acid, which is essential for the biosynthesis of complex carbohydrates such as hyaluronan in many cell types, and is required for detoxification of toxic compounds in the liver. We previously defined the 714 bp 5'-flanking region of the UGDH gene as the core promoter, with putative negative regulatory elements residing in the region upstream of it. In the present study, we delineated the region from nucleotide positions -1057 to -957 on the UGDH promoter to be responsible for the repression of promoter activity. A mutation at nucleotide -1003, which is contained within a motif predicted to be the response element for peroxisome proliferator receptor alpha (PPARalpha), abolished the suppression effect. DNA-protein interaction was observed at this motif by electrophoretic mobility shift assay. The proteins interacting with the PPRE-like repressor motif were purified by biotin-labeled DNA affinity chromatography. Subsequently, MALDI-TOF identified the purified proteins as a 62-kDa zinc finger and a 42-kDa beta-actin protein. Hence in this study we report the presence of an inhibitory cis-element in the distal region of the UGDH promoter that interacts with putative transcriptional repressors for the negative regulation of the UGDH gene.


[Peculiarities of blood supply of palatal tonsils and the potential risk of hemorrhage during tonsillectomy: the literature review and case report].
The present review encompasses the publications concerning peculiarities of blood supply of palatal tonsils, the frequency and variants of the anomalous structure of internal carotid artery. Analysis of the literature data has shown that the anomalous vascular structure is one of the important risk factors of the development of intra- and postoperative hemorrhage, besides redundant blood supply of the oropharynx, inflammatory changes in the tissue of tonsils and peritonsillar region. Special attention is given to the peculiarities of diagnostics of such conditions. The emphasis is laid on the importance of timely diagnostics of the anomalous structural changes in the main vessels of the neck prior to the surgical intervention on the pharynx. The analysis of the anomalous structure of internal carotid artery is presented.


Help signals provided by lymphokines modulate the activation and apoptotic programs induced by partially agonistic peptides in specific cytotoxic T lymphocytes.
Inefficient recognition of altered peptide ligands (APL) by specific CTL is believed to contribute to the failure of immune control over tumors and progressive viral infections. A link between deficient help signals and the appearance of CTL epitope mutants has been suggested by recent studies. However, the regulation of APL activity by immunologic help is not well understood. We analyzed the capacity of exogenous IL-2 and IL-15, which are physiologically produced by cells of the adaptive and innate immune system, respectively, to modulate proliferation, responsiveness to repeated stimulation and apoptotic programs triggered in specific CTL by either fully or partially agonistic peptide ligands. We show that signals induced by the lymphokines synergize with weak TCR signaling induced by partially agonistic APL, converting many of these peptides from inhibitory to stimulatory ligands. Some APL partially suppress the responsiveness of specific CTL to secondary stimulation, while this inhibitory effect is diminished if APL-stimulated cells are cultured in the presence of either of the lymphokines. We also demonstrate that IL-2 and IL-15 suppress up-regulation of the Bcl-2 family member Bim and induction of a death receptor-independent apoptotic program triggered by partially agonistic APL. Our results suggest that under conditions of insufficient immunologic help, partially agonistic APL may actively suppress specific CTL responses and become especially advantageous for immune escape of tumors or viruses.


Quercetin serves as the major component of Xiang-lian Pill to ameliorate ulcerative colitis via tipping the balance of STAT1/PPARγ and dictating the alternative activation of macrophage.
The traditional Chinese herbal formula, Xiang-lian Pill (XLP), is commonly prescribed for ulcerative colitis (UC) patients to relieve their clinical symptom. Nonetheless, the underlying cellular and molecular mechanisms of XLP's anti-UC effect remain incompletely understood. To evaluate the therapeutic effect and elucidate the possible working mechanisms of XLP in UC treatment. The major active component of XLP was also characterized. Colitis was induced in C57BL/6 mice with 3% dextran sulfate sodium (DSS) dissolved in drinking water for 7 consecutive days. The UC mice were grouped and treated with XLP (3640 mg/kg) or vehicle orally during the procedure of DSS induction. Mouse body weight, disease activity index (DAI) score and colon length were recorded. Histopathological changes and inflammatory cell infiltration were evaluated by pathological staining and flow cytometric analysis (FACS). Network pharmacology, bioinformatic analysis, widely targeted and targeted metabolomics analysis were performed to screen the potential effective ingredients and key targets. Bone marrow derived macrophages (BMDMs), peripheral blood mononuclear cells (PBMCs), RAW264.7 and THP-1 cells were used to dissect the anti-inflammatory effect of XLP. Oral administration of XLP ameliorated DSS induced mouse colitis, as evidenced by reduced DAI and colonic inflammatory destruction. FACS results demonstrated that XLP treatment effectively restored immune tolerance in colon, inhibited the generation of monocyte derived macrophages and skewed macrophage polarization into M2 phenotype. Network pharmacology analysis suggested that innate effector modules related to macrophage activation comprise the major targets of XLP, and the counter-regulatory STAT1/PPARγ signaling possibly serves as the critical downstream pathway. Subsequent experiments unveiled an imbalance of STAT1/PPARγ signaling in monocytes derived from UC patients, and validated that XLP suppressed LPS/IFN-γ induced macrophage activation (STAT1 mediated) but facilitated IL-4 induced macrophage M2 polarization (PPARγ dependent). Meanwhile, our data showed that quercetin served as the major component of XLP to recapitulate the regulatory effect on macrophages. Our findings revealed that quercetin serves as the major component of XLP that regulates macrophage alternative activation via tipping the balance of STAT1/PPARγ, which provides a mechanistic explanation for the therapeutic effect of XLP in UC treatment.


The pig as an animal model for the study of nitrosamine metabolism.
Surgical procedures have been developed that permit the sampling of portal blood, bile and hepatic blood in intact pigs. Animals so prepared have been used to study liver metabolism and biliary excretion of N-nitrosodimethylamine (NDMA) following oral and intravenous dosing.


Assessment of air purifier on efficient removal of airborne bacteria, Staphylococcus epidermidis, using single-chamber method.
We evaluated the efficiency of an air purifier using the single-chamber method for the effective removal of airborne Staphylococcus epidermidis, a nosocomial infection-causing bacterium. In this experiment, the bacterial strain S. epidermidis was injected using a nebulizer into the test chamber, which was similar to a consumer living space (60 m3). The microbial sampling was conducted via the air sampler method, and the reduction in S. epidermidis growth was monitored by performing three consecutive tests. Initially, a blank test was conducted to determine the natural decay rate and calibrate the experimental setup. After injecting the bacterial strain from 1240 to 11180 CFU per unit volume (m3), the natural decay rate showed a maximum deviation of 3.1% with a sampling error of 1.1% p at a confidence level of 95%. In addition, the particle size distribution in the test chamber was found to range from 0.3 to 5.0 μm, and a subsequent decrease in large-sized particles was observed with the operation of the air purifier, which is the size similar to that of suspended airborne bacteria. This can be used to assess the performance of the air purifier by calibrating the natural reduction value to the reduced operation value. Thus, the single-chamber technique is a promising approach for analyzing the removal efficacy of airborne bacteria from indoor air.


"I often have to explain to school staff what she needs". School experiences of non-autistic siblings growing up with an autistic brother or sister.
Recent autism research has evidenced a shift from psychological outcomes to contextualised approaches to understanding the varying needs of non autistic siblings of autistic children across different systems. Yet, there is limited research exploring the lived experiences of siblings in their school context. First, a group of school aged sibling advisors worked with the first author to codesign research aims, methods and dissemination practices around the topic of the school experiences of siblings who grow up with an autistic brother or sister in the UK. Then, 28 school-aged siblings of autistic children completed adapted photo-elicitation interviews, to discuss their school experiences. A background questionnaire was also administered to their parents and carers. Thematic analysis was employed. The master themes included: (i) Impact of home experiences in schoolwork, including limited personal time and sleep disruptions (ii) Siblings' school interactions impact on overall school experience, including a wide range of both typical and difficult experiences such as school day disruptions, (iii) Varied perceived levels of support and understanding, including emotional and/or educational support by family members and a sense of connectedness with peers and teachers who are autistic themselves or connected to someone with a diagnosis of autism. The results underline the ways home experiences can have an impact on school life of siblings, the positive contribution of the autistic school staff and/or staff who have an autistic family member and the need for an organisational culture of inclusivity and widespread acceptance and awareness around issues of neurodiversity. Our findings suggest several implications for school psychologists in core functions of the educational psychologists' role including training, consultation, assessment, and whole school support. The datasets generated for this study are not readily available because they include sensitive data (photos of siblings' houses, family members, personal objects, and school timetables). Requests to access the datasets should be directed to corresponding author.


The best practice tariff and hip fractures: How can Northern Ireland keep up?
Current hip fractures guidelines recommend surgery within 36 h of admission. The 2011 National Hip Fracture Database (NHFD) report shows our institute has the fewest patients meeting this target (9%). Northern Irelands' exclusion from the "Best Practice Tariff" means no incentive-led treatment or prioritisation of hip fracture patients. We performed a systematic review of post-operative results to highlight deficiencies in delivery of patient care. We reviewed 702 patients admitted between September 2009 and April 2012. Patients were prospectively identified and added to our Fracture Outcome and Research Database (FORD). Results were compared to national average values from the NHFD. 16.7% of patients met the 36-h target to theatre compared to the UK average of 66%. 81.7% underwent a pre-operative orthogeriatric review. The main reasons for surgical delay were inadequate theatre space (58%) and medically unfit patients (29%). After exclusion of medically unfit patients, medically fit patients were divided into delayed surgery and not delayed categories. Medically fit patients who had delayed surgery had inferior outcomes- longer hospital stay and higher mortality as an inpatient and at 30 days. Without a change in funding, Northern Ireland will struggle to compete with the UK mainland and decrease mortality in this patient group.


Avian LH and FSH: comparison of several radioimmunoassays.
Comparisons were made between various LH and FSH radioimmunoassays currently being used to measure avian hormones. The two LH assays were the homologous chicken system of Follett et al. (1972) and the turkey assay of Burke et al. (1979). These assays were also used in heterologous arrangement by interchanging the iodinated LH fractions and antisera. Five FSH assays were analyzed: two homologous chicken systems (Scanes et al., 1977; Sakai and Ishii, 1980). an assay based on mammalian materials (rat FSH and anti-ovine FSH antiserum, and one using labelled turkey FSH (Burke et al., 1979) with an anti-chicken FSH antiserum. The potencies of purified chicken and turkey gonadotrophin preparations and of a range of plasma samples from Japanese quail were measured in each assay. The two LH systems showed some degree of species specificity, such that chicken LH was more active than turkey LH in the chicken assay, whereas the reverse was true in the turkey LH assay. The potency estimates of the purified hormones in the various FSH assays were very consistent. The qualitative changes in plasma hormone levels were similar in all assays, although there were some differences in the magnitude of the responses.


An investigation on the cyclic temperature-dependent performance behaviors of ultrabright air-stable QLEDs.
The aerobic and thermal stability of quantum-dot light-emitting diodes (QLEDs) is an important factor for the practical applications of these devices under harsh environmental conditions. We demonstrate all-solution-processed amber QLEDs with an external quantum efficiency (EQE) of > 14% with almost negligible efficiency roll-off (droop) and a peak brightness of > 600,000 cd/m2, unprecedented for QLEDs fabricated under ambient air conditions. We investigate the device efficiency and brightness level at a temperature range between - 10 and 85 °C in a 5-step cooling/heating cycle. We conducted the experiments at brightness levels higher than 10,000 cd/m2, required for outdoor lighting applications. Our device performance proves thermal stability, with minimal standard deviation in the performance parameters. Interestingly, the device efficiency parameters recover to the initial values upon returning to room temperature. The variations in the performance are correlated with the modification of charge transport characteristics and induced radiative/non-radiative exciton relaxation dynamics at different temperatures. Being complementary to previous studies on the subject, the present work is expected to shed light on the potential feasibility of realizing aerobic-stable ultrabright droop-free QLEDs and encourage further research for solid-state lighting applications.


Complementation Assays for Co-chaperone Function.
The development of mutant microorganisms lacking J domain proteins (JDPs; formerly called Hsp40s) has enabled the development of complementation assays for testing the co-chaperone function of JDPs. In these assays, an exogenously expressed novel JDP is tested for its ability to functionally substitute for a non-expressed or nonfunctional endogenous JDP(s) by reversing a stress phenotype. For example, the in vivo functionality of prokaryotic JDPs can be tested on the basis of their ability to reverse the thermosensitivity of a dnaJ cbpA mutant strain of the bacterium Escherichia coli (OD259). Similarly, the in vivo functionality of eukaryotic JDPs can be assessed in a thermosensitive ydj1 mutant strain of the yeast Saccharomyces cerevisiae (JJ160). Here we outline the use of these thermosensitive microorganisms in complementation assays to functionally characterize a JDP from the bacterium, Agrobacterium tumefaciens (AgtDnaJ), and a JDP from the trypanosomal parasite, Trypanosoma cruzi (TcJ2).


Proof of concept: Comparative accuracy of semiautomated VR modeling for volumetric analysis of the heart ventricles.
Simpson's rule is generally used to estimate cardiac volumes. By contrast, modern methods such as Virtual Reality (VR) utilize mesh modeling to present the object's surface spatial structure, thus enabling intricate volumetric calculations. In this study, two types of semiautomated VR models for cardiac volumetric analysis were compared to the standard Philips dedicated cardiac imaging platform (PDP) which is based on Simpson's rule calculations. This retrospective report examined the cardiac computed tomography angiography (CCTA) of twenty patients with atrial fibrillation obtained prior to a left atrial appendage occlusion procedure. We employed two VR models to evaluate each CCTA and compared them to the PDP: a VR model with Philips-similar segmentations (VR-PS) that included the trabeculae and the papillary muscles within the luminal volume, and a VR model that only included the inner blood pool (VR-IBP). Comparison of the VR-PS and the PDP left ventricle (LV) volumes demonstrated excellent correlation with a ρ c of 0.983 (95% CI 0.96, 0.99), and a small mean difference and range. The calculated volumes of the right ventricle (RV) had a somewhat lower correlation of 0.89 (95% CI 0.781, 0.95), a small mean difference, and a broader range. The VR-IBP chamber size estimations were significantly smaller than the estimates based on the PDP. Simpson's rule and polygon summation algorithms produce similar results in normal morphological LVs. However, this correlation failed to emerge when applied to RVs and irregular chambers. The findings suggest that the polygon summation method is preferable for RV and irregular LV volume and function calculations.


Carcinogenic effects of prolonged daily low-emission phototherapy in psoriasis.
Low-dose UV treatment has been shown to be effective in mild psoriasis. However, the prolonged use of this treatment modality may raise concerns about its safety. These concerns are mainly focused on potential carcinogenic risks and overuse of this treatment modality. This study was set out to evaluate possible carcinogenic risks of prolonged low-dose phototherapy. Three groups of psoriasis patients were evaluated: patients with local treatment only (n = 15); low-dose UV treatment at home for at least 18 months (n = 39); and patients with conventional NB-UVB (n = 8). Patients underwent visual inspection for signs of photoageing, and p53, CPDs and γH2AX were measured in skin biopsies. Patients undergoing low-dose phototherapy answered a survey about their recent patterns of use in a survey. In the skin biopsies, low-dose UV treatment caused a lower amount of CPDs (p = .016) and p53 (p = .015) than NB-UVB. γH2AX did not show a significant difference. Self-report in patients undergoing low-dose phototherapy showed only one case of overuse (2.7%). Visual skin inspection showed no difference in signs of photoageing in the three groups. Prolonged treatment with low-dose UV for 18 months appears at least as safe as a course of conventional NB-UVB.


Associated factors of neonatal near miss among newborns of adolescent mothers in Brazil.
To identify the associated factors of neonatal near miss among newborns of Brazilian adolescents and to compare their occurrence in young women aged 12 to 16 years and 17 to 19 years. Cross-sectional, hospital-based study, using data from the study Nascer no Brasil ("Birth in Brazil") on puerperal adolescents and their newborns in all regions of Brazil. Multiple and univariate logistic regression were employed to identify the associated factors of neonatal near miss. The following factors were found to be associated to neonatal near miss among newborns of adolescent mothers: public source of payment (OR = 4.57, 95% CI = 2.02-10.32), having to seek help in different maternity hospitals (OR = 1.52; 95% CI = 1.05-2.20), and maternal near miss (OR = 5.92; 95% CI = 1.94-18.05), in addition to a record of low weight in a previous pregnancy (OR = 3.12; 95% CI = 1.61-6.04) and twin pregnancy (OR = 7.49; 95% CI = 3.28-16.82). Neonatal near miss affected newborns of adolescent mothers in both age groups equally. Also, the determinant factors of neonatal near miss can be mostly reduced with qualified prenatal, labor, and birth care.


Tazobactam/ceftolozane and tobramycin combination therapy in extensively drug-resistant Pseudomonas aeruginosa infections in severe burn injury: a case report.
Combination therapy with tazobactam/ceftolozane (TAZ/CTLZ) and high-dose aminoglycosides has been reported to be efficacious in extensively drug-resistant (XDR)-Pseudomonas aeruginosa infection. However, there are no reports of efficacy in XDR-P. aeruginosa infection for combination therapy with low-dose aminoglycosides and TAZ/CTLZ. Herein, we describe a rare case of severe burn injury patients with persistent bacteremia due to XDR-P. aeruginosa, which was successfully treated with TAZ/CTLZ and low-dose tobramycin (TOB). A 31-year-old man was admitted to the intensive care unit with severe burn injury involving 52% of the total body surface area and a prognostic burn index of 79.5. The patient had recurrent bacterial infections since admission, and blood cultures collected on the 37th day of admission revealed the presence of P. aeruginosa strains that were resistant to all β-lactams and amikacin (AMK). The results of the antimicrobial synergistic study showed no synergistic effect of low-dose meropenem (MEPM) and AMK combination therapy. The patient had acute renal failure, and it was difficult to increase the dose of MEPM and AMK, respectively. Thus, we initiated TAZ/CTLZ 1.5 g/8 h instead of the AMK and MEPM combination therapy on the 43rd day of hospitalization. Low-dose TAZ/CTLZ was continued because of prolonged renal dysfunction and resulted in a transient clinical improvement. However, the dosage of TAZ/CTLZ could be increased as the renal function improved, but despite an increased TAZ/CTLZ dose, bacteremia persisted, and the blood cultures remained positive. Thus, TOB was added to TAZ/CTLZ at low doses for synergistic effect against Gram-negative bacteria. Blood cultures collected after initiation of combination therapy with TAZ/CTLZ and low-dose TOB were negative on two consecutive follow-up evaluations. Thereafter, although the patient had several episodes of fever and increased inflammatory response, blood cultures consistently tested negative, and all of the wounds healed. On the 93rd day, due to the good healing progress, the patient was transferred to another hospital. TAZ/CTLZ and low-dose TOB combination therapy showed the potential for synergistic effects. Our present report suggests a novel synergistic treatment strategy for rare cases that are refractory to the treatment of infections, such as XDR-P. aeruginosa infection.


The Impact of Flap Creation Methods for Sub-Bowman's Keratomileusis (SBK) on the Central Thickness of Bowman's Layer.
To determine the impact of flap creation methods for sub-Bowman's keratomileusis (SBK) on central Bowman's layer thickness. SBK flaps were made by Moria microkeratome for 20 subjects and by femtosecond (FEMTO) laser for 21 subjects. Corneal sublayer thicknesses were measured by ultra-high resolution optical coherence tomography before SBK and at 1 day, 1 week, 2 weeks, and 1 month afterwards. Each subject was imaged twice on each visit. Thicknesses of central epithelium, Bowman's layer, flap, and total cornea were calculated using a custom-made automated image processing algorithm. The repeatability of sublayer thickness measurements was tested by the intraclass correlation coefficient (ICC) and by the coefficient of repeatability (CoR) at 1 week post-SBK. ICCs of the Moria and FEMTO groups were ≥ 0.959 and ≥ 0.961 respectively for all sublayer measurements. The segmentation CoRs were less than 6.78% and 5.63% respectively. For both groups, microdistortions were present in the epithelium and Bowman's layer after SKB. The flap thickness of the Moria group was 9.8 μm (95% confidence interval: 4.8 - 14.8 μm) thinner than the FEMTO group one day after SBK (independent samples t-test, P < 0.05). Bowman's layer became thicker by 1.6 ± 1.1 μm and 1.7 ± 1.6 μm one day post-SBK for the Moria and FEMTO groups (repeated ANOVA, P < 0.05) and then remained stable. Corneal and sublayer thickness were similar between the two groups. Central Bowman's layer thickness increased 1 day post-SBK. Flap creation by Moria microkeratome and femtosecond laser did not have significantly different impacts on Bowman's layer thickness following SBK. Chinese Clinical Trial Registry (ChiCTR) NO: ChiCTR-OCH-14004525.


Identity status research: implications for career counseling.
The purpose of this paper is to describe an empirical approach to the study of adolescence and to apply research findings to vocational counseling. The study of identity status has enriched and supported Erikson's theory of psychosocial development. Case histories of hypothetical clients in the four identity statuses are presented and different approaches for counseling with such clients are suggested.


Imipramine hydrochloride: pharmacodynamic effects on lower urinary tract of female dogs.
Our study of the pharmacodynamics of imipramine hydrochloride of the female canine lower urinary tract indicates the primary mode of action to be the stimulation of alpha adrenergic neuroreceptors in the bladder neck and urethra. This stimulation results in increased resting urethral pressure, adequate sphincter closure, possibly an increase in the bladder capacity and efficient urinary control. Imipramine had no anticholinergic effect on the bladder and the urethra. It also appears unlikely that in enuretic patients imipramine acts by central augmentation of the adrenergic system. No change was noticed in the intravesical or arterial pressures.


Evaluation of marking of peer marking in oral presentation.
Peer marking is an important skill for students, helping them to understand the process of learning and assessment. This method is increasingly used in medical education, particularly in formative assessment. However, the use of peer marking in summative assessment is not widely adopted because many teachers are concerned about biased marking by students of their peers. The aim of this study was to investigate whether marking of summative peer assessment can improve the reliability of peer marking. In a retrospective analysis, the peer-marking results of a summative assessment of oral presentations of two cohorts of students were compared. One group of students was told that their peer marks would be assessed against a benchmark consisting of the average of examiner marks and that these scores together with the peer and examiner marks would form their final exam results. The other group of students were just informed that their final exam results would be determined based on the examiner and peer marks. Based on examiner marks, both groups of students performed similarly in their summative assessment, agreement between student markers was less consistent and more polar than the examiners. When compared with the examiners, students who were told that their peer marking would be scored were more generous markers (their average peer mark was 2.4 % points higher than the average examiner mark) while students who were not being scored on their marking were rather harsh markers (their average peer mark was 4.2 % points lower than the average examiner mark), with scoring of the top-performing students most affected. Marking of peer marking had a small effect on the marking conduct of students in summative assessment of oral presentation but possibly indicated a more balanced marking performance.


Subcutaneous Phaeohyphomycosis Caused by Pyrenochaeta romeroi in a Rheumatoid Arthritis Patient: A Case Report with Review of the Literature.
Pyrenochaeta romeroi is a rare fungal agent of chronic, suppurative subcutaneous infections leading to mycetoma. It is an unusual cause of deep, non-mycetomatous infections. We herein present review of the literature along with a case of 61-year-old Indian female with rheumatoid arthritis who developed subcutaneous phaeohyphomycosis caused by Pyrenochaeta romeroi. It posed a diagnostic challenge, as the culture from fine-needle aspirate revealed a non-sporulating dematiaceous mould, which was the only supportive tool for its diagnosis and initiation of the therapy. However, it was the molecular sequencing which played the pivotal role in clinching the final aetiological diagnosis. To the best of our knowledge, this is the 20th case of Pyrenochaeta species infection occurring worldwide and first case report of subcutaneous phaeohyphomycosis caused by Pyrenochaeta romeroi in a rheumatoid arthritis patient.


Intercellular adhesion molecule-1 concentration, in utero, decreases after antibiotic treatment.
A parturient suffering from preterm premature rupture of membranes at 29-weeks of gestation was hospitalized and staphylococcus was detected in her amniotic fluid. After treatment with antibiotics she delivered a healthy neonate three weeks later. ICAM-1 levels decreased by 20 fold correlating with elimination of the bacteria and prolongation of the pregnancy.


Refractive outcomes after DMEK: meta-analysis.
In this meta-analysis and systematic literature review of refractive outcomes after Descemet membrane endothelial keratoplasty (DMEK), the extent of the refractive shift and an overview of reasons for refractive shift after DMEK are provided. The PubMed library was screened for articles containing the terms "Descemet membrane endothelial keratoplasty," "DMEK," "Descemet membrane endothelial keratoplasty combined with cataract surgery," "triple-DMEK" combined with "refractive outcomes," "refractive shift," and "hyperopic shift." The refractive outcomes after DMEK were analyzed and compared using a fixed and random effects model. The overall mean change of the spherical equivalent outcome when compared with the preoperative value in cases of DMEK or when compared with the preoperative target refraction in cases of DMEK combined with cataract surgery was +0.43 diopters (D) (95% CI, 0.31-0.55). When DMEK is combined with cataract surgery, a target refraction of -0.5 D is recommended to achieve emmetropia. Changes in the posterior corneal curvature are identified as the main cause of the refractive hyperopic shift.


Inhibitory effects of polysorbate 80 on MRSA biofilm formed on different substrates including dermal tissue.
Methicillin-resistant Staphylococcus aureus (MRSA) forms biofilms on necrotic tissues and medical devices, and causes persistent infections. Surfactants act on biofilms, but their mode of action is still unknown. If used in the clinic, cytotoxicity in tissues should be minimized. In this study, we investigated the inhibitory effect of four different surfactants on MRSA biofilm formation, and found that a nonionic surfactant, polysorbate 80 (PS80), was the most suitable. The biofilm inhibitory effects resulted from the inhibition of bacterial adhesion to substrates rather than biofilm disruption, and the effective dose was less cytotoxic for 3T3 fibroblasts. However, the effects were substrate-dependent: positive for plastic, silicon, and dermal tissues, but negative for stainless-steel. These results indicate that PS80 is effective for prevention of biofilms formed by MRSA on tissues and foreign bodies. Therefore, PS80 could be used in medical practice as a washing solution for wounds and/or pretreatment of indwelling catheters.


eNOS polymorphisms on male infertility: An updated systematic review and meta-analysis.
This meta-analysis was performed to examine the association of 3 endothelial nitric oxide synthase (eNOS) gene polymorphisms with male infertility. The literature on the relation between the mutant of eNOS and male infertility before July 1, 2022, was conducted in Pubmed, Medline, and Web of Science. The search strategy is as follows: (eNOS OR ECNOS OR nitric oxide synthase 3 OR NOS3) AND (polymorphism OR mutation OR variation OR SNP OR genotype) AND (male infertility). Statistical analysis was performed with the web of MetaGenyo, Stata 12, trial sequential analysis 0.9Beta, and the web of GTEx. Overall, 13 studies (26 case-controls) were included involving 6518 cases and 5461 controls for 3 polymorphisms (rs2070744, rs1799983, rs61722009) of eNOS. We found that eNOS rs2070744 was correlated with an increased risk of male infertility (C vs. T: odds ratio [OR], 1.48; 95% confidence interval [CI], [1.19-1.85]; CC vs. TT: OR, 2.59; 95% CI, [1.40-4.80]; CT vs. TT: OR, 1.17; 95% CI, [1.00-1.38]; CC vs. CT + TT: OR, 2.50; 95% CI, [1.35-4.62]; CC + CT vs. TT: OR, 1.41; 95% CI, [1.21-1.64]). And eNOS rs1799983 was correlated with an increased risk of male infertility (allele contrast T vs. G: OR, 1.41; 95% CI, [1.01-1.96]; P = .043; recessive model TT vs. TG + GG: OR, 2.00; 95% CI, [1.03-3.90]; P = .042). In the stratified analysis of rs61722009, we found Asians might be correlated with an increased risk of male infertility (4a vs. 4b: OR, 1.50; 95% CI, [0.94-2.38]; 4a4a vs. 4b4b: OR, 2.56; 95% CI, [0.70-9.38]; 4a4b vs. 4b4b: OR, 1.36; 95% CI, [0.87-2.13]; 4a4a vs. 4a4b + 4b4b: OR, 2.57; 95% CI, [0.91-7.30]; 4a4a + 4a4b vs. 4b4b: OR, 1.44; 95% CI, [0.87-2.40]). The eNOS rs2070744 polymorphism and rs1799983 are associated with the risk of male infertility, and rs61722009 might be a risk factor for Asians.


Treatment strategy for acute myocarditis in pediatric patients requiring emergency intervention.
Patients with acute myocarditis present with a wide range of symptoms. Treatment strategies for pediatric patients with circulatory failure comprise extracorporeal membrane oxygenation (ECMO), emergency temporary pacing, and pharmacotherapy. However, they remain controversial. ECMO is an effective treatment but gives rise to several complications; the goal is therefore to avoid excessive treatment as much as possible. We aimed to evaluate the importance of electrocardiogram findings in differentiating severity and establish an appropriate treatment strategy in pediatric patients with acute myocarditis who required emergency interventions. This retrospective study enrolled pediatric patients admitted to and treated in our hospital for acute myocarditis between April 1983 and December 2021. Patients were retrospectively divided into whether circulatory failure occurred (ECMO or temporary pacing was needed; emergency intervention group) or not (pharmacotherapy alone). Of the 26 pediatric patients, 11 experienced circulatory failure while 15 did not. In the circulatory failure group, six patients were treated with ECMO (ECMO group) and five patients with temporary pacing (pacing group). In the pacing group, all patients were diagnosed with complete and/or advanced atrioventricular block (CAVB and/or advanced AVB) and narrow QRS. Furthermore, these patients improved only with temporary pacing and pharmacotherapy, without requiring ECMO. Wide QRS complexes (QRS ≥ 0.12 ms) with ST-segment changes were detected on admission in five of six patients in the ECMO group and none in the pacing group (P = 0.015). Although all patients in the ECMO group experienced complications, none did in the pacing group (P < 0.008). Regarding emergency intervention for acute myocarditis, ECMO or temporary pacing could be determined based on electrocardiogram findings, particularly wide QRS complexes with ST-segment changes on admission. It is important to promptly introduce ECMO in patients with wide QRS complexes with ST-segment changes, however, patients with CAVB and/or advanced AVB and narrow QRS could improve without undergoing ECMO. Therefore, excessive treatment should be avoided by separating ECMO from temporary pacing based on electrocardiogram findings on admission.


Cellular stress and nucleolar function.
All organisms sense and respond to conditions that stress their homeostatic mechanisms. Here we review current studies showing that the nucleolus, long regarded as a mere ribosome producing factory, plays a key role in monitoring and responding to cellular stress. After exposure to extra- or intracellular stress, cells rapidly down-regulate the synthesis of ribosomal RNA. Impairment of nucleolar function in response to stress is accompanied by perturbation of nucleolar structure, cell cycle arrest and stabilization of p53. The nucleolar target for down-regulation of rDNA transcription is TIF-IA, an essential transcription factor that modulates the activity of RNA polymerase I (Pol I). Upon stress, TIF-IA is phosphorylated by c-Jun N-terminal kinase 2 (JNK2). Phosphorylation prevents TIF-IA from interaction with Pol I, thereby impairing transcription complex formation and rRNA synthesis. Furthermore, stress-induced inactivation of TIF-IA is accompanied by translocation of TIF-IA from the nucleolus to the nucleoplasm. These findings, together with other data showing stress-induced release of nucleolar proteins to carry out other regulatory functions, reinforce the growing realization that nucleoli orchestrate the chain of events the cell uses to properly respond to stress signals.


Correction to: The Prevalence of Mental Illness and Substance Abuse Among Rural Latino Adults with Multiple Adverse Childhood Experiences in California.
The original version of this article unfortunately published without acknowledgement section. The complete funding information is given below.


Stromal-epithelial crosstalk regulates kidney progenitor cell differentiation.
Present models suggest that the fate of the kidney epithelial progenitors is solely regulated by signals from the adjacent ureteric bud. The bud provides signals that regulate the survival, renewal and differentiation of these cells. Recent data suggest that Wnt9b, a ureteric-bud-derived factor, is sufficient for both progenitor cell renewal and differentiation. How the same molecule induces two seemingly contradictory processes is unknown. Here, we show that signals from the stromal fibroblasts cooperate with Wnt9b to promote differentiation of the progenitors. The atypical cadherin Fat4 encodes at least part of this stromal signal. Our data support a model whereby proper kidney size and function is regulated by balancing opposing signals from the ureteric bud and stroma to promote renewal and differentiation of the nephron progenitors.


Inactivation of RNA and DNA viruses in water by copper and silver ions and their synergistic effect.
Cu and Ag have been used as bactericidal agents since ancient times, yet their antiviral capacity in water remains poorly understood. This study tested the effect of copper (Cu) and silver (Ag) on model RNA and DNA viruses MS2 and PhiX 174 in solution at pH 6-8. Cu caused MS2 inactivation with similar rates at pH 6 and 7 but was inert towards PhiX 174 regardless of pH. Ag inactivated both viruses, causing denaturation of MS2 and loss of capsid spikes in PhiX 174. Ag inactivation rates were pH dependent and increased with increasing pH. At pH 8, 6.5 logs of PhiX were inactivated after 3 h and 3 logs of MS2 after only 10 min. The combined use of Cu and Ag revealed synergy in disinfecting MS2 at pH ≥ 7. Although metal concentrations used were higher than the desired values for drinking water treatment, the results prove a promising potential of Cu and Ag combinations as efficient viricidal agents.


Membrane-Induced Technique for the Management of Combined Soft Tissue and Osseous Defects.
The induced membrane technique is a simple, effective, and reproducible treatment method for segmental bone defects. It is a 2-stage approach that requires eventual autologous bone graft to manage the deficit. The first stage requires debridement of all nonviable tissue while preserving a healthy soft tissue envelope. A polymethylmethacrylate is implanted between the osseous segments to maintain length. The osseous defect can be stabilized internally or externally. During the second stage, a vascularized induced membrane is formed and produces multiple growth factors. The induced membrane technique is a valuable option for limb salvage in cases of segmental bone defects.


Carbapenems: special properties contributing to their activity.
Imipenem is a beta-lactam antibiotic that inhibits most clinical isolates of staphylococci, Enterobacteriaceae, and streptococci, excluding enterococci, at 1 microgram/ml or less. Resistance can develop in methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and Serratia marcescens, albeit infrequently. Pseudomonas maltophilia is intrinsically resistant to imipenem. Many strains of Enterobacter cloacae, Clostridium freundii, and S. marcescens resistant to the aminothiazolyl cephalosporins are susceptible to imipenem, but tend to have higher minimal inhibitory concentrations. In general, imipenem inhibits organisms resistant to other beta-lactams and aminoglycosides. Imipenem binds to PBP-2 and rapidly kills most bacteria which it inhibits. Imipenem is highly stable against attack by beta-lactamases of both plasmid and chromosomal origin, and is more stable by several thousand-fold than earlier beta-lactamase stable compounds. It acts as a suicide inhibitor of beta-lactamases. Imipenem does induce beta-lactamases, but the activity of imipenem against isolates containing induced beta-lactamases is not decreased and it appears not to be susceptible to the trapping that occurs with some of the cephalosporins. Imipenem acts synergistically with aminoglycosides against a wide variety of bacteria, but this is most readily demonstrated for Streptococcus faecalis, S. aureus, and P. aeruginosa organisms which show a difference between inhibition and killing. Overall, the excellent activity of imipenem is the result of (1) the lack of a permeability barrier; (2) high affinity for PBP-2, a critical protein in cell wall synthesis in gram-negative bacteria, and for critical penicillin-binding proteins of gram-positive species; and, above all, (3) its great beta-lactamase stability.


Usefulness of natriuresis to predict in-hospital diuretic resistance.
Urinary sodium excretion predicts long-term adverse events after discharge in patients with acute heart failure (AHF). The role of natriuresis as an early marker of poor diuretic response during an AHF episode has been scarcely investigated. We sought to evaluate whether early natriuresis or its change during heart failure hospitalization is associated with the development of in-hospital diuretic resistance (DR). This was a prospective, observational single center study of consecutive patients with AHF. Urine electrolytes were estimated from a spot urine sample within the first 6 hours following the first diuretic dose and 48 hours after admission. In-hospital DR was defined as poor diuretic response based on diuretic efficiency metrics and persistent congestion despite an intensive diuretic protocol. Between January and December 2018, 143 patients were admitted for AHF. Of these, 102 fulfilled the inclusion criteria (60% males, median age 77 years [interquartile range [IQR]: 69-83), and 20 patients (19.6%) met the definition of DR. Early natriuresis was lower in patients with DR than in non-resistant patients (46 mEq/L [IQR: 38.5-80.0] vs 97.5 mEq/L [IQR: 70.5-113.5], P<0.001). Urinary sodium <50 mEq/L increased the risk of developing in-hospital DR (risk ratio: 5.011 [95% confidence interval 2.408-10.429], P<0.001). The area under the receiver operating characteristic curve for early natriuresis to predict DR was 0.791 (95% confidence interval 0.681-0.902, P<0.001). Initial natriuresis can predict in-hospital DR. Patients with urinary sodium <50 mEq/L have an increased risk of early resistance to diuretic treatment.


Attentional biases to emotional stimuli: Key components of the RDoC constructs of sustained threat and loss.
Biased attention to emotional stimuli plays a key role in the RDoC constructs of Sustained Threat and Loss. In this article, we review approaches to assessing these biases, their links with psychopathology, and the underlying neural influences. We then review evidence from twin and candidate gene studies regarding genetic influences on attentional biases. We also discuss the impact of developmental and environmental influences and end with a number of suggestions for future research in this area.


Bacterial envelope stress responses: Essential adaptors and attractive targets.
Millions of deaths a year across the globe are linked to antimicrobial resistant infections. The need to develop new treatments and repurpose of existing antibiotics grows more pressing as the growing antimicrobial resistance pandemic advances. In this review article, we propose that envelope stress responses, the signaling pathways bacteria use to recognize and adapt to damage to the most vulnerable outer compartments of the microbial cell, are attractive targets. Envelope stress responses (ESRs) support colonization and infection by responding to a plethora of toxic envelope stresses encountered throughout the body; they have been co-opted into virulence networks where they work like global positioning systems to coordinate adhesion, invasion, microbial warfare, and biofilm formation. We highlight progress in the development of therapeutic strategies that target ESR signaling proteins and adaptive networks and posit that further characterization of the molecular mechanisms governing these essential niche adaptation machineries will be important for sparking new therapeutic approaches aimed at short-circuiting bacterial adaptation.


Electroconvulsive seizures activate anorexigenic signals in the ventromedial nuclei of the hypothalamus.
The ventromedial nucleus of the hypothalamus (VMH) plays an important role in feeding and energy homeostasis. Electroconvulsive seizure (ECS) therapy is highly effective in the treatment of several psychiatric diseases, including depression, but may also have beneficial effects in other neurological diseases. Although it has been reported that the neurons of the VMH are strongly activated by ECS stimulation, the specific effects of ECS in this hypothalamic subnucleus remain unknown. To address this issue, we investigated the changes in gene expression in microdissected-VMH samples in response to ECS in mice, and examined the behavioral effects of ECS on feeding behavior. ECS significantly induced the expression of immediate-early genes such as Fos, Fosb, and Jun, as well as Bdnf, Adcyap1, Hrh1, and Crhr2 in the VMH. Given that signals of these gene products are suggested to have anorexigenic roles in the VMH, we also examined the effect of ECS on food intake and body weight. Repeated ECS had a suppressive effect on food intake and body weight gain under both regular and high-fat diet conditions. Furthermore, gold-thioglucose-induced hypothalamic lesions, including the VMH and the arcuate nucleus, abolished the anorexigenic effects of ECS, indicating the requirement for the activation of the hypothalamus. Our data show an effect of ECS on increased expression of anorexigenic factors in the VMH, and suggest a role in the regulation of energy homeostasis by ECS.


Effects of maternal nutrient restriction, intrauterine growth restriction, and glucocorticoid exposure on phosphoenolpyruvate carboxykinase-1 expression in fetal baboon hepatocytes in vitro.
The objective of this study was to develop a cell culture system for fetal baboon hepatocytes and to test the hypotheses that (i) expression of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase-1 (PEPCK-1) is upregulated in hepatocytes isolated from fetuses of nutrient-restricted mothers (MNR) compared with ad libitum-fed controls (CTR), and (ii) glucocorticoids stimulate PEPCK-1 expression. Hepatocytes from 0.9G CTR and MNR fetuses were isolated and cultured. PEPCK-1 protein and mRNA levels in hepatocytes were determined by Western blot and quantitative PCR, respectively. Fetuses of MNR mothers were intrauterine growth restricted (IUGR). Feasibility of culturing 0.9G fetal baboon hepatocytes was demonstrated. PEPCK-1 protein levels were increased in hepatocytes isolated from IUGR fetuses, and PEPCK-1 mRNA expression was stimulated by glucocorticoids in fetal hepatocytes. Cultured fetal baboon hepatocytes that retain their in vivo phenotype provide powerful in vitro tools to investigate mechanisms that regulate normal and programmed hepatic function.


Magnetic resonance spectroscopy: current and future applications in psychiatric research.
Magnetic resonance spectroscopy (MRS) provides a useful method for studying a number of psychotropic medications and metabolites in human brain in vivo. New insights regarding the pharmacokinetic and pharmacodynamic properties of psychotropic medications in the target organ (i.e., brain) have been obtained using lithium-7 MRS and fluorine-19 MRS. Both proton and phosphorus-31 MRS have significantly enhanced our knowledge of the pathophysiology of a number of psychiatric disorders by providing estimates of brain concentrations of several important cerebral metabolites. Efforts are also being made to link MRS measures of cerebral metabolism with neurophysiologic and neurocognitive processes. Ongoing improvement and refinement in MRS techniques, including the installation of scanners with increased magnetic field strength and better methods of data processing, will improve both spatial and temporal resolution. In addition, efforts to develop multisite research studies may result in greater standardization of MRS procedures and methods for interpretation of results. In this review, the current status of MRS applications in psychiatric research is reviewed, and new frontiers and possible future developments are discussed.


First molecular description, phylogeny and genetic variation of Taenia hydatigena from Nigerian sheep and goats based on three mitochondrial genes.
Cysticercosis caused by the metacestode larval stage of Taenia hydatigena is a disease of veterinary and economic importance. A considerable level of genetic variation among isolates of different intermediate hosts and locations has been documented. Generally, data on the genetic population structure of T. hydatigena is scanty and lacking in Nigeria. Meanwhile, similar findings in other cestodes like Echinococcus spp. have been found to be of epidemiological importance. Our aim, therefore, was to characterize and compare the genetic diversity of T. hydatigena population in Nigeria based on three mitochondrial DNA markers as well as to assess the phylogenetic relationship with populations from other geographical regions. In the present study, we described the genetic variation and diversity of T. hydatigena isolates from Nigerian sheep and goats using three full-length mitochondrial genes: the cytochrome c oxidase subunit 1 (cox1), NADH dehydrogenase subunit 1 (nad1), and NADH dehydrogenase subunit 5 (nad5). The median-joining network of concatenated cox1-nad1-nad5 sequences indicated that T. hydatigena metacestodes of sheep origin were genetically distinct from those obtained in goats and this was supported by high FST values of nad1, cox1, and concatenated cox1-nad1-nad5 sequences. Genetic variation was also found to be higher in isolates from goats than from sheep. To the best of our knowledge, the present study described the genetic variation of T. hydatigena population for the first time in Nigeria using full-length mitochondrial genes and suggests the existence of host-specific variants. The population indices of the different DNA markers suggest that analysis of long mitochondrial DNA fragments may provide more information on the molecular ecology of T. hydatigena. We recommend that future studies employ long mitochondrial DNA sequence in order to provide reliable data that would explain the extent of genetic variation in different hosts/locations and the biological and epidemiological significance.


Experimental demonstration of dynamic thermal regulation using vanadium dioxide thin films.
We present an experimental demonstration of passive, dynamic thermal regulation in a solid-state system with temperature-dependent thermal emissivity switching. We achieve this effect using a multilayered device, comprised of a vanadium dioxide (VO2) thin film on a silicon substrate with a gold back reflector. We experimentally characterize the optical properties of the VO2 film and use the results to optimize device design. Using a calibrated, transient calorimetry experiment we directly measure the temperature fluctuations arising from a time-varying heat load. Under laboratory conditions, we find that the device regulates temperature better than a constant emissivity sample. We use the experimental results to validate our thermal model, which can be used to predict device performance under the conditions of outer space. In this limit, thermal fluctuations are halved with reference to a constant-emissivity sample.


Recombinant Rv3261 protein of Mycobacterium tuberculosis induces apoptosis through a mitochondrion-dependent pathway in macrophages and inhibits intracellular bacterial growth.
Mycobacterium tuberculosis (Mtb) is an intracellular pathogen known to persist in host cells. The apoptotic response of macrophages serves as a defense mechanism to inhibit the growth of intracellular bacteria, the failure of which can favor the spread of the pathogen to new cells. However, the mycobacterial components that regulate cell death and the related underlying mechanisms remain poorly understood. In this study, we investigated protein Rv3261, isolated from an Mtb culture filtrate, for its apoptotic potential using multidimensional fractionation. Rv3261 was found to induce macrophage apoptosis through the caspase-3/-9-dependent pathway. Furthermore, the ROS-dependent JNK activation pathway was found to be critical in Rv3261-mediated apoptosis. Rv3261 inhibited the growth of intracellular Mtb, which was significantly abrogated by pre-treatment with the ROS scavenger N-acetylcysteine (NAC), suggesting that Rv3261-mediated apoptosis may act as a host defense response. These findings suggest that Rv3261 is involved in the apoptotic modulation of Mtb-infected macrophages.


Long lifetime and selective accumulation of the A-type lamins accounts for the tissue specificity of Hutchinson-Gilford progeria syndrome.
Mutations to the LMNA gene cause laminopathies including Hutchinson-Gilford progeria syndrome (HGPS) that severely affect the cardiovascular system. The origins of tissue specificity in these diseases are unclear, as the A-type Lamins are abundant and broadly expressed proteins. We show that A-type Lamin protein and transcript levels are uncorrelated across tissues. As protein-transcript discordance can be caused by variations in protein lifetime, we applied quantitative proteomics to profile protein turnover rates in healthy and progeroid tissues. We discover that tissue context and disease mutation each influence A-type Lamin protein lifetime. Lamin A/C has a weeks-long lifetime in the aorta, heart, and fat, where progeroid pathology is apparent, but a days-long lifetime in the liver and gastrointestinal tract, which are spared from disease. The A-type Lamins are insoluble and densely bundled in cardiovascular tissues, which may present an energetic barrier to degradation and promote long protein lifetime. Progerin is even more long-lived than Lamin A/C in the cardiovascular system and accumulates there over time. Progerin accumulation interferes broadly with protein homeostasis, as hundreds of abundant proteins turn over more slowly in progeroid tissues. These findings indicate that potential gene therapy interventions for HGPS will have significant latency and limited potency in disrupting the long-lived Progerin protein. Finally, we reveal that human disease alleles are significantly over-represented in the long-lived proteome, indicating that long protein lifetime may influence disease pathology and present a significant barrier to gene therapies for numerous human diseases.


Detection of subthreshold atrophy in crossed cerebellar degeneration via two-compartment mathematical modeling of cell density in DWI: A proof of concept study.
Crossed cerebellar diaschisis (CCD) refers to transneuronal degeneration of the corticopontocerebellar pathway, resulting in atrophy of cerebellum contralateral to supratentorial pathology. CCD is traditionally diagnosed on nuclear medicine studies. Our aim is to apply a biexponential diffusion model, composed of intracellular and extracellular compartments, to the detection of subthreshold CCD on DWI, with the calculated fraction of the intracellular compartment as a proposed measure of cell density. At a voxel-by-voxel basis, we solve for intracellular and extracellular coefficients in each side of the cerebellum and compare the distribution of coefficients between each hemisphere. We demonstrate, in all six CCD cases, a significantly lower contribution of the intracellular compartment to the cerebellar hemisphere contralateral to supratentorial pathology (p < 0.01). In a separate, proof-of-concept case of pontine stroke, we also demonstrate reduced intracellular coefficients in bilateral cerebellar hemispheres, excluding middle cerebellar peduncles (p < 0.01). Our findings are consistent with a decreased intracellular fraction, presumably a surrogate for reduced cellular density in corticopontocerebellar degeneration, despite normal-appearing scans. Our approach allows detection of subthreshold structural changes and offers the additional advantage of applicability to most clinical cases, where only three DWI beta values are available.